Homeostatic Mechanisms & Cellular Communication

Homeostasis
• Homeo means “the same”; stasis means “to stand or stay”.
• Maintenance of a relatively stable internal environment is termed as homeostasis.
Variables Homeostatically Regulated
1) Concentration of nutrients
2) Concentration of O2 and CO2
3) Concentration of waste products
4) pH
5) Concentration of water, salt, and other electrolytes
6) Volume and pressure
7) Temperature
Homeostatic Control Systems
A homeostatic control system is a functionally interconnected network of body components that
operate to maintain a given factor in the internal environment relatively constant around an optimal
level.
Steady State
• A system in which a particular variable is
not changing, but energy must be added
continuously to maintain a constant
condition.
• Equilibrium is a condition in which a
particular variable is not changing but no
input of energy is required to maintain the
constancy.
Characteristics of Control Systems
• The term feedforward is used for responses
made in expectation of a change.
• Feedback refers to responses made after a
change has been detected.

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Negative Feedback System
In this system, any change in the variable being regulated brings
about responses that tend to move the variable in the direction
opposite the direction of the original change.

Positive Feedback System

In this system, the output enhances or amplifies a change so that the controlled variable continues
to move in the direction of the initial change.

Components of Homeostatic Control Systems

Reflexes
Reflex is a specific involuntary, unpremeditated, unlearned “built-in” response to a particular
stimulus.
1. Stimulus
A stimulus is defined as a detectable change in the internal or external environment, such as a
change in temperature, plasma ionic concentration, or blood pressure.
2. Receptor
A receptor detects the environmental change.
3. Afferent Pathways
• Afferent means “to carry to,”.
• The pathway through which the signal travels between the receptor and the integrating
center is known as the afferent pathway.
4. Integrating Center
• A stimulus acts upon a receptor to produce a signal that is relayed to an integrating center.
• An integrating center often receives signals from many receptors, some of which may
respond to quite different types of stimuli.
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5. Efferent Pathway
• Efferent means “to carry away from,”.
• The pathway along which information,
from integrating center, travels is known as
the efferent pathway.
Effector
• The output of an integrating center is sent
to the last component of the system, whose
change in activity constitutes the overall
response of the system.
• This component is known as an effector.

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Local Homeostatic Responses
Local homeostatic responses are also stimulus-response sequences, but they occur only in the area
of the stimulus, with neither nerves nor hormones involved.
Intercellular Communication
• Intercellular communication can take place either directly or indirectly (chemically).
• Direct intercellular communication involves physical contact between the interacting cells:

Intercellular Chemical Messengers

• For homeostasis, communication between cells (intercellular communication) is performed
by chemical messengers.
• There are four categories of such messengers:
1) Hormones,
2) Neurotransmitters,
3) Paracrine and
4) Autocrine agents.

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1. Hormone
Hormone functions as a chemical messenger that enables the hormone-secreting cell to
communicate with cells acted upon by the hormone—its target cells—with the blood acting as the
delivery system.
2. Neurotransmitters
• One nerve cell alters the activity of another by releasing from its ending a neurotransmitter
that diffuses through the extracellular fluid and acts upon the second.
• Neurotransmitters released into the extracellular fluid in the immediate vicinity of effector
cells constitute the controlling input to the effector cells.
3. Paracrine Agents
• Chemical messengers involved in local communication between cells are known as
paracrine agents.
• Paracrine agents are synthesized by cells and released once given the appropriate stimulus,
into the extracellular fluid.
• They diffuse to neighboring cells, some of which are their target cells.
4. Autocrine Agents
• The chemical which is secreted by a cell into the extracellular fluid and then it acts upon
the same cell that secreted it.
• Such messengers are termed autocrine agents.

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 Processes Related to Homeostasis
Adaptation
• The term adaptation denotes a characteristic that favors survival in specific environments.
• Homeostatic control systems are inherited biological adaptations.
Acclimatization
• It is an improved ability of homeostatic control system to respond to an environmental
stress.
• The improvement is induced by prolonged exposure to the stress with no change in genetic
make up.
Developmental Acclimatization
If acclimatization occurs early in life, it may be irreversible and is known as a developmental
acclimatization.
Biological Rhythms
• The most common rhythm is the circadian rhythm, which cycles approximately once every
24 h.
• Biological rhythms provide a feedforward component to homeostatic control systems.

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 • The rhythms are internally driven by brain pacemakers, but are entrained by environmental
signals, such as light.
• The environmental signals also serve to phase-shift (reset) the rhythms when necessary.
Balance in the Homeostasis of Chemical Substances
• The balance of substances in the body is achieved by matching inputs and outputs.
• Total-body balance of a substance may be negative, positive, or stable.

Total-body Balance
Total-body balance of a substance may be;
1) Negative Balance: Loss exceeds gain, so that the total amount of the substance in the body
is decreasing.
2) Positive Balance: Gain exceeds loss, so that the total amount of the substance in the body
is increasing.
3) Stable Balance: Gain equals loss.

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 Receptors and Signal Transduction Pathways
Receptors
Receptors are proteins or glycoproteins located either in the plasma membrane or inside the cell
(sometimes), to which a chemical messenger binds and starts a biologically relevant response in
that cell.

Binding of Messenger with Receptor

• Chemical messenger is a ligand, and the receptor protein has a binding site for that ligand.
• The binding of a messenger by a receptor displays four characteristics.
1. Specificity,
2. Affinity,
3. Saturation, and
4. Competition.

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Competition
Competition is the ability of different messenger molecules that are very similar in structure to
compete with each other for a receptor.
Antagonist
• A molecule that competes for a receptor with a chemical messenger normally present in
the body.
• The antagonist binds to the receptor but does not trigger the cell’s response.
• Antihistamines are examples of antagonists.
Agonist
• A chemical messenger that binds to a receptor and triggers the cell’s response exactly as if
the true (endogenous) chemical messenger had combined with the receptor.
• Decongestants are examples of agonists.
Regulation of Receptors
The number of receptors a cell has, or the affinity of the receptors for their specific messenger, can
be increased or decreased in certain systems.
Down-regulation
• A decrease in the total number of target-cell receptors for a given messenger.
• It may occur in response to chronic high extracellular concentration of the messenger.
Up-regulation
• An increase in the total number of target cell receptors for a given messenger.
• It may occur in response to a chronic low extracellular concentration of the messenger.

Signal Transduction Pathways

Signal Transduction

The binding of a messenger to a receptor protein initiates a sequence of events in the cell leading
to the cell’s response to that messenger, the process called signal transduction.
Receptor Activation
• The combination of messenger with receptor causes a change in the conformation (three-
dimensional shape) of the receptor.
• This event is known as receptor activation.

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Responses
The responses of target cell can be changes in;
1) The permeability, transport properties, or electrical state of the plasma membrane;
2) The cell’s metabolism;
3) The cell’s secretory activity;
4) The cell’s rate of proliferation and differentiation; or
5) The cell’s contractile activity.
Signal Transduction Pathways
• The sequences of events between receptor activation and cellular responses are termed
signal transduction pathways.
• The “signal” is the receptor activation, and “transduction” denotes the process by which a
stimulus is transformed into a response.
Pathways Initiated by Lipid-Soluble Messengers
• Lipid-soluble messengers bind to receptors inside the target cell.
• The activated receptor acts in the nucleus as a transcription factor to alter the rate of
transcription of specific genes.
• This results in a change in the concentration or secretion of the proteins the genes encode.
Pathways Initiated by Water-Soluble Messengers
• Water-soluble messengers exert their actions on cells by binding to receptor proteins on
the extracellular surface of the plasma membrane.
• Water-soluble messengers include most hormones, neurotransmitters, and
paracrine/autocrine compounds.

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First Messengers
The intercellular chemical messengers that reach the cell from the extracellular fluid and bind to
their specific plasma membrane receptors are referred to as first messengers.
Second Messengers
• Second messengers are substances that enter or are generated in the cytoplasm as a result
of receptor activation by the first messenger.
• The second messengers diffuse throughout the cell to serve as chemical relays from the
plasma membrane to inside the cell.
1. Receptors that are Ligand-Gated Ion Channels
Activation of the receptor by a first messenger (the ligand) results in a conformational change of
the receptor such that it forms an open channel through the plasma membrane.
• They are particularly prevalent in the plasma membranes of nerve cells.

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2. Receptors that Function as Enzymes
• These receptors consist of an extracellular ligand-binding site.
• The intracellular site is enzymatic in nature (protein kinase or guanylyl cyclase).
Tyrosine Kinase Receptor
• The binding of a specific messenger to the receptor changes the conformation of the
receptor so that its enzymatic portion is activated.
• This results in phosphorylation of receptor’s own tyrosine groups.
• The newly created phosphor-tyrosines serve as docking sites for cytoplasmic proteins.
• The bound docking proteins then bind and activate other proteins, which activate one or
more signaling pathways within the cell.
• Most of the receptors with intrinsic tyrosine kinase activity influence cell proliferation and
differentiation.

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Guanylyl Cyclase Receptor
• Activation of these receptors leads to the formation of cyclic GMP (cGMP).
• cGMP functions as a second messenger to activate a protein kinase called cGMP-
dependent protein kinase.
• They are present in the retina and process visual inputs.
3. Receptors that Interact with Cytoplasmic JAK Kinases
• The binding of a first messenger to the receptor causes a conformational change in the
receptor that leads to activation of the JAK kinase.
• JAK kinases are family of separate cytoplasmic kinases which are associated with the
receptor.

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 • JAK kinases phosphorylate different target proteins, many of which act as transcription
factors.
• Signaling by cytokines (the immune system).
G-Protein-Coupled Receptors
The receptor is bound to a protein complex located on the cytosolic surface of the plasma
membrane and belonging to the family of heterotrimeric (containing three different subunits)
proteins known as G proteins.
• The G protein may cause the ion channel to open, with a resulting movement of ions.
• The G protein may activate or inhibit the membrane enzyme with which it interacts.
• Such enzymes, when activated, cause the generation of second messengers inside the cell.

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Families of G-Protein Coupled Receptors
Depending upon the second messenger, there are two categories of these receptors;
1) cAMP (Gs and Gi)
2) DAG and IP3 (Gq)
Gs and Gi
• The receptors are stimulatory, via a Gs protein, or inhibitory, via a Gi protein, to adenylyl
cyclase.
• The membrane effector enzyme adenylyl cyclase catalyzes the conversion of cytosolic
ATP to cyclic AMP.
• Cyclic AMP acts as a second messenger to activate intracellular cAMP dependent protein
kinase.
• This kinase phosphorylates proteins that mediate the cell’s ultimate responses to the first
messenger.

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Gq
• The receptor activate, via a Gq protein, the plasma membrane enzyme phospholipase C.
• This enzyme catalyzes the breakdown of a plasma membrane phospholipid known as
phosphatidylinositol bisphosphate (PIP2) to diacylglycerol (DAG) and inositol
trisphosphate (IP3).
• DAG activates protein kinase C which phosphorylate other proteins, leading to the cell’s
response.
• IP3 acts as a second messenger to release calcium from the endoplasmic reticulum.

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 Neural Control Mechanisms
Neural Tissue
• The nervous system is divided into two parts.
• The central nervous system (CNS) comprises the brain and spinal cord.
• The peripheral nervous system consists of nerves extending from the CNS.

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Structure and Maintenance of Neurons
• The basic unit of the nervous system is the nerve cell, or neuron.
• Neuron consists of following components;
1) Cell body contains the nucleus, ribosomes and other organelles
2) Dendrites are a series of highly branched outgrowths of the cell body.
3) The axon (nerve fiber) is a long structure that extends from the cell body and carries output
to its target cells.
The region where the axon connects to the cell body is known as the initial segment (axon hillock).
4) The axon may have branches, called collaterals.
5) Branches end in an axon terminal, which is responsible for releasing neurotransmitters.

Myelin
It consists of 20 to 200 layers of highly modified plasma membrane wrapped around the axon by
a nearby supporting cell.
• The myelin sheath speeds up conduction of the electrical signals along the axon and
conserves energy.

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 • In the CNS, the myelin-forming cells are the oligodendrocytes.
• In the peripheral nervous system, cells called Schwann cells form individual myelin sheaths
at regular intervals along the axons.
Nodes of Ranvier
The spaces between adjacent sections of myelin where the axon’s plasma membrane is exposed to
extracellular fluid are the nodes of Ranvier.

Axonal Transport
• Various organelles and other materials move between the cell body and the axon terminals
by axonal transport.

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 • The microtubules that extend from the beginning to the end of the axon provide a
“highway” for axonal transport.

Functional Classes of Neurons

Neurons can be divided into three functional classes:
1) Afferent neurons,
2) Efferent neurons, and
3) Interneurons.
I. AFFERENT NEURONS
• Transmit information into the CNS from receptors at their peripheral endings
• Cell body and the long portion of the axon are in the peripheral nervous system; only the
short portion of the axon enters the CNS.
• Most have no dendrites.

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II. EFFERENT NEURONS
• Transmit information out of the CNS to effector cells, particularly muscles, glands, or other
neurons.
• Cell body, dendrites, and a small segment of the axon are in the CNS; most of the axon is
in the peripheral nervous system.
III. INTERNEURONS
• Function as integrators and signal changers.
• Integrate groups of afferent and efferent neurons into reflex circuits.
• Lie entirely within the central nervous system.
• Account for 99 percent of all neurons.

Synapse
The anatomically specialized junction between two neurons where one neuron alters the electrical
and chemical activity of another is called a synapse.
• The neuron that conducts a signal toward a synapse is called a presynaptic neuron.
• The neuron conducting signals away from a synapse is a postsynaptic neuron.

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Glial Cells
• About 90% of the cells within the CNS are not neurons but glial cells or neuroglia.
• Glial cells serve as the connective tissue of the CNS and help support the neurons both
physically and metabolically.
Types of Glial Cells
There are four major types of glial cells in the CNS;
1) Astrocytes,
2) Oligodendrocytes,
3) Microglia, and
4) Ependymal cells.
1. Astrocytes
These are the most abundant glial cells. Their functions are;
1) Hold the neurons together in proper relationships.
2) Guides neurons to their proper final destination during fetal brain development.
3) Stimulate the formation of tight junctions between the endothelial cells of capillaries.
4) Help transfer nutrients to neurons.
5) Form neural scar tissue.
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 6) Take up and degrade released neurotransmitters.
7) Take up excess K+.
8) Enhance synapse formation and strengthen synaptic transmission.
9) Communicate by chemical means with neurons.
2. Oligodendrocytes
They form myelin sheaths in CNS.
3. Microglia
1) Play a role in defense of brain as phagocytic scavengers.
2) Release nerve growth factor.
4. Ependymal Cells
1) Line internal cavities of brain and spinal cord.
2) Contribute to formation of cerebrospinal fluid.
3) Serve as neural stem cells with the potential to form new neurons and glial cells.

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 Membrane Potentials
Basic Principles of Electricity
• Separated electrical charges of opposite sign have the potential called an electrical
potential. (table 6-3, Vander)
• It is determined by the difference in the amount of charge between two points called
potential difference.
• The movement of electrical charge is called a current.
Resting Membrane Potential (RMP)
All cells under resting conditions have a potential difference across their plasma membranes,
with the inside of the cell negatively charged with respect to the outside. This potential is the
resting membrane potential.
• The magnitude of the resting membrane potential varies from about –5 to –100 mV,
depending upon the type of cell.
• In neurons, it is generally in the range of –40 to –90 mV.
Generation of RMP
It is generated mainly by the diffusion of ions and are determined by;
1) The ionic concentration differences across the membrane, and
2) The membrane’s relative permeability to different ions.

• Plasma membrane Na+/K+-ATPase pumps maintain low intracellular sodium concentration

and high intracellular potassium concentration.
• Plasma membrane is much more permeable to potassium than to sodium, so the membrane
potential is close to the potassium equilibrium potential.
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Electrical Signals
• Transient changes in the membrane potential from its resting level produce electrical
signals.
• These signals occur in two forms;
1) Graded potentials and
2) Action potentials.
Terms for Electrical Signals
• Polarized means that the outside and inside of a cell have a different net charge. The
resting membrane potential, at –70 mV, is polarized.
• The membrane is depolarized when its potential becomes less negative (closer to zero)
than the resting level.
• Overshoot refers to a reversal of the membrane potential polarity i.e. when the inside of
a cell becomes positive relative to the outside.
• When a membrane potential that has been depolarized returns toward the resting value, it
is repolarizing.

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 • The membrane is hyperpolarized when the potential is more negative than the resting
level.

Graded Potentials
• Graded potentials are changes in membrane potential that are confined to a relatively
small region of the plasma membrane.
• These include receptor potential, synaptic potential, and pacemaker potential.

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Properties
1) Their amplitude varies with size of the initiating event.
2) These can be summed.
3) These have no threshold.
4) These have no refractory period.
5) These are conducted decrementally i.e. amplitude decreases with distance.
6) Their duration varies with initiating conditions.
7) These can be a depolarization or a hyperpolarization.
8) These are initiated by environmental stimulus (receptor), by neurotransmitter (synapse),
or spontaneously.
9) Their mechanism depends on ligand-gated channels or other chemical or physical
changes.

Action Potential
Action potentials are brief, rapid, large (100 mV) changes in membrane potential during which
the membrane rapidly depolarizes and repolarizes.
Voltage-Gated Ion Channels
• Voltage-gated membrane channels consist of proteins that have a number of charged
groups.

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 • The electrical field (potential) surrounding the channels can distort the channel structure
because of electrostatic forces.

Action Potential Mechanism

1) Steady resting membrane potential is -70 mV, PK > PNa, due to leak K+ channels.
2) Local membrane is brought to threshold voltage by a depolarizing stimulus.
At threshold, Na+ activation gate opens and PNa+ rises.
3) Na+ enters cell, causing explosive depolarization to +30 mV, which generates rising
phase of action potential.
4) At peak of action potential, Na+ inactivation gate closes and PNa+ falls, ending net
movement of Na+ into cell.
At the same time, K+ activation gate opens and PK+ rises.
5) K+ leaves cell, causing its repolarization to resting potential, which generates falling
phase of action potential.
6) On return to resting potential, Na+ activation gate closes and inactivation gate opens,
resetting channel to respond to another depolarizing triggering event.
7) Further outward movement of K+ through slow K+ channel briefly hyperpolarizes
membrane, which generates after hyperpolarization.
8) K+ activation gate closes, and membrane returns to resting potential.

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Positive Feedback Loop

Negative Feedback

Refractory Period
It is the time during which a new action potential cannot be initiated by normal events in a region
that has just undergone an action potential.
• It of two type; absolute refractory period and relative refractory period.
Absolute Refractory Period
During the time that a particular segment of axonal membrane is undergoing an action potential,
it cannot initiate another action potential, no matter how strong the depolarizing triggering event
is.

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Relative Refractory Period
It is the time during which a second action potential can be produced only by a triggering event
considerably stronger than usual.

Action Potential Propagation

• The transmembrane ionic currents produce local circuit currents around the axon.
• As a result of such localized changes in membrane potential, adjacent resting channels in
the axon are activated, and excitation of an adjacent portion of the axonal membrane
occurs.
• This brings about propagation of the action potential without decrement along the axon.
• The region that has undergone depolarization remains momentarily in a refractory state
so propagation will always be forward.

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Saltatory Conduction
In myelinated axon, the impulse “jumps” from node to node, skipping over the myelinated
sections of the axon; this process is called saltatory conduction.

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 Synapses and Neuronal Integration
Synapse
Synapse is an anatomically specialized junction between two neurons, at which the electrical
activity in a presynaptic neuron influences the electrical activity of a postsynaptic neuron.
Functional Types
1) An excitatory synapse brings the membrane of the postsynaptic cell closer to threshold.
2) An inhibitory synapse hyperpolarizes the postsynaptic cell or stabilizes it at its resting
level.
Convergence
When synapses from many different presynaptic cells can affect a single postsynaptic cell.
Divergence
When single presynaptic cell can send branches to affect many other postsynaptic cells.

Activity of Postsynaptic Cell

Whether a postsynaptic cell fires action potentials depends on the number of synapses that are
active and whether they are excitatory or inhibitory.
Functional Anatomy of Synapses
Anatomically, there are two types of synapses:
1) Electrical and
2) Chemical.

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Electrical Synapse
• At electrical synapses, the plasma membranes of the pre- and postsynaptic cells are joined
by gap junctions.
• These allow the local currents of action potentials to flow directly across the junction from
one neuron to the other.
Chemical Synapse
• The presynaptic neuron and the postsynaptic neuron are separated by a small gap — the
synaptic cleft.
• The synaptic cleft creates a physical barrier for the electrical signal.
• A chemical messenger links the action potential of one neuron with a synaptic potential in
another.
• The presynaptic neuron ends in a slight swelling which contains the synaptic vesicles that
contain the neurotransmitter.
• The postsynaptic membrane has a high density of membrane proteins that make up a
specialized area called the postsynaptic density.

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Mechanisms of Neurotransmitter Release
• Depolarization of the axon terminal by action potential causes opening of voltage gated
calcium channels.
• This raises the calcium concentration within the terminal, which causes the release of
neurotransmitter into the synaptic cleft.

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Effect of Calcium
• Calcium binds to vesicle proteins called synaptotagmins.
• This causes a conformational change in the SNARE complex that leads to the fusion of
vesicle and plasma membrane.
• SNARE stands for soluble N-ethylmaleimide-sensitive fusion protein attachment protein
receptors.

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Activation of the Postsynaptic Cell
• Neurotransmitters are released from the presynaptic axon terminal and bind to receptors on
the plasma membrane of the postsynaptic cell.
• The activated receptors may be ion channels, which designates them as ionotropic
receptors.
The receptors may act indirectly on separate ion channels through a G protein or a second
messenger, referred to as metabotropic receptors.
Synaptic Delay
The sequence of events involved between the arrival of an action potential at a presynaptic terminal
and the membrane potential changes in the postsynaptic cell, there is a very brief synaptic delay—
about 0.2 msec.
Excitatory Synapse
• The electrical response in the postsynaptic cell is called an excitatory postsynaptic potential
(EPSP).
• It is due to opening of channels in the postsynaptic cell that are permeable to sodium,
potassium, calcium and other small positive ions.

Inhibitory Synapse
• The electrical response in the postsynaptic cell is an inhibitory postsynaptic potential
(IPSP).
• It is due to opening of channels in the postsynaptic cell that are permeable to chloride
and/or potassium

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Fate of Neurotransmitter
Unbound neurotransmitters are removed from the synaptic cleft by;
1) Active transport back into the presynaptic axon terminal (reuptake) or into nearby glial
cells;
2) Diffuse away from the receptor site; or
3) Enzymatically transformed into inactive substances.
Synaptic Integration
The total potential in the postsynaptic neuron,
the grand postsynaptic potential (GPSP), is a
composite of all EPSPs and IPSPs occurring at
approximately the same time.

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Temporal Summation
The summing of several EPSPs occurring very close together in time because of successive firing
of a single presynaptic neuron is known as temporal summation.
Spatial Summation
The summation of EPSPs and IPSPs originating simultaneously from several different presynaptic
inputs (from different points in “space”) is known as spatial summation.
Synaptic Effectiveness
The effectiveness or strength of a
synapse is influenced by both
presynaptic and postsynaptic
mechanisms.

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 Modification of Synaptic Transmission by Drugs and Disease

1) Increase leakage of neurotransmitter from vesicle to cytoplasm,

2) Increase transmitter release into cleft,
3) Block transmitter release,
4) Inhibit transmitter synthesis
5) Block transmitter reuptake,
6) Block cleft enzymes that metabolize transmitter,
7) Bind to receptor on postsynaptic membrane (drugs only)
8) Inhibit or stimulate second-messenger activity within postsynaptic cell (drugs only).

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 Neurotransmitters and Neuromodulators
Neuromodulators
These are chemical messengers that do not cause the formation of EPSPs or IPSPs but rather bring
about long-term changes that modulate the action of the synapse.
Neurotransmitter
Neurotransmitters are molecules released by presynaptic neurons and are the means of
communication at a chemical synapse.
Acetylcholine
• Acetylcholine (ACh) is a major neurotransmitter in the peripheral nervous system at the
neuromuscular junction and in the brain.
• Neurons that release ACh are called cholinergic neurons.
• It is synthesized from choline and acetyl coenzyme A in the cytoplasm of synaptic
terminals.
• It is metabolized by the enzyme acetylcholinesterase present in synaptic cleft.
• There are two types of receptors for ACh:
1. The nicotinic receptors are ionotropic receptors and are coupled with a nonselective cation
channel.
2. The muscarinic receptors comprise a family of metabotropic receptors that are linked to G
protein–mediated pathways.
Biogenic Amines
• The biogenic amines are small, charged molecules that are synthesized from amino acids
and contain an amino group (R—NH2).
• The most common biogenic amines are catecholamines, serotonin, and histamine.
Catecholamines
• These contain a catechol ring (a six-carbon ring with two adjacent hydroxyl groups) and
an amine group.
• The catecholamines are formed from the amino acid tyrosine.
• The catecholamine neurotransmitters are metabolized by enzymes monoamine oxidase
(MAO).

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Norepinephrine
• Norepinephrine is a key neurotransmitter involved in wakefulness and attention.
• It acts on the metabotropic α-adrenergic and β-adrenergic receptors, both of which are
excitatory.
Dopamine
• Dopamine is involved in many forebrain circuits associated with emotion, motivation, and
reward.
• It acts on G protein–coupled receptors, and its action can be either excitatory (D1 receptors)
or inhibitory (D2 receptors).
Serotonin
• It is produced from tryptophan amino acid.
• It is involved in the regulation of mood, emotion, and several homeostatic pathways.
• There are 16 different receptor types for serotonin all of which are metabotropic and only
one receptor is ionotropic.
Histamine
• Histamine binds to an excitatory metabotropic receptor.
• In the CNS, it is involved in wakefulness.

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 Amino Acid Neurotransmitters
Glutamate
• Glutamate is the most common excitatory neurotransmitter in the CNS.
• Glutamate can bind to ionotropic receptors, which include NMDA receptors (N-methyl-D-
aspartate), AMPA receptors (α-amino-3-hydroxyl-5-methyl-4-isoxazole-propionate).
Long-term Potentiation
• It is a cooperative activity of AMPA and NMDA receptors.
• This mechanism links frequent activity across a synapse with long lasting changes in the
strength of signaling across that synapse.
• This is a cellular process underlying learning and memory.

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GABA
• GABA (gamma-aminobutyric acid) is the major inhibitory neurotransmitter in the brain.
• GABA can bind to ionotropic GABA receptors (GABAA and GABAC), which induce Cl−
influx.
• The metabotropic GABA receptor GABAB activates K+ channels and blocks Ca2+ channels.
Glycine
• It is the major inhibitory neurotransmitter in the spinal cord and brainstem.
• Glycine binds to an ionotropic receptor, which allows for Cl− influx.
• Balance of excitatory and inhibitory activity in spinal cord integrating centers that regulate
skeletal muscle contraction.
Neuropeptides
• The neuropeptides are composed of two or more amino acids linked together by peptide
bonds.
• They are synthesized in the neuronal cell body and are moved by axonal transport along
the microtubular highways to the axon terminal.
They include molecules involved in pain perception and modulation such as substance P,
metenkephalin, and opioids.
Miscellaneous
• Nitric oxide (NO) and carbon monoxide (CO) are produced by cytosolic enzymes.
• They diffuse into target’s intracellular fluid and activate guanylyl cyclase in the recipient
cell.
• This increases the concentration of the second-messenger cyclic GMP in that cell.
Neuroeffector Communication
• The junction between a neuron and an effector cell is called a neuroeffector junction.
• The events at a neuroeffector junction (release of neurotransmitter, diffusion of
neurotransmitter to effector cell, and binding with a receptor on the effector cell) are similar
to those at a synapse.

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 Central Nervous System
CNS (Brain)
• The CNS consists of the brain and spinal cord.
• There are estimated 100 billion neurons in the brain which are assembled into complex
networks.
General Functions
1) Subconsciously regulate internal environment by neural means,
2) Experience emotions,
3) Voluntarily control of movements,
4) Perceive (be consciously aware of) own body and surroundings, and
5) Engage in higher cognitive processes such as thought and memory.

Development of Brain

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Parts of the Brain
The order in which components are listed generally represents both their anatomic location (from
top to bottom) and their sophistication of function.
1) Forebrain
2) Brain stem
3) Cerebellum
Forebrain
1) Cerebrum
a. Cerebral cortex
b. Basal nuclei
2) Diencephalon
a. Thalamus
b. Hypothalamus
Brain Stem
• The brain stem is continuous with the spinal cord.
• It consists of;
1) The midbrain,
2) Pons, and
3) Medulla oblongata.

Forebrain
Cerebrum
• It is the largest portion of the human brain and is divided into two halves, the right and left
cerebral hemispheres.
• They are connected to each other by the corpus callosum which is a thick band consisting
of neuronal axons.
Cerebral Cortex
• The cerebral hemispheres consist of the cerebral cortex.
• The outer shell of gray matter composed primarily of cell bodies.
• The inner layer of white matter is composed primarily of myelinated fiber tracts.

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 • The folding in the cerebral cortex give characteristic external appearance with its sinuous
ridges called gyri.
• The gyri are separated by grooves called sulci.
Cortical Neurons
• The cortical neurons are of two basic types: pyramidal cells and non-pyramidal cells.
• The pyramidal cells form the major output cells of the cortex.
Lobes of Cerebral Cortex
The anatomic landmarks used in cortical mapping are specific deep folds that divide each half of
the cortex into four major lobes:
1) The occipital lobe,
2) Temporal lobe,
3) Parietal lobe, and
4) Frontal lobe.

• The occipital lobes is located posteriorly (at the back of the head), carry out the initial
processing of visual input.

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 • Auditory (sound) sensation is initially received by the temporal lobes which is located
laterally (on the sides of the head).
• The parietal lobes and frontal lobes, located on the top of the head, are separated by a deep
infolding, the central sulcus.
• The parietal lobes lie to the rear of the central sulcus on each side responsible for receiving
and processing sensory input.
The frontal lobes lie in front of central sulcus and are responsible for three main functions:
1) Voluntary motor activity,
2) Speaking ability, and
3) Elaboration of thought

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Basal Nuclei
• These subcortical nuclei are heterogeneous groups of gray matter that lie deep within the
cerebral hemispheres.
• These play an important role in controlling movement and posture and in more complex
aspects of behavior.
The Diencephalon
• It is the second component of the forebrain which is divided in two components by the
narrow third cerebral ventricle.
• It contains two major parts:
1) The thalamus and
2) The hypothalamus.
The Thalamus
• It is a collection of several large nuclei that serve as synaptic relay stations and important
integrating centers for most inputs to the cortex.
• It also plays a key role in general stimulation and focused attention.
The Hypothalamus
It is involved in;
1) Homeostatic regulation of the internal environment,
2) Modulation of pituitary gland function and
3) Control of behaviors which are important for preservation of the individual (eating and
drinking) and preservation of the species (reproduction).
The Limbic System
• Some of forebrain areas are also classified together in a functional system called the limbic
system.
• This interconnected group of brain structures includes portions of frontal lobe, temporal
lobe, thalamus, and hypothalamus.
• The limbic system is associated with learning, emotional experience and behavior, and a
wide variety of visceral and endocrine functions.

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Cerebellum
• The cerebellum consists of an outer layer of cells, the cerebellar cortex and several deeper
cell clusters.
• It is an important center for coordinating movements and for controlling posture and
balance.
Brain Stem
• The midbrain, pons, and medulla oblongata form the brainstem, which contains the
reticular formation.
• The reticular formation is involved in motor functions, cardiovascular and respiratory
control, and the mechanisms that regulate sleep and wakefulness and that focus attention.
Spinal Cord
• The spinal cord lies within the bony vertebral column.
• It is divided into two areas:
1) Central gray matter, which contains nerve cell bodies and dendrites; and

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 2) White matter, which surrounds the gray matter and contains myelinated axons.

3) The regions of gray matter projecting toward the back of the body are called the dorsal
horns.
4) The regions of gray matter oriented toward the front are the ventral horns.
Peripheral Nervous System
• The peripheral nervous system consists of 43 paired nerves.
• 12 pairs of cranial nerves (table 6-8 Vander) and 31 pairs of spinal nerves.
• The efferent division of the peripheral nervous system is divided into somatic and
autonomic parts.
The Somatic Portion
• The somatic portion consist of the nerve fibers going from the central nervous system to
skeletal muscle cells.
• The cell bodies of these neurons are located in groups in the brainstem or the ventral horn
of the spinal cord.
• Their large-diameter, myelinated axons leave the central nervous system and pass without
any synapses to skeletal muscle cells.
• The neurotransmitter these neurons release is acetylcholine.

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 • Somatic neurons causes contraction of the innervated skeletal muscle cells, so called as
motor neurons.
Autonomic Nervous System
• The autonomic nervous system innervates cardiac and smooth muscle, glands, and
gastrointestinal tract neurons.
• Each autonomic pathway consists of a preganglionic neuron with its cell body in the CNS
and a postganglionic neuron with its cell body in an autonomic ganglion outside the CNS.

• The autonomic nervous system is divided into sympathetic and parasympathetic

components.
• The preganglionic neurons in both the sympathetic and parasympathetic divisions release
acetylcholine.
• The postganglionic parasympathetic neurons release mainly acetylcholine; and the
postganglionic sympathetics release mainly norepinephrine.
• The adrenal medulla is a hormone-secreting part of the sympathetic nervous system and
secretes mainly epinephrine.
• Many effector organs that the autonomic nervous system innervates receive dual
innervation from the sympathetic and parasympathetic division of the autonomic nervous
system.

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 Protection and Nourishment of the Brain
Protection
Four features protect the CNS;
1) Hard, bony structures (cranium and the vertebral column)
2) The meninges.
3) The cerebrospinal fluid (CSF).
4) A highly selective blood–brain barrier.
Meningeal Membranes
• Three membranes, the meninges, wrap the CNS.
• From the outermost to the innermost layer they are;
1) The dura mater,
2) The arachnoid mater, and
3) The pia mater.
The Dura Mater
• The dura mater is a tough, inelastic covering that consists of two layers.
• They are separated to form blood filled cavities, dural sinuses or venous sinuses.
The Arachnoid Mater
• It is a delicate, richly vascularized layer with a weblike appearance.
• The space between the arachnoid layer and the underlying pia mater, the subarachnoid
space, is filled with CSF.
• Protrusions of arachnoid tissue, the arachnoid villi, penetrate through gaps in the overlying
dura.
The Pia Mater
• The innermost meningeal layer, the pia mater, is the most fragile.
• It is highly vascular and closely adheres to the surfaces of the brain and spinal cord.

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Cerebrospinal Fluid (CSF)
• Cerebrospinal fluid (CSF) surrounds and cushions the brain and spinal cord.
• The major function of CSF is to serve as a shock-absorbing fluid and exchange of materials
between the neural cells.
Formation of CSF
• Cerebrospinal fluid is formed primarily by the choroid plexuses found in particular regions
of the ventricles.
• Choroid plexuses consist of richly vascularized masses of pia mater tissue that dip into
pockets formed by ependymal cells.
• Cerebrospinal fluid forms as a result of selective transport mechanisms across the
membranes of the choroid plexuses.
• CSF contains less K- and slightly higher Na+ and almost no plasma proteins.
Flow of CSF
1) CSF circulates throughout the ventricles.
2) It exits the fourth ventricle at the base of the brain.

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3) Then flows in the subarachnoid space between the meningeal layers, and
4) It is finally reabsorbed from the subarachnoid space into the venous blood across the
arachnoid villi.

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Blood–brain Barrier (BBB)
• The blood-brain barrier closely regulates the chemical composition of the extracellular
fluid of the CNS.
• The BBB has both anatomic and physiologic features.
Anatomic Feature
In brain capillaries, the cells are joined by tight junctions, which completely seal the capillary wall
thus preventing the para-cellular transport.
Physiologic Feature
• Lipid-soluble substances penetrate CNS easily by dissolving in their lipid plasma
membrane.
• Water molecules also diffuse through readily through aquaporins.
• All water soluble substances are transported in CNS by highly selective membrane-bound
carriers.
Role of Astrocytes in BBB
• They signal the endothelial cells forming the brain capillaries to “get tight.”
• They participate in the cross-cellular transport of some substances, such as K-.

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 Sensory Physiology
Sensory System
A sensory system is a part of the nervous system that consists of sensory receptor cells (receive
stimuli), the neural pathways (conduct information), and parts of the brain (processing the
information).
Sensory Information
• Information that a sensory system processes is called sensory information.
• If the information reaches consciousness, it is called a sensation.
• A person’s understanding of the sensation’s meaning is called perception.
Sensory Receptors
Sensory receptors translate information from the external and internal environments into graded
potentials, which then generate action potentials.
• The receptors are either specialized endings of afferent neurons or,
• They may be separate cells that signal the afferent neurons by releasing chemical
messengers.

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Sensory Transduction
• The process by which a stimulus is transformed into an electrical response is known as
sensory transduction.
• The energy or chemical that affects and activates a sensory receptor is known as a stimulus.
• The type of stimulus to which a particular receptor responds in normal functioning is
known as its adequate stimulus.
Types
• Mechanoreceptors respond to mechanical stimuli e.g. pressure or stretch.
• Thermoreceptors detect both sensations of cold and warmth, and photoreceptors respond
to particular light wavelengths.
• Chemoreceptors respond to the binding of particular chemicals to the receptor membrane.
• Nociceptors are specialized nerve endings that respond to a number of different painful
stimuli.
Receptor Potential
• The transduction process in all sensory receptors involves the opening or closing of ion
channels.
• The gating of ion channels allows a change in the ion fluxes across the receptor membrane,
which in turn produces a change in the membrane potential which is a graded potential
called a receptor potential.
Generation of Action Potential
The specialized receptor membrane region where the initial ion channels cause local current to
flow a short distance along the axon to a region where the membrane has voltage-gated ion
channels and can generate action potentials.

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 • If the receptor membrane is on a separate cell, the receptor potential alters the release of
neurotransmitter from that cell.
• The neurotransmitter binds with its binding sites generates a graded potential in the afferent
neuron like an excitatory postsynaptic potential.
Factors of Receptor Potential
Receptor potential magnitude varies with;
1) Stimulus strength,
2) Rate of change of stimulus application,
3) Temporal summation of successive receptor potentials, and
4) Adaptation.
Adaptation
It is a decrease in receptor sensitivity, which results in a decrease in action potential frequency in
an afferent neuron despite a stimulus of constant strength.

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Primary Sensory Coding
• Converting stimulus energy into a signal that conveys the relevant sensory information to
the central nervous system is termed coding.
• Coding begins at the receptive neurons in the peripheral nervous system.
• A single afferent neuron with all its receptor endings makes up a sensory unit.
• The area of the body that, when stimulated, leads to activity in a particular afferent neuron
is called the receptive field for that neuron.

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 Components of Sensory Coding
1. Stimulus Type
• The type of stimulus perceived is determined by the type of receptor activated.
• All receptors of a given sensory unit respond to the same stimulus modality (type).
2. Stimulus Intensity
Stimulus intensity is coded by;
1) The rate of firing of individual sensory units and,
2) The number of sensory units activated.

3. Stimulus Location
Perception of the stimulus location depends on;
1) The size of the receptive field covered by a single sensory unit and
2) The overlap of nearby receptive fields.

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Area of Receptive Field
• An afferent neuron responds most vigorously to stimuli applied at the center of its receptive
field because the receptor density is greatest there.
• The response decreases as the stimulus is moved toward the receptive field periphery.

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Lateral Inhibition
• Lateral inhibition is a means by which ascending pathways increase sensory acuity.
• In lateral inhibition, information from afferent neurons whose receptors are at the edge of
a stimulus is strongly inhibited compared to information from the stimulus’s center.

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4. Stimulus Duration
Stimulus duration is coded by the type of receptor;
1) Rapidly adapting receptors respond very rapidly at the stimulus onset but stop firing
during the remainder of the stimulus.
2) Slowly adapting receptors maintain their response at or near the initial level of firing
regardless of the stimulus duration.

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Central Control of Afferent Information
Information coming into the nervous system is controlled by;
1) Inhibition from collaterals from other ascending neurons (lateral inhibition).
2) The reticular formation and cerebral cortex via descending pathways.

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Neural Pathways in Sensory Systems
• A bundle of parallel, three-neuron chains together form a sensory pathway.
• The chains in pathway run parallel to each other in the central nervous system and carry
information to the cerebral cortex.
Ascending Pathways
• Sensory pathways are also called ascending pathways because they go “up” to the brain.
• The afferent neurons enter the brain or spinal cord and synapse upon interneurons there.
• The interneurons upon which the afferent neurons synapse are termed second-order
neurons and so on.
1. The Specific Ascending Pathways
• The ascending pathways that carry information about single types of stimuli are known as
the specific ascending pathways.
• The specific ascending pathways pass to the brainstem and thalamus, and the final neurons
in the pathways go to specific sensory areas of the cerebral cortex.

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2. The Nonspecific Ascending Pathways
• Neurons in the nonspecific ascending pathways are activated by sensory units of several
different types and signal general information.
• Such pathway neurons are called polymodal neurons.
Association Cortex
• The cortical association areas are brain areas that lie outside the primary cortical sensory
or motor areas but are adjacent to them.
• They are not part of the sensory pathways, but they play a role in the progressively more
complex analysis of incoming information.

Perceptual Processing
Information from the primary sensory cortical areas is elaborated after it is relayed to a cortical
association area.
Simple Processing
When the primary sensory cortical area and the region of association cortex closest to it process
the information in simple ways and serve basic sensory-related functions.

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Complex Processing
• When regions of association cortex farther from the primary sensory areas process the
sensory information in more complicated ways.
• Complex processing in the association cortex includes input from areas of the brain serving
other sensory system, arousal, attention, memory, language, and emotions.
Factors that Affect Perception
1) Sensory receptor mechanisms and processing of the information along afferent pathways.
2) Factors such as emotions, personality, experience, and social background.
3) Damaged neural networks may give faulty perceptions.
4) Some drugs alter perceptions.

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 Specific Sensory Systems
Somatic Sensation
• Sensation from the skin, muscles, bones, tendons, and joints is known as somatic sensation.
• The somatic sensations include touch, pressure, the senses of posture and movement,
temperature, and pain.
• It is initiated by a variety of sensory receptors collectively called somatic receptors.
Somatic Receptors in Skin
A. Meissner's corpuscle—rapidly adapting mechanoreceptor (touch and pressure).
B. Merkle's corpuscle—slowly adapting mechanoreceptor (touch and pressure).
C. Free nerve ending—slowly adapting nociceptors, thermoreceptors, and mechanoreceptors.
D. Pacinian corpuscles—rapidly adapting mechanoreceptor (vibration and deep pressure).
E. Ruffini corpuscle—slowly adapting mechanoreceptor (skin stretch).

Touch and Pressure

Rapidly adapting mechanoreceptors of the skin give rise to sensations such as vibration, touch,
and movement, whereas slowly adapting ones give rise to the sensation of pressure.

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 • Skin receptors with small receptive fields are involved in fine spatial discrimination,
• Receptors with larger receptive fields signal less spatially precise touch-pressure
sensations.
Sense of Posture and Movement
A major receptor type responsible for the senses of posture and movement in joints (kinesthesia)
is the muscle spindle stretch receptor.
Temperature
Two types of thermoreceptors respond to temperature in the skin.
1) Cold-sensing receptors have nonselective cation (Na+) channels that open in response to
temperatures (35oC-0oC).
2) Warmth-sensing thermoreceptors are activated (30oC-50oC) and nonselective cation
channels depolarize the cell.
Pain
• Tissue damage and immune cells release chemical agents that stimulate specific receptors
that give rise to the sensation of pain.
• Nociceptors are pain sensitive receptors and respond to intense mechanical deformation,
excessive heat, and many chemicals.

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Referred Pain
When incoming nociceptive afferents activate interneurons and the sensation of pain is
experienced at a site other than the injured or diseased tissue e.g. heart attack is accompanied by
pain in the left arm.

Modification of Pain Stimuli

After transduction of the first noxious stimuli into action potentials in the afferent neuron, a series
of changes occur in the pain pathway that alter response to subsequent stimuli.
1) When changes in pain pathway result in an increased sensitivity to painful stimuli, it is
known as hyperalgesia.
2) Analgesia is the selective suppression of pain without effects on consciousness or other
sensations.
1. Stimulation-produced Analgesia
Electrical stimulation of specific areas of the central nervous system can produce a profound
reduction in pain by inhibiting pain pathways.

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2. Acupuncture
• An ancient Chinese therapy involving the insertion of needles into specific locations on
the skin.
• It activates afferent neurons leading to spinal cord and midbrain centers that release
endogenous opioids.
3. Transcutaneous Electric Nerve Stimulation (TENS)
• The painful site itself or the nerves leading from it are stimulated by electrodes placed on
the surface of the skin.
• TENS works because the stimulation of nonpain, low-threshold afferent fibers leads to the
inhibition of neurons in the pain pathways.
Mechanism of Pain Inhibition

Neural Pathways of the Somatosensory System

• The afferent nerve fibers form the specific ascending pathways going primarily to the
somatosensory cortex via the brainstem and thalamus.

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 • There are two major somatosensory pathways.
1. The Ascending Anterolateral Pathway
• It is also called the spinothalamic pathway.
• It makes first synapse between the sensory receptor neuron and a second neuron located in
the gray matter of the spinal cord.
• The second neuron crosses the opposite side and projects through the anterolateral column
of the cord to the thalamus.
• The second neuron then synapses in this pathway is on cortically projecting neurons.
• The anterolateral pathway processes pain and temperature information.
2. The Dorsal Column Pathway
• It makes first synapse between the sensory receptor neuron and a second neuron located in
the brain stem nucleus.
• The second neuron then synapses in this pathway is on cortically projecting neurons.
• This pathway processes body movement, limb positions, fine touch discrimination, and
pressure.

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Somatosensory Cortex
• Each region within the somatosensory cortex receives somatosensory input from a specific
area of the body.
• The distribution of cortical sensory processing is described in sensory homunculus.

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 • The somatosensory cortex on each side of the brain receives sensory input from the
opposite side of the body.

Vision
• The eyes capture the patterns of illumination in the environment as an “optical picture” on
a layer of light-sensitive cells, the retina.
• The eyes are composed of an optical portion and a neural component.
Eye Anatomy
• Eye is a spherical, fluid-filled structure enclosed by three layers.
• From outermost to innermost, these are;
1) The sclera/cornea;
2) The choroid/ciliary body/iris; and

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 3) The retina
1. The Sclera/Cornea
• The sclera is a tough outer layer of connective tissue, forms the visible white part of the
eye.
• Anteriorly, the outer layer consists of the transparent cornea.
2. The Choroid/Ciliary body/Iris
• The middle layer underneath the sclera is the highly pigmented choroid which absorb light
rays at the back of the eyeball.
• In the front the choroid layer is specialized into the iris (associated with eye color).
• The ciliary muscle and the zonular fibers determines the shape of crystalline lens.
• The pupil is the anterior opening that allows light into the eye.
• Circular and radial smooth muscle fibers of the iris determine the diameter of pupil.
3. The Retina
• The retina is an extension of the brain lining the inner, posterior surface of the eye.
• The retina contains;
1) The fovea centralis (deliver the highest visual acuity);
2) The optic disc (neurons from the photoreceptors)
3) Blood vessels (inner surface of the retina).

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The Vitreous Humor
• The cavity between the lens and retina contains a semifluid, jellylike substance called the
vitreous humor.
• The vitreous humor helps maintain the spherical shape of the eyeball.
The Aqueous Humor
• The cavity between the cornea and lens contains a clear, watery fluid called the aqueous
humor.
• The aqueous humor carries nutrients for the cornea and lens.
The Optics of Vision
• The light that falls on the retina is focused by the cornea and lens by refraction.
• Lens shape changes (accommodation) permit viewing near or distant objects so that they
are focused on the retina.
Control of Shape of Lens
• The shape of the lens is controlled by the ciliary muscle and the zonular fibers.
• The ciliary muscle is circular like sphincter, stimulated by parasympathetic nerves.
• When this muscle contracts, it draws nearer to the central lens.
Control of Amount of Light
• Stimulation of sympathetic nerves to the iris enlarges the pupil by causing radially arranged
muscle fibers to contract.
• Stimulation of parasympathetic fibers to the iris makes the pupil smaller because of
contraction of circular muscles, which circle around the pupil.
Photoreceptor Cells
• Photoreceptors are rod and cone cells.
• These consist of three parts;
1) An outer segment which detects the light stimulus.
2) An inner segment which contains the metabolic machinery of the cell.
3) A synaptic terminal which transmits the signal generated in the photoreceptor.

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Photopigment
• The outer segment of photoreceptor consists of stacked, flattened, membranous discs
containing an abundance of light-sensitive photopigment molecules.
• There are four unique photopigments in the retina, one found in rods (rhodopsin), and one
in each of three different types of cones.

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A photopigment consists of two components:
1. Opsin is an integral protein in the disc plasma membrane; and
2. Retinal, a derivative of vitamin A, is the light-absorbing part of the photopigment.
Phototransduction
• The photoreceptor is depolarized at rest, and hyperpolarized in response to stimulus.
• In the absence of light, guanylyl cyclase converts GTP into a cyclic GMP (cGMP).
• The cGMP maintains the ligand gated cation channels in the open state, and a persistent
influx of sodium and calcium results.
• When light falls upon the retinal, the photic energy causes the retinal to change shape.
• This stimulates an interaction between associated opsins and transducin which is a
member of the G-protein family.
• Transducin activates phosphodiesterase which rapidly degrades cGMP.
• The decrease in cytoplasmic cGMP concentration allows the cation channels to close
allows the membrane potential to hyperpolarize.

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Neural Pathways of Vision
• Light signals are converted into action potentials through the interaction of photoreceptors
with bipolar cells and ganglion cells.
• Photoreceptor and bipolar cells only undergo graded responses; ganglion cells are the first
cells in the pathway where action potentials can be initiated.

• Photoreceptors are depolarized in the absence of light, causing the neurotransmitter

glutamate to be released onto bipolar cells.
• Photoreceptors interact with bipolar and ganglion cells in two distinct ways, designated as
“ON-pathways” and “OFF-pathways.”

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On-pathway Bipolar Cells
• Glutamate released onto ON-pathway bipolar cells binds to metabotropic receptors that
cause breakdown of cGMP which hyperpolarizes the bipolar cells.
• Bipolar cells are prevented from releasing excitatory neurotransmitter onto their associated
ganglion cells.
• When light strikes the photoreceptors, glutamate release from photoreceptors decreases.
• ON-bipolar cells depolarize, excitatory neurotransmitter is released, the ganglion cells are
depolarized, and action potentials propagate to the brain.
Off-pathway Bipolar Cells
• OFF-pathway bipolar cells have ionotropic glutamate receptors that depolarize the bipolar
cells when glutamate binds.
• Depolarization of these bipolar cells stimulates them to release excitatory neurotransmitter
onto their associated ganglion cells, stimulating them to fire action potentials.
• Thus, the OFF-pathway generates action potentials in the absence of light.
• When light strikes the photoreceptors, glutamate release from photoreceptors decreases.
• OFF-bipolar cells hyperpolarize, excitatory neurotransmitter is not released, the ganglion
cells are hyperpolarized, and action potentials are inhibited.
Importance of On & Off Pathway
The co-existence of ON and OFF pathways in each region of the retina greatly improves image
resolution by increasing the brain’s ability to perceive contrast at edges or borders.

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Pathway in the Brain

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 • The axons of the ganglion cells form the output from the retina—the optic nerve, which is
cranial nerve II.
• The optic nerve fibers from the medial half of each retina cross to the opposite side of the
brain in the optic chiasm.
The fibers from the optic nerves terminate in the lateral geniculate nuclei of the thalamus, which
send fibers to the visual cortex.

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 Ear: Hearing and Equilibrium
Ear
Ear consists of three parts:
1) The external ear transmit airborne sound waves to the middle ear.
2) The middle portion of the ear amplify sound energy and transmit to the inner ear.
3) The inner ear contains two different sensory systems:
I. The cochlea (convert of sound waves into nerve impulses)
II. The vestibular apparatus (necessary for the sense of equilibrium).

Properties of Sound
• Sound energy is transmitted by movements of pressure waves.
• Sound wave frequency determines pitch.
• Sound wave amplitude determines loudness.

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 • The timbre (quality) of a sound depends on overtones (frequencies superimposed).

Hearing
• Hearing is the neural perception of sound energy.
• It involves two aspects:
1) Identification of the sounds (“what”) and
2) Their localization (“where”).

Sound Transmission in the Ear

The External Ear
• The external ear consists of the pinna (ear), external auditory meatus (ear canal), and
tympanic membrane (eardrum).
• Sound waves enter the external auditory meatus and press against the tympanic membrane,
causing it to vibrate.
Middle Ear
• It is an air-filled cavity in the temporal bone of the skull.
• The pressure in this cavity is equal to atmospheric pressure because of eustachian tube,
which connects the middle ear to the pharynx.

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 • The middle ear transfers the vibratory movements of the tympanic membrane to the fluid
of the inner ear.
• The vibrating tympanic membrane causes movement of the three small middle-ear bones
(ossicular system)
• The malleus (attached to the tympanic membrane)
• The incus (middle bone)
• The stapes (attached to the oval window).
The Oval Window
• It is a membrane-covered entrance into the fluid-filled cochlea, separating the middle and
inner ears.
• The ossicular system amplifies the pressure of the airborne sound waves to set up fluid
vibrations in the fluid of cochlea.
Inner Ear
• The pea-sized, snail-shaped cochlea, the “hearing” portion of the inner ear, is a coiled
tubular system.
• The cochlea is divided into three fluid-filled longitudinal compartments.
1) A blind-ended cochlear duct (the scala media), constitutes the middle compartment.
2) The upper compartment (the scala vestibule), and
3) The lower compartment (the scala tympani).
• The fluid within the scala vestibuli and scala tympani is called perilymph.
• The cochlear duct contains a slightly different fluid, the endolymph.
• The region beyond the tip of the cochlear duct where the fluid in the upper and lower
compartments is continuous is called the helicotrema.
• The vestibular membrane separates the scala vestibule from cochlear duct.
• The basilar membrane forms the floor of the cochlear duct, separating it from the scala
tympani.
• The basilar membrane contains the organ of Corti, the sense organ for hearing.

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The organ of Corti
• The organ of Corti contains auditory hair cells that are the receptors for sound.
• The hair cells are mechanoreceptors that have hair like stereocilia.
• The stereocilia of the hair cells are in contact with the tectorial membrane, which overlies
the organ of Corti.
• The stereocilia of each hair cell are organized into rows of graded heights ranging from
short to tall in a precise staircase pattern.
• Tip links (cell adhesion molecules) link the tips of stereocilia in adjacent rows.

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Transmission of Sound
• Movements of the oval window membrane set up pressure waves in the fluid-filled scala
vestibule.
• This cause vibrations in the cochlear duct wall, setting up pressure waves in the endolymph.
• These pressure waves cause vibrations in the basilar membrane, which is located on one
side of the cochlear duct.
• As this membrane vibrates, the hair cells of the organ of Corti move in relation to the
tectorial membrane.

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Sound Transduction
• When the stereocilia are bent toward the tallest member of a bundle tip links pull open
mechanically gated cation channels.
• The result is cation influx which depolarizes the membrane.
• This opens voltage-gated calcium channels at the base of cell, which triggers glutamte
release.
• Bending the hair cells in the opposite direction slackens the tip links, closing the channels
and allowing the cell to rapidly repolarize.
• Thus, as sound waves vibrate the basilar membrane, the stereocilia are bent back and forth,
the membrane potential of the hair cells rapidly oscillates, and bursts of neurotransmitter
are released onto afferent neurons.

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Neural Pathways in Hearing
• Sound signal are transmitted to brain by the cochlear branch of the vestibulocochlear nerve
(cranial nerve VIII).
• Cochlear nerve fibers enter the brainstem and synapse with interneurons there.
• From the brainstem, the information is transmitted to the thalamus and on to the auditory
cortex in the temporal lobe.
• The neurons responding to different frequencies are arranged along the auditory cortex in
an orderly manner.
• Different areas of the auditory system are further specialized; some neurons respond to
complex sounds (used in verbal communication).

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 • Other areas process the location, movement, duration, or loudness of a sound.
Vestibular System
• The vestibular system detects changes in position and motion of the head.
• It consists of two sets of structures lying within the temporal bone near the cochlea;
1) The semicircular canals and
2) The otolith organs.

Semicircular Canals
• Each ear contains three semicircular canals arranged three-dimensionally in planes that lie
at right angles to each other.
• The receptor hair cells of each semicircular canal are situated on top of a edge located in
the ampulla, a swelling at the base of the canal.
• The hairs are embedded in an overlying, caplike, gelatinous layer, the cupula, which
protrudes into the endolymph within the ampulla.
• The semicircular canals detect angular acceleration during rotation of the head, which
causes bending of the stereocilia on their hair cells.

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Otolith Organs
• The otolith organs, the utricle and the saccule, are saclike structures situated between the
semicircular canals and the cochlea.
• The hairs of the receptor hair cells in these sense organs protrude into an overlying
gelatinous sheet.
• Crystals of calcium carbonate (the otoliths) are suspended within the gelatinous layer,
making it heavier than the surrounding fluid.
• Otoliths move in response to changes in linear acceleration and the position of the head
relative to gravity, and stimulate the stereocilia on the hair cells.

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Vestibular Information
Vestibular information is used in three ways;
1) Control the eye muscles so that the eyes can remain fixed on the same point.
2) Reflex mechanisms for maintaining upright posture and balance.
3) Providing conscious awareness of the position and acceleration of the body.
Neural Pathway
• Information about hair cell stimulation is relayed from the vestibular apparatus to nuclei
within the brainstem via the vestibular branch of the vestibulocochlear nerve.
• It is transmitted via a multineuronal pathway through the thalamus to a system of vestibular
centers in the parietal lobe.
• Descending projections are also sent from the brainstem nuclei to the spinal cord to
influence postural reflexes.

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• Vestibular information is integrated with information from the joints, tendons, and skin,
leading to the sense of posture (proprioception) and movement.

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 Chemical Senses: Taste and Smell
Chemical Senses
• Chemical senses generate neural signals on binding with particular chemicals in their
environment.
• The chemical senses provide a “quality-control” checkpoint for substances available for
ingestion.
• These senses include taste (gustation) and smell (olfaction).
Taste
• The chemoreceptors for taste sensation are packaged in taste buds, which are present in the
oral cavity and throat.
• A taste bud consists of about 50 long, spindle-shaped taste receptor cells packaged with
supporting cells.
• Each taste bud has a small opening,
the taste pore, through which fluids
in the mouth come into contact with
the surface of its receptor cells.
• Small, hair like projections increase
the surface area of taste receptor
cells, and contain integral
membrane proteins for
transduction.
At the bottom of taste buds are basal cells,
which divide and differentiate to
continually replace taste receptor cells
damaged in the harsh environment of the
mouth.

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Types of Taste Receptors
Taste types generally fall into five different categories;
1) Sweet,
2) Sour,
3) Salty,
4) Bitter, and
5) Umami.

Taste Transduction
Salty Taste
• Salty taste is stimulated by chemical salts, especially NaCl.
• Direct entry of Na+ ions through specialized Na+ channels is responsible for receptor cell
depolarization in response to salt.
Sour Taste
• Sour taste is stimulated by foods with high acid content, such as lemons.
• Depolarization of the receptor cell occurs because H+ blocks K+ channels in the receptor
cell membrane.
• The resultant decrease in the efflux of K+ ions reduces the hyperpolarization.
Sweet Taste
• Sweet receptors bind natural sugars (glucose) and artificial sweetener (saccharin).
• Binding of sugars to these receptors activates a G-protein-coupled second-messenger
pathway.
• This ultimately blocks potassium channels and thus generates a depolarizing receptor
potential.
Bitter Taste
• Bitter flavor is associated with many poisonous substances (strychnine and arsenic).
• Each receptor cell has a diverse family of bitter receptors to respond a wide variety of
unrelated chemicals.
• All of these types generate receptor potentials via G-protein-mediated second-messenger
pathways.

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Umami Taste
• This taste is triggered by amino acids, especially glutamate and give the sense of
flavorfulness.
• Glutamate binds to a G protein–coupled receptor and activates a second-messenger
pathway.
Neural Pathways
• Afferent endings of several cranial nerves synapse with taste buds in various regions of the
mouth.
• Signals in these sensory inputs are conveyed via synaptic stops in the brain stem and
thalamus.
Neurons form thalamus project to the cortical gustatory area lie in the parietal lobe adjacent to
the “tongue” area of the somatosensory cortex.
Smell
• The flavor of food is actually contributed by the sense of smell, or olfaction.
• The olfactory (smell) mucosa is epithelial patch of in the roof of the nasal cavity, contains
three cell types.

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Olfactory Mucosa
1) The supporting cells secrete mucus.
2) The basal cells are precursors for new olfactory receptor cells, which are replaced about
every two months.
3) An olfactory receptor cell is an afferent neuron whose receptor portion lies in the olfactory
mucosa in the nose and afferent axon traverses into the brain.

Smell Transduction
• Binding of an appropriate scent signal to an olfactory receptor activates a G protein.
• G protein triggers a cascade of cAMP dependent intracellular reactions that leads to
opening of cAMP-gated nonspecific cation channels.
The resultant net Na+ entry causes a depolarizing receptor potential that generates action
potentials in the afferent fiber.

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Neural Pathway
• The afferent fibers from the receptor in the nose pass through tiny holes in the flat bone
plate separating the olfactory mucosa from the overlying brain tissue.
• The axons of the neurons form the olfactory nerve (cranial nerve I).
• These axons immediately synapse in the olfactory bulb.

Olfactory Bulb
• It is a complex neural structure containing several different layers of cells.
• Each olfactory bulb is lined by small ball-like neural junctions known as glomeruli.
• Within each glomerulus, the terminals of receptor cells synapse with the next cells in the
olfactory pathway, the mitral cells.

• The mitral cells refine the smell signals and relay them to the brain.
• Fibers leaving the olfactory bulb travel in two different routes:
1) A subcortical route going primarily to the limbic system (the primary olfactory cortex).
2) A route through the thalamus to the cortex.

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 Principles of Hormonal Control Systems
The Endocrine System
• The endocrine system is one of the body’s two major communications systems.
• It consists of all the endocrine glands that secrete hormones.
• Hormones are chemical messengers the blood carries from the endocrine glands to target
cells elsewhere in the body.
Hormone Structures and Synthesis
Hormones fall into three major chemical classes:
1) Amines,
2) Peptides and proteins, and
3) Steroids.
Amine Hormones
• The amine hormones are all derivatives of the amino acid tyrosine.
• They include;
1) The thyroid hormones (thyroid gland),
2) The catecholamines; epinephrine and norepinephrine (adrenal medulla), and
3) Dopamine (hypothalamus).

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Peptide and Protein Hormones
• Most hormone are small peptides having only three amino acids to small proteins.
• Peptide hormones are synthesized on the ribosomes as larger proteins known as
preprohormones.
• Preprohormone are cleaved to prohormones by proteolytic enzymes in the rough
endoplasmic reticulum.
• The prohormone is cleaved to yield the active hormone and other peptide chains.
• Both of these are packaged into secretory vesicles by the Golgi apparatus.

Steroid Hormones
• Steroid hormones are produced from cholesterol by the adrenal cortex and the gonads, and
by the placenta during pregnancy.

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 • The ovaries produce mainly estradiol and progesterone, and the testes mainly testosterone.
• The steroid hormones produced by the adrenal cortex are;
• The mineralocorticoid aldosterone,
• The glucocorticoid cortisol,
• Two androgens i.e. dehydroepiandrosterone and androstenedione.
Synthesis
1) The gland cells are stimulated by the binding of a pituitary gland hormone to its receptor.
2) These receptors are linked to G-proteins, which activate adenylyl cyclase and thus cAMP.
3) The subsequent activation of protein kinase A results in phosphorylation of membrane
proteins.
4) The cholesterol is stored in an esterified form in large, non-membrane-bound lipid droplets.
5) Protein kinase A activate cholesterol esterase which releases free cholesterol from lipid
droplet.
6) Carrier proteins then transport the free cholesterol to the mitochondria.
7) Inner mitochondrial membrane contains cytochrome P450s which are required to process
cholesterol into steroid hormones.
8) As the P450 enzymes modify cholesterol intermediates, they are modified before the final
steroid hormone is produced.
9) These modifications involve the enzymatic reactions in mitochondria and smooth
endoplasmic reticulum.
10) After synthesis they diffuse out into the interstitial fluid and from there into the circulation.
11) Steroid hormones are not highly soluble in blood, and thus transported in plasma bound to
carrier proteins such as albumin.

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Hormone Transport in the Blood
• Peptide hormones and catecholamines are water soluble so they circulate dissolved in the
plasma.
• Steroid and thyroid hormones circulate mainly bound to plasma proteins.
• The total hormone concentration in plasma is the sum of the free and bound hormones.
• The free hormone can diffuse out of capillaries and encounter its target cells, hence this
concentration is biologically important.
Hormone Metabolism and Excretion
• The liver and kidneys are the major organs that remove hormones from the plasma by
metabolizing or excreting them.
• The peptide hormones and catecholamines are rapidly removed from the blood.
• The steroid and thyroid hormones are removed more slowly because they circulate bound
to plasma proteins.
• Some hormones are metabolized to more active molecules in their target cells or other
organs e.g. testosterone, which is converted either to estradiol or dihydrotestosterone.

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Mechanisms of Hormone Action
• The majority of receptors for steroid and thyroid hormones are inside the target cells.
• The receptors for the peptide hormones and catecholamines are on the plasma membrane.
Signal Transduction of Hormones
• Receptors activated by peptide hormones and catecholamines utilize one or more of the
signal transduction pathways.
• The result is altered membrane potential or protein activity in the cell.
• In some cases, the signal transduction pathways also lead to activation or inhibition of
particular genes.
• Intracellular receptors activated by steroid and thyroid hormones function as transcription
factors.
• The activated receptors combine with DNA in the nucleus and inducing the transcription
of DNA into mRNA.

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 Inputs that Control Hormone Secretion
The secretion of a hormone are controlled by;
1) The plasma concentration of an ion or nutrient that the hormone regulates.
2) Neural input to the endocrine cells, and
3) One or more hormones.

Control by Ions or Organic Nutrients

• This control system works on the principle of negative feedback mechanism.
• As insulin secretion is stimulated by an increase in plasma glucose and inhibited by
decreased glucose level.
• Regulation of Ca2+ homeostasis by parathyroid hormone (PTH).

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Control by Neurons

Control by Other Hormones

• The secretion of some hormones is directly controlled by the blood concentration of
another hormone.
• A hormone that stimulates the secretion of another hormone is often referred to as a tropic
hormone.
Types of Endocrine Disorders
Endocrine disorders may be classified as;
1) Hyposecretion,
2) Hypersecretion, and
3) Target-cell hypo- or
4) Hyperresponsiveness.

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1. Hyposecretion
• If endocrine gland secretes too little hormone due to gland damage, the condition is termed
primary hyposecretion.
• Secondary hyposecretion is the condition in which the endocrine gland is not damaged
initially, but is receiving too little of its tropic hormones.
2. Hypersecretion
• Primary hypersecretion is the condition in which the gland is secreting too much of the
hormone on its own.
• Secondary hypersecretion is the condition in which excessive stimulation of the gland
occur by its tropic hormone.
3. Hyporesponsiveness
Hyporesponsiveness is due to;
1) Alteration in the receptors for the hormone,
2) Disordered post-receptor events,
3) Failure of normal metabolic activation of the hormone.
4. Hyperresponsiveness
• Hyperresponsiveness to a hormone occur by up-regulation of certain receptors.
• As hypersecretion of thyroid hormone causes hyperresponsiveness to epinephrine.

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 Control Systems Involving the Hypothalamus and Pituitary
The Pituitary Gland
• The pituitary gland (hypophysis) lies in a pocket (sella turcica) of the sphenoid bone just
below the hypothalamus.
• The pituitary gland is connected to the hypothalamus by the infundibulum, a stalk
containing nerve fibers and small blood vessels.
• The pituitary gland is composed of two adjacent lobes;
• The anterior pituitary (adenohypophysis) arises embryologically from an invagination of
the pharynx called Rathke’s pouch
• The posterior pituitary (neurohypophysis), an extension of the neural components of the
hypothalamus.

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Posterior Pituitary Hormones
• The hormones are not synthesized in the posterior pituitary but in the hypothalamus, the
cell bodies of the supraoptic and paraventricular nuclei.
• The hormone moves down the axons to accumulate at the axon terminals in the posterior
pituitary.

1. Vasopressin
Vasopressin (antidiuretic hormone, ADH) has two major effects:
1) It enhances retention of H2O by the kidney nephrons during urine formation,
2) It causes contraction of arteriolar smooth muscles.
Oxytocin
1) It stimulates contraction of the uterine smooth muscle to help expel the infant during
childbirth, and
2) It promotes ejection of the milk from the mammary glands (breasts) during breast-feeding.

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Anterior Pituitary Hormones
The anterior pituitary secretes;
1) Growth hormone (GH),
2) Thyroid-stimulating hormone (TSH),
3) Adrenocorticotropic hormone (ACTH),
4) Prolactin, and
5) Two gonadotropic hormones—follicle-stimulating hormone (FSH) and luteinizing
hormone (LH).

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Hypophysiotropic Hormones
• The hypothalamic hormones that regulate anterior pituitary function are collectively
termed hypophysiotropic hormones.
• They are also commonly called hypothalamic releasing or inhibiting hormones.

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Control of Hypophysiotropic Hormones
The secretion of each hypophysiotropic hormone is controlled by
1) Neuronal and
2) Hormonal
input to the hypothalamic neurons producing specific hormone.

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Long-loop Negative Feedback
In the three-hormone sequences beginning with a hypophysiotropic hormone, the third hormone
exerts negative feedback effects on the secretion of the hypothalamic and/or anterior pituitary
hormone.
The Thyroid Gland
• The thyroid gland consists of two lobes of endocrine tissue joined by the isthmus.
• The major thyroid secretory cells are the follicular cells which secrete thyroxine (T4) and
triiodothyronine (T3).
• The C cells secrete the peptide hormone calcitonin.

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The Follicle
• Follicular cells are arranged into hollow spheres, each of which forms a functional unit
called a follicle.
• The follicles are filled with protein-rich material called the colloid.
• The colloid contains a glycoprotein molecule known as thyroglobulin (Tg).
Synthesis of Thyroid Hormones
• Tyrosine-containing thyroglobulin produced within the thyroid follicular cells is
transported by exocytosis into the colloid.
• Iodide is carried by secondary active transport from the blood into the colloid by
symporters in the basolateral membrane of the follicular cells (iodide trapping).
• In the follicular cell, the iodide is oxidized to active form by thyroid peroxidase at the
luminal membrane.
• The active iodide exits the cell through a luminal channel to enter the colloid.
• Thyroid peroxidase attaches one iodide to tyrosine of the thyroglobulin molecule to
produce monoiodotyrosine (MIT).
• Attachment of two iodides to tyrosine yields diiodotyrosine (DIT).
• The phenolic ring of a molecule of MIT or DIT is removed from the remainder of its
tyrosine and coupled to another DIT on the thyroglobulin molecule.
• Coupling of one MIT and one DIT yields T3 while coupling of two DITs yields T4.
• On appropriate stimulation, the thyroid follicular cells engulf thyroglobulin by
phagocytosis.
• Lysosomes attack the engulfed vesicle and split the iodinated products from thyroglobulin.
• T3 and T4 diffuse into the blood (secretion).
• MIT and DIT are deiodinated, and the freed iodide is recycled for synthesizing more
hormone.

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Control of Thyroid Function
• All of the synthetic steps involved in T3/T4 synthesis are stimulated by TSH.
• TSH also stimulates uptake of iodide, where it is trapped in the follicle.
• TSH causes growth of thyroid tissue.
• Excessive exposure of the thyroid to TSH can cause goiter.

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Actions of Thyroid Hormones
• The actions of T3 and T4 are widespread and affect many organs and tissues.
• The receptors are located in the nucleus and can bind both T3 and T4, but have a much
higher affinity for T3.
• Generally there are three type of effects of thyroid hormones.
Metabolic Actions
• Thyroid hormones stimulate carbohydrate absorption from the small intestine and increases
fatty acid release from adipocytes.
• Thyroid hormones stimulate the activity of Na+/K+ -ATPases throughout the body.
• Ultimately increase the metabolic rate, and thus promote consumption of calories
(calorigenic effect).
Permissive Actions
• Thyroid hormones up-regulate beta-adrenergic receptors in many tissues, notably the heart
and nervous system.
• The actions of the sympathetic nervous system are potentiated by T3/T4.

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 • This is called the permissive action of T3/T4.

Growth and Development

• Thyroid hormones are essential for normal growth and development, particularly of the
nervous system, during fetal life and childhood.
• Absence of thyroid hormones during fetal life results in a poorly developed nervous system
and a form of mental retardation called cretinism.

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 The Endocrine Response to Stress
Cortisol
• Cortisol is released from the adrenal cortex upon stimulation with ACTH.
• ACTH is stimulated by the release of corticotropin-releasing hormone (CRH) from the
hypothalamus.
Physiological Functions of Cortisol
Generally there are four type of effects of cortisol in the body.
1) Metabolic Effects.
2) Permissive Actions.
3) Anti-inflammatory and Immunosuppressive Effects.
4) Growth and Development.
1. Metabolic Effects
• It stimulates hepatic gluconeogenesis.
• It inhibits glucose uptake and use by many tissues and spare it for use by the brain.
• It stimulates protein degradation in many tissues, especially muscle.
• It facilitates lipolysis in adipose tissue and increases free fatty acids into the blood.
2. Permissive Effects
Cortisol must be present in adequate amounts to permit the catecholamines to induce
vasoconstriction.
3. Anti-inflammatory and Immunosuppressive Effects
• Cortisol inhibits the production both leukotrienes and prostaglandins.
• Cortisol also stabilizes lysosomal membranes in damaged cells.
• It reduces capillary permeability in injured areas, thus reducing fluid leakage to the
interstitium.
• It suppresses the growth and function of certain key immune cells.
4. Growth and Development
• During fetal and neonatal life, cortisol is also an extremely important developmental
hormone.
• It is required for the proper differentiation of the brain, the adrenal medulla, the intestine
and the lungs.

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Functions of Cortisol in Stress
• The stimulus that activates the CRH/ACTH/cortisol endocrine pathway is stress.
• In response to stress, the usual physiological functions of cortisol are enhanced as cortisol
levels in the plasma increase.
• This results in increased blood levels of fuel sources (glucose, fatty acids).

Other Hormones Released During Stress

• Beta-endorphin is coreleased with ACTH and may act to reduce pain.
• Vasopressin stimulates ACTH secretion and also acts on the kidney to increase water
retention.
• Epinephrine is secreted from the adrenal medulla during stress, in response to stimulation
from the sympathetic nervous system.

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 Endocrine Control of Growth
Bone Growth
• Bone is a living tissue consisting of an extracellular organic (collagen) matrix known as
osteoid.
• The bone cells that produce the collagen are known as osteoblasts (bone formers).
• Bone is made hard by precipitation of calcium phosphate crystals within the osteoid.
• Cartilage is similar to bone, except that living cartilage is not calcified.
• A long bone consists of a uniform cylindrical shaft called the diaphysis.
• The wide articulating knob at both ends is called an epiphysis.
• In a growing bone, the diaphysis is separated at each end from the epiphysis by a layer of
cartilage known as the epiphyseal plate.

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 • A bone lengthens as osteoblasts at the shaft edge of the epiphyseal growth plates convert
cartilage to bone while new cartilage is being laid down in the plates by chondrocytes.
• Growth ceases when the plates are completely converted to bone, this is known as
epiphyseal closure.
Environmental Factors Influencing Growth
• The major environmental factors influencing growth are nutrition and disease.
• Maternal malnutrition during pregnancy may produce irreversible growth stunting and
mental deficiency in offspring.
Hormonal Influences on Growth
• The hormones involved in growth are growth hormone, insulin-like growth factors I and
II, thyroid hormones, insulin, testosterone, and estrogens.
• A large group of peptide growth factors exert effects as paracrine and autocrine agents.
• The general term for a chemical that stimulates cell division is a mitogen.
Growth Hormone and Insulin-Like Growth Factors
• Growth hormone is the major stimulus of postnatal growth.
• Growth hormone exerts its mitogenic effect indirectly through the mediation of a mitogen
e.g. IGF-1.
• Growth hormone stimulates IGF-1 secretion by the liver, enters the blood, and functions
as a hormone.
• Growth hormone also stimulates many other types of cells to secrete IGF-1, and at these
sites IGF-1 functions as an autocrine or paracrine agent.
Effect on Bone
• Growth hormone stimulates the prechondrocytes and young differentiating chondrocytes
in the epiphyseal plates to differentiate into chondrocytes;
• During this differentiation, the cells begin both to secrete IGF-1 and to become responsive
to IGF-1;
• The IGF-1 then acts as an autocrine or paracrine agent, along with blood-borne IGF-1, to
stimulate the differentiating chondrocytes to undergo cell division.
Thyroid Hormones
• Thyroid hormones are required for growth hormone synthesis and the growth-promoting
effects of this hormone hence they are essential for normal growth during childhood and
adolescence.

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 • They are also permissive for brain development during infancy.

Insulin
• Insulin is an anabolic hormone that promotes the entry of glucose and amino acids from
the extracellular fluid into cells.
• Insulin stimulates storage of fat and inhibits protein degradation.
• Insulin exerts direct growth-promoting effects on cell differentiation and cell division
during fetal life.
Sex Hormones
• Testosterone and estrogen promote bone growth during adolescence.
• The major growth promoting effect of the sex hormones is to stimulate the secretion of
growth hormone and IGF-1.
• These hormones also cause epiphyseal closure.

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 Endocrine Control of Ca2+ Homeostasis
Role of Calcium
1. Neuromuscular excitability.
2. Excitation–contraction coupling in cardiac and smooth muscle.
3. Stimulus–secretion coupling.
4. Excitation–secretion coupling.
5. Maintenance of tight junctions between cells.
6. Clotting of blood.
Calcium Homeostasis
• Calcium homeostasis depends on interchange among bone, the kidneys, and the
gastrointestinal tract.
• The gastrointestinal tract and kidneys determine the net intake and output of calcium for
the entire body.
• Exchange of calcium between extracellular fluid and bone affect the distribution of calcium
within the body.
Bone
• Approximately 99 percent of total-body calcium is contained in bone.
• The flux of calcium into and out of bone is vital in controlling plasma calcium
concentration.

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Structure
• Bone is a special connective tissue made up of several cell types surrounded by a collagen
matrix, called osteoid.
• Minerals are deposited in osteoid, particularly the crystals of calcium and phosphate known
as hydroxyapatite.
Cells of Bone
The three types of bone cells involved in bone formation and breakdown are;
1) Osteoblasts,
2) Osteocytes, and
3) Osteoclasts.
1. Osteoblasts
• Osteoblasts are the bone-forming cells.
• They secrete collagen to form a surrounding matrix, which then becomes calcified
(mineralization).
2. Osteocytes
• When osteoblasts are surrounded by calcified matrix, they are called osteocytes.
• The osteocytes have long cytoplasmic extensions that extend throughout the bone and form
tight junctions with other osteocytes.
3. Osteoclasts
• Osteoclasts are large, multinucleated cells that break down (resorb) previously formed
bone.
• They secrete hydrogen ions, which dissolve the crystals, and hydrolytic enzymes, which
digest the osteoid.
Bone Remodeling
• Bone deposition (formation) and bone resorption (removal) normally go on concurrently,
this is called as bone remodeling.
• Osteoclasts resorb old bone, and then osteoblasts move into the area and lay down new
matrix, which becomes mineralized.

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Kidney
• The urinary excretion of calcium is the difference between the amount filtered and the
amount reabsorbed.
• The control of calcium excretion is exerted through hormones mainly on reabsorption.
• Reabsorption decreases when plasma calcium concentration increases, and increases when
plasma calcium decreases.
Gastrointestinal Tract
Calcium is actively absorbed by the gastrointestinal tract, and this process is under hormonal
control.
Hormonal Controls
The three major hormones that regulate plasma calcium concentration are;
1) Parathyroid hormone,
2) 1,25-dihydroxyvitamin D and
3) Calcitonin.
Parathyroid Hormone
• Parathyroid hormone (PTH) is a peptide hormone secreted by the parathyroid glands.
• Parathyroid hormone production is controlled by the extracellular calcium concentration.

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 • Parathyroid hormone increases plasma calcium concentration by influencing all of the
effector sites.
Effects of Parathyroid Hormone
Parathyroid hormone stimulates;
1) Kidney reabsorption of calcium,
2) Bone resorption with release of calcium into the blood, and
3) Formation of 1,25-dihydroxyvitamin D, which stimulates calcium absorption by the
intestine.
It also inhibits the reabsorption of phosphate in the kidneys, leading to increased excretion of
phosphate in the urine.

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1,25-dihydroxyvitamin D
• Vitamin D denotes a group of closely related compounds.
• Vitamin D3 (cholecalciferol) is formed by sunlight in skin.
• Vitamin D2 (ergocalciferol) is derived from plants.
• 1,25-dihydroxyvitamin D (1,25-(OH)2D, also called calcitriol), the active form of vitamin
D.
• Vitamin D is metabolized by the addition of hydroxyl groups, first in the liver by the
enzyme 25-hydroxylase and then in kidney by 1-hydroxylase.
• Parathyroid hormone stimulates 1-hydroxylase.
Effects of 1,25-dihydroxyvitamin D
1) The major action of 1,25-(OH)2D is to stimulate the intestinal absorption of calcium.
2) It also increases intestinal PO43+ absorption.
3) It increases the responsiveness of bone to PTH.

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Calcitonin
• Calcitonin is a peptide hormone secreted by called parafollicular cells (C cells) of thyroid
gland.
• Calcitonin decreases plasma calcium concentration, mainly by inhibiting osteoclasts,
thereby reducing bone resorption.
• Its secretion is stimulated by an increased plasma calcium concentration.

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 Muscle Physiology
Muscle
There are three types of muscle;
1) Skeletal muscle is attached to bones and moves and supports the skeleton.
2) Smooth muscle surrounds hollow cavities and tubes.
3) Cardiac muscle is the muscle of the heart.

Structure of Skeletal Muscle

• A single skeletal muscle cell is known as a muscle fiber.
• Muscle fiber is formed by the fusion of a number of undifferentiated, mononucleated cells,
known as myoblasts, into a single cylindrical, multinucleated cell.
• Skeletal muscles are attached to bones by bundles of collagen fibers known as tendons.
• The striated pattern in skeletal muscle results from the arrangement of numerous thick and
thin filaments in the cytoplasm into myofibrils.
• The thick and thin filaments in each myofibril are arranged in a repeating pattern along the
length of the myofibril, known as a sarcomere.

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• The thick filaments are composed almost entirely of the protein myosin.
• The thin filaments are principally composed of the protein actin and two other proteins—
troponin and tropomyosin.
• The thick filaments are located in the middle of each sarcomere produces a wide, dark band
known as the A band.
• A light band known as the I band lies between the ends of the A bands of two adjacent
sarcomeres.
• One end of each thin filament is anchored to a network of interconnecting proteins known
as the Z line.
• The H zone is a narrow, light band in the center of the A band.
• A narrow, dark band in the center of the H zone is known as the M line.
• The elastic protein titin extend from the Z line to the M line and are linked to both the M-
line proteins and the thick filaments.

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Cross-bridges
• The space between overlapping thick and thin filaments is bridged by projections known
as cross-bridges.
• These are portions of myosin molecules that extend from the surface of the thick filaments
toward the thin filaments.

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Molecular Mechanisms of Skeletal Muscle Contraction
When a skeletal muscle fiber actively shortens, the thin filaments are propelled toward the center
of their sarcomere by movements of the myosin cross-bridges that bind to actin.

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Actin Filament
• An actin molecule is a globular protein composed of a single polypeptide that polymerizes
with other actins to form two intertwined, helical chains.
• These chains make up the core of a thin filament.
• Each actin molecule contains a binding site for myosin.
Myosin Filament
• The myosin molecule is composed of two large polypeptide heavy chains and four smaller
light chains.
• These polypeptides combine to form a molecule that consists of two globular heads and a
long tail.
• Each globular head contains two binding sites, one for actin and one for ATP.

Cross-bridge Cycle
The sequence of events that occurs between the time a cross-bridge binds to a thin filament, moves,
and then is set to repeat the process is known as a cross-bridge cycle.
• Each cycle consists of four steps;

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 1. Attachment of the Cross-bridge to Thin Filament
• Cross-bridge cycling is initiated when calcium enters the cytoplasm.
• The cycle begins with the binding of an energized myosin cross-bridge to a thin filament
actin molecule.

2. Movement of the Cross-bridge

• The binding of energized myosin to actin triggers the
release of the strained conformation of the energized
bridge.
• This produces the movement of the bound cross-bridge
called the power stroke and the release of Pi and ADP.

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 3. Detachment of Cross-bridge from Thin Filament
• During the cross-bridge movement, myosin is bound very firmly to actin.
• This linkage must be broken to allow the cross-bridge to be re-energized and repeat the cycle.
• The binding of a new molecule of ATP to myosin breaks the link between actin and myosin.

4. Energizing the Cross-bridge

• Following the dissociation of actin and
myosin, the ATP bound to myosin is split.
• Thereby re-forming the energized state of
myosin and returning the cross-bridge to its
prepower-stroke position.

Role of ATP
• The energy released from ATP hydrolysis ultimately provides the energy for cross-bridge
movement.
• ATP binding to myosin breaks the link formed between actin and myosin during the cycle,
allowing the cycle to repeat.
Roles of Tropomyosin
• Chains of tropomyosin molecules are arranged end to end along the actin thin filament.

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 • These tropomyosin molecules partially cover the myosin-binding site on each actin
molecule and prevent the cross-bridges from making contact with actin.
Role of Troponin
• Troponin interacts with both actin and tropomyosin.
• Troponin binds to tropomyosin and regulates the access to myosin-binding sites on the
actin molecules.
• This is the status of a resting muscle fiber; troponin and tropomyosin cooperatively block
the interaction of cross-bridges with the thin filament.
Role of Calcium
• When calcium binds to specific binding sites on the troponin.
• The shape of troponin changes, which relaxes its inhibitory grip.
• This allows tropomyosin to move away from the myosin binding site on each actin
molecule.

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Excitation-Contraction Coupling
Excitation-contraction coupling refers to the sequence of events by which an action potential in
the plasma membrane of a muscle fiber leads to the cross-bridge activity.
• The electrical activity in the plasma membrane produces a state of increased cytosolic
calcium concentration.
• This calcium continues to activate the contractile apparatus long after the electrical activity
in the membrane has ceased.
• The source of the increased cytosolic calcium is the sarcoplasmic reticulum within the
muscle fiber.

Sarcoplasmic Reticulum
• The sarcoplasmic reticulum in muscle is the endoplasmic reticulum.
• This structure forms a series of sleeve-like segments around each myofibril.
• At the end of each segment are two enlarged regions, known as lateral sacs, that are
connected to each other by a series of smaller tubular elements.

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• A separate tubular structure, the transverse tubule (T-tubule), lies directly between the
lateral sacs of adjacent segments of the sarcoplasmic reticulum.
• The T-tubules are in contact with the lateral sacs of the sarcoplasmic reticulum, connected
by structures known as junctional feet.
• This junction involves two integral membrane proteins.
• The T-tubule protein is a modified voltage-sensitive calcium channel known as the
dihydropyridine (DHP) receptor.
• The protein embedded in the sarcoplasmic reticulum membrane is known as the ryanodine
receptor.

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Mechanism
• The action potential is propagated into the interior of the fiber along the transverse tubules
to the region of the sarcoplasmic reticulum.
• Dihydropyridine receptors sense the voltage change and pull open ryanodine receptors,
releasing calcium ions from the reticulum.
• The calcium ions bind to troponin, producing a change in its shape to uncover the binding
sites on actin, allowing the cross-bridges to bind to the thin filaments.
• Relaxation of a contracting muscle fiber occurs as a result of the active transport of
cytosolic calcium ions back into the sarcoplasmic reticulum.

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The Neuromuscular Junction
• The junction of an axon terminal with the motor end plate is known as a neuromuscular
junction.
• The region of the muscle fiber plasma membrane that lies directly under the terminal
portion of the axon is known as the motor end plate.
Mechanism of Membrane Excitation
1) Action potential is initiated and propagates to motor neuron axon terminals.
2) Calcium enters axon terminals through voltage-gated calcium channels.
3) Calcium entry triggers release of ACh from axon terminals.
4) ACh diffuses from axon terminals to motor end plate in muscle fiber.
5) ACh binds to nicotinic receptors on motor end plate, increasing their permeability to Na+
and K+.
6) More Na+ moves into the fiber at the motor end plate than K+ moves out, depolarizing the
membrane and producing the end plate potential (EPP).
7) Local currents depolarize the adjacent muscle cell plasma membrane to its threshold
potential.
8) This generates an action potential that propagates over the muscle fiber surface and into
the fiber along the T-tubules.
9) The neuromuscular junction contains the enzyme acetylcholinesterase, which breaks down
Ach.
A single action potential in a motor neuron is sufficient to produce an action potential in a skeletal
muscle fiber.

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Mechanics of Single-Fiber Contraction
• The force exerted on an object by a contracting muscle is known as muscle tension.
• The force exerted on the muscle by an object (usually its weight) is the load.
• Contraction refers to the turning on of the cross-bridge cycle.
Types of Contractions
Three types of contractions can occur following activation of a muscle fiber:
1) An isometric contraction in which the muscle generates tension but does not change
length;
2) An isotonic contraction in which the muscle shortens (concentric), moving a load;
3) Lengthening (eccentric) contraction in which the external load on the muscle causes the
muscle to lengthen during the period of contractile activity.
Twitch Contractions
• The mechanical response of a muscle fiber to a single action potential is known as a twitch.
• Latent period is the time interval before the tension in the muscle fiber begins to increase.
• The time interval from the beginning of tension development at the end of the latent period
to the peak tension is the contraction time.
Load-Velocity Relation
• The velocity of muscle fiber shortening decreases with increases in load.
• Maximum velocity occurs at zero load.
Frequency-Tension Relation
• Increasing the frequency of action potentials in a muscle fiber increases the mechanical
response (tension or shortening).
• The increase in muscle tension from successive action potentials occurring during the
phase of mechanical activity is known as summation.
• A maintained contraction in response to repetitive stimulation is known as a tetanus
(tetanic contraction).
Length-Tension Relation
• The length at which the fiber develops the greatest isometric active tension is termed the
optimal length, L0.
• Stretching a fiber beyond its optimal length or decreasing the fiber length below L0
decreases the tension generated.

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Skeletal Muscle Energy Metabolism
There are three ways a muscle fiber can form ATP:
1) Phosphorylation of ADP by creatine phosphate,
2) Oxidative phosphorylation of ADP, and
3) Phosphorylation of ADP by the glycolytic pathway in the cytosol.

Source of Fuel
• At the beginning of exercise, muscle glycogen is the major fuel consumed.
• As the exercise proceeds, glucose and fatty acids from the blood provide most of the fuel.
• Fatty acids become progressively more important during prolonged exercise.
When the intensity of exercise exceeds about 70 percent of maximum, glycolysis begins to
contribute an increasing fraction of the total ATP generated.
Muscle Fatigue
• When a skeletal muscle fiber is repeatedly stimulated, the tension the fiber develops
eventually decreases even though the stimulation continues.

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 • This decline in muscle tension as a result of previous contractile activity is known as
muscle fatigue.
Factors of Fatigue
A variety of factors cause muscle fatigue including;
1) Internal changes in acidity,
2) Cross-bridge inhibition,
3) Glycogen depletion, and
4) Excitation-contraction coupling failure,
But lack of ATP is not the reason.
Types of Skeletal Muscle Fibers
Three types of skeletal muscle fibers can be distinguished by;
1) Their maximal shortening velocities and
2) The predominate pathway they use to form ATP.
3) Slow-oxidative fibers (Type I) combine low myosin ATPase activity with high oxidative
capacity.
4) Fast-oxidative-glycolytic fibers (Type IIa) combine high myosin-ATPase activity with
high oxidative capacity and intermediate glycolytic capacity.
5) Fast-glycolytic fibers (Type IIb) combine high myosin-ATPase activity with high
glycolytic capacity.
Differences
• Differences in maximal shortening velocities are due to different myosin enzymes with
high or low ATPase activities, giving rise to fast and slow fibers.
• Fast-glycolytic fibers have a larger average diameter than oxidative fibers and therefore
produce greater tension, but they also fatigue more rapidly.
Whole-Muscle Contraction
• The nerve cells whose axons innervate skeletal muscle fibers are known as motor neurons.
• A motor neuron plus the muscle fibers it innervates is called a motor unit.

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Effect of Motor Unit and Muscle Type
• Muscles that produce delicate movements have a small number of fibers per motor unit.
• Large powerful muscles have much larger motor units.
• Fast-glycolytic motor units not only have large-diameter fibers but also tend to have large
numbers of fibers per motor unit.
Control of Muscle Tension
The tension produced by whole-muscle contraction depends on;
1) The amount of tension each fiber develops and
2) The number of active fibers in the muscle.

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 • Increases in muscle tension are controlled primarily by increasing the number of active
motor units in a muscle, a process known as recruitment.
• Slow-oxidative motor units are recruited first during weak contractions, then fast-oxidative
glycolytic motor units, and finally fast-glycolytic motor units during very strong
contractions.
Control of Shortening Velocity
Increasing motor-unit recruitment increases the velocity at which a muscle will move a given load.
Muscle Adaptation to Exercise
Exercise can alter a muscle’s strength and susceptibility to fatigue.
1) Long-duration, low-intensity exercise increases a fiber’s capacity for oxidative ATP
production by increasing the number of mitochondria and blood vessels in the muscle,
resulting in increased endurance.
2) Short-duration, high-intensity exercise increases fiber diameter as a result of increased
synthesis of actin and myosin, resulting in increased strength.
Movement of Muscles Around Joints
• Flexion refers to the bending of a limb at a joint, whereas extension is the straightening of
a limb.
• Groups of muscles that produce oppositely directed movements at a joint are known as
antagonists.
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Movement around a joint requires two antagonistic groups of muscles:
1) One flexes the limb at the joint and
2) The other extends the limb.

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 Control of Body Movement
Motor Neuron Pool
• All the motor neurons that supply a given muscle make up the motor neuron pool for the
muscle.
• The building blocks for all movements are motor units, each comprising one motor neuron
together with all the skeletal muscle fibers that this neuron innervates.
Motor Control Hierarchy
The neural systems that control body movements can be conceptualized as being arranged in a
motor control hierarchy.
1) The highest level determines the general intention of an action. It includes areas involved
with memory and emotions, supplementary motor area, and association cortex.
2) The middle level establishes a motor program and specifies the postures and movements
needed to carry out the intended action, taking into account sensory information that
indicates the body’s position.
• Motor program is defined as the pattern of neural activity required to properly perform
the desired movement.
• This level includes sensorimotor cortex, cerebellum, parts of basal nuclei, some brainstem
nuclei.
3) The local level ultimately determines which motor neurons will be activated.
This area include levels of brainstem or spinal cord from which motor neurons exit.
 As the movement progresses, information about what the muscles are doing feeds back to
the motor control centers, which make program corrections.

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Voluntary Actions
Voluntary movement refer to actions that have the following characteristics:
1) The movement is accompanied by a conscious awareness, and
2) Attention is directed toward the action or its purpose.
Local Control of Motor Neurons
• The local control systems are the relay points for instructions to the motor neurons from
centers higher in the motor control hierarchy.
• The local control systems use information carried by afferent fibers from sensory receptors
in the muscles, tendons, joints, and skin of the body parts to be moved.
Interneurons
• The interneurons are important elements of the local level of the motor control hierarchy
because they integrate inputs from higher centers, peripheral receptors and other
interneurons.
• They are crucial in determining which muscles are activated and when.

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Local Afferent Input
The afferent fibers bring information from sensory receptors located in three places:
1) In the skeletal muscles controlled by the motor neurons,
2) In other nearby muscles, such as those with antagonistic actions, and
3) In the tendons, joints, and skin of body parts affected by the action of the muscle.
Function of Receptors
The receptors of afferent neurons monitor;
1) The length and tension of the muscles,
2) Movement of the joints, and
3) The effect of movements on the overlying skin.
Length-Monitoring Systems
• Stretch receptors embedded within muscles monitor muscle length and the rate of change
in muscle length.
• These receptors consist of peripheral endings of afferent nerve fibers wrapped around
modified muscle fibers are collectively called a muscle spindle.

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 • The modified muscle fibers within the spindle are known as intrafusal fibers.
• The skeletal muscle fibers that form the bulk of the muscle and generate its force and
movement are the extrafusal fibers.
Types of Muscle-spindle Stretch Receptors
• Nuclear chain fibers respond to the magnitude of stretch.
• Nuclear bag fibers responds to both the magnitude of the stretch and the speed of stretch
occurring.

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Mechanism of Activation
• An external force stretching the muscle also pulls on the intrafusal fibers, stretching them
and activating their receptor endings.
• The more or the faster the muscle is stretched, the greater the rate of receptor firing.

Contraction of the extrafusal fibers and the resultant shortening of the muscle remove tension on
the spindle and slow the rate of firing in the stretch receptor.

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 • Activation of stretch receptors initiates the stretch reflex.
• This reflex inhibits motor neurons of antagonistic muscles and activates neurons of the
stretched muscle.
• It also activates motor neurons of synergistic muscles, muscles whose contraction assists
the intended motion.

Alpha-Gamma Coactivation
• The motor neurons controlling the extrafusal muscle fibers are larger and are classified as
alpha motor neurons.
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 • The smaller motor neurons whose axons innervate the intrafusal fibers are known as
gamma motor neurons.
• Alpha and gamma motor neurons are generally coactivated.
Coactivation ensures that information about muscle length will be continuously available to
provide for adjustment during ongoing actions and to plan and program future movements.

Tension-Monitoring Systems
• The receptors to monitor muscle tension are the Golgi tendon organs.
• These are located in the tendons near their junction with the muscle.
• These are the endings of afferent nerve fibers wrap around collagen bundles in the tendon.
Mechanism of Activation
• When the muscle is stretched or the attached extrafusal muscle fibers contract, tension is
exerted on the tendon.
• This tension straightens the collagen bundles and distorts the receptor endings, activating
them.
• The tendon is stretched much more by an active contraction than stretching.

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The stretch receptors activate inhibitory synapses on motor neurons of the contracting muscle and
excitatory synapses on motor neurons of antagonistic muscles.

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The Withdrawal Reflex
• The withdrawal reflex excites the ipsilateral flexor muscles and inhibits the ipsilateral
extensor muscles.
• The crossed-extensor reflex excites the contralateral extensor muscles during excitation of
the ipsilateral flexor muscles.
• Ipsilateral means on the same side of the body.
• Contralateral means on the opposite side of the body from the stimulus.

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 The Brain Motor Centers
Cerebral Cortex
• The cerebral cortex is involved in the planning and ongoing control of voluntary
movements, functioning in both the highest and middle levels of the motor control
hierarchy.
• Sensorimotor cortex includes all parts of the cerebral cortex that act together to control
muscle movement.

Sensorimotor Cortex Parts

1) The primary motor cortex (the motor cortex).
2) The premotor area.
3) The supplementary motor cortex.
4) The somatosensory cortex.
5) Parts of the parietal-lobe association cortex.

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Subcortical and Brainstem Nuclei
• The basal nuclei form a link in a circuit that originates in and returns to sensorimotor cortex.
• These subcortical nuclei facilitate some motor behaviors and inhibit others.
Cerebellum
The cerebellum coordinates posture and movement and plays a role in motor learning.
Descending Pathways
The influence exerted by brain on posture and movement occurs via descending pathways to the
motor neurons.

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The pathways are of two types;
1) The corticospinal pathways originate in the cerebral cortex;
2) The brainstem pathways originate in the brainstem.

The Corticospinal Pathways

• The corticospinal pathways pass directly from the sensorimotor cortex to motor neurons in
the spinal cord.
• The corticospinal pathways are also called the pyramidal tracts or pyramidal system.
• Corticobulbar pathway begins in the sensorimotor cortex and ends in the brainstem.
• Neurons on one side of the brain control muscles on the other side of the body.

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 • Corticospinal pathways control predominately fine, precise movements.
Brain Stem Pathway
• Axons from neurons in the brainstem form pathways that descend into the spinal cord to
influence motor neurons.
• These pathways are referred to as the extrapyramidal system.
• The brainstem pathways are important in controlling muscles of the trunk for upright
posture, balance, and walking.
Muscle Tone
• There is a slight and uniform resistance when muscle is stretched by an external force. This
resistance is known as muscle tone.
• Muscle tone is due both to the passive elastic properties of the muscles and joints and to
the degree of ongoing alpha motor neuron activity.
Abnormal Muscle Tone
• Abnormally high muscle tone is called hypertonia.
• The increased resistance is due to a greater-than-normal level of alpha motor neuron
activity.
• Hypertonia usually occurs with disorders of the descending pathways that normally inhibit
the motor neurons.
Forms of Hypertonia
• Spasticity is a form of hypertonia in which the muscles do not develop increased tone until
they are stretched a bit.
• Rigidity is a form of hypertonia in which the increased muscle contraction is continual and
the resistance to passive stretch is constant.
• Spasms are brief contractions of muscles.
• Cramps are prolonged and painful muscle contractions.
Hypotonia
• Hypotonia is a condition of abnormally low muscle tone, accompanied by weakness,
atrophy, and decreased or absent reflex responses.
• The term flaccid is often used to describe hypotonic muscles.
Maintenance of Upright Posture and Balance
• To maintain balance, the body’s center of gravity must be maintained over the body’s base.

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 • Postural reflexes are utilized to maintain upright posture balance by adjustment of center
of gravity.
Components of Postural Reflex
• The afferent pathways of the postural reflexes come from the eyes, the vestibular apparatus,
and the receptors involved in proprioception (joint, muscle).
• The efferent pathways are the alpha motor neurons to the skeletal muscles.
• The integrating centers are neuron networks in the brainstem and spinal cord.
Walking
• Walking is initiated by allowing the body to fall forward to an unstable position and then
moving one leg forward to provide support.
• When the extensor muscles are activated on the supported side of the body to bear the
body’s weight, the contralateral extensors are inhibited to allow the non-supporting limb
to flex and swing forward.
• The activity of interneuron networks in the spinal cord brings about the cyclical, alternating
movements of locomotion.
• These pattern generators are controlled by corticospinal and brainstem descending
pathways and affected by feedback and motor programs.

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 Consciousness, the Brain, and Behavior
States of Consciousness
It refers to whether a person is awake, asleep, drowsy.
State of consciousness is defined in two ways:
1) By behavior ranging from maximum attentiveness to coma, and
2) By the pattern of brain activity that can be recorded electrically.
Electroencephalogram
• The pattern of brain activity that can be recorded electrically. This record, known as the
electroencephalogram (EEG).
• This describes the electrical potential difference between different points on the surface of
the scalp.
Characteristics
• Electrical currents in the cerebral cortex due predominantly to summed postsynaptic
potentials are recorded as the EEG.
• The wave’s amplitude, measured in microvolts (µV) indicates how much electrical activity
of a similar type is going on.
• The wave’s frequency indicates how often the wave cycles from its maximal amplitude to
its minimal amplitude and back. The frequency is measured in hertz.
• Rhythm generators in the thalamus are probably responsible for the wavelike nature of the
EEG.

The Waking State

• The EEG wave pattern of an awake, relaxed adult whose eyes are closed is a slow
oscillation of 8 to 13 Hz known as the alpha rhythm.

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 • The alpha rhythm is recorded best over the parietal and occipital lobes and is associated
with decreased levels of attention.
• The alpha rhythm is replaced by lower-amplitude, high-frequency (>13 Hz) oscillations,
the beta rhythm during attentive conditions.
• This transformation, known as the EEG arousal, is associated with the act of paying
attention to a stimulus.

Sleep
• When sleep occurs, the EEG shifts toward slower-frequency, higher-amplitude wave
patterns known as the theta rhythm (4–8 Hz) and the delta rhythm (slower than 4 Hz).
• There are two phases of sleep whose names depend on whether or not the eyes move behind
the closed eyelids.
Nonrapid Eye Movement (NREM)
• The EEG waves during NREM sleep are of high amplitude and slow frequency, so it is
also referred to as slow-wave sleep.
• NREM is divided into four stages.
• Each successive stage is characterized by an EEG pattern with a slower frequency and
higher amplitude than the preceding one.
• Sleep begins with the progression from stage 1 to stage 4, which normally takes 30 to 45
min.
• The process then reverses itself; the EEG ultimately resuming the low-voltage, high-
frequency, asynchronous pattern characteristic of the alert, awake state.
Rapid Eye Movement (REM)
• REM sleep is also called paradoxical sleep because the sleeper is difficult to arouse despite
having an EEG characteristic of the alert, awake state.

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 • In fact, brain O2 consumption is higher during REM sleep than during the NREM or awake
states.

Neural Mechanisms of States of Consciousness

Neurons of certain brainstem nuclei give rise to axons that diverge to affect wide areas of the brain
is known as the reticular formation [reticular activating system (RAS)].
• Components of the RAS that release norepinephrine, serotonin, or acetylcholine are
involved in controlling the various states of consciousness.
• During waking, the aminergic neurons (those that release norepinephrine or serotonin)
dominate, and during REM sleep the cholinergic neurons are dominant.

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 • There are two additional areas in the forebrain that are involved in the control of sleep-
wake cycles.
• The preoptic area of the hypothalamus promotes slow-wave sleep by inhibitory
GABAergic inputs to the thalamocortical neurons and to the midbrain reticular formation.
• It also inhibits activity within the posterior hypothalamus that stimulates wakefulness.

Conscious Experiences
Conscious experiences are those things we are aware of either;
1) Internal, such as an idea, or
2) External, such as an object or event.
Selective Attention
• The term selective attention means avoiding the distraction of irrelevant stimuli while
seeking out and focusing on stimuli that are momentarily important.
• The person stops what he or she is doing and looks around, listening intently and turning
to face toward the stimulus source, a behavior called the orienting response.
The Pre-attentive Processing
• The nervous system evaluate the importance of incoming sensory information called the
preattentive processing.
• It directs our attention toward the part of the sensory world that is of particular interest and
prepares the brain’s perceptual processes for it.

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Habituation
• If a stimulus is repeated but is found irrelevant, the behavioral response to the stimulus
progressively decreases, a process known as habituation.
• Habituation involves a depression of synaptic transmission in the involved pathway, by
prolonged inactivation of calcium channels in presynaptic axon terminals.
Neural Mechanisms for Selective Attention
• The locus ceruleus connected to the parietal cortex and to many other parts of the central
nervous system.
• It helps determine which brain area is to gain temporary predominance in the ongoing
conscious experience.
• Norepinephrine acts as a neuromodulator to enhance the signals transmission by certain
sensory inputs.

Motivation and Emotion

Motivation
• Motivation is the ability to direct behavior toward specific goals.
• Primary motivated behavior is behavior related directly to homeostasis.
• Repetition of a behavior indicates it is rewarding, and avoidance of a behavior indicates it
is punishing.
The Mesolimbic Dopamine Pathway
• The component involved in motivation is known as the mesolimbic dopamine pathway.
• Meso-because it arises in the midbrain (mesencephalon) area of the brainstem;
• Limbic because it goes to areas of the limbic system; and
• Dopamine because its fibers release the neurotransmitter dopamine.

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Emotion
Emotional behavior includes such complex behaviors as the passionate defense and such simple
actions as laughing, sweating, crying, or blushing.
Physiological Aspects
1) The anatomical sites where the emotional value of a stimulus is determined;
2) The hormonal, autonomic, and outward expressions and displays of response to the
stimulus (emotional behavior); and
3) The conscious experience (inner emotions) such as feelings of fear, love, anger, joy,
anxiety, hope etc.
Neural Component
• Limbic areas of the brain handle inner emotions but there is no single “emotional system.”
• The amygdala and the region of association cortex on the lower surface of the frontal lobe
are involved in most emotional states.

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The amygdala interacts with other parts of the brain that can influence emotions about external
stimuli, decision making, memory, attention, homeostatic processes, and behavioral responses.

Altered States of Consciousness

Schizophrenia
• It is a disease in which information is not properly regulated in the brain.
• The symptoms of schizophrenia include hallucinations (false sensations), and delusions
(false belief).
• Schizophrenics become withdrawn, are emotionally unresponsive, and experience
inappropriate moods.
The Mood Disorders
• The term mood refers to a sustained inner emotion that affects a person’s perception of the
world.
• When the sense of control over mood is lost the mood disorders occurs.
Depressive Disorders (Depression)
• This condition is characterized by a persistent sadness, loss of energy, interest, or pleasure;
anxiety; irritability; disturbed sleep; and thoughts of death or suicide.

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 • It is associated with decreased neuronal activity and metabolism in the anterior part of the
limbic system and nearby prefrontal cortex.
Bipolar Disorders
• The term bipolar disorders describes swings between mania and depression.
• Mania is characterized by an abnormally and persistently excited mood, sometimes with
euphoria (exaggerated sense of well-being), racing thoughts, excessive energy,
overconfidence, and irritability.

Learning and Memory

Learning
• Learning is the acquisition and storage of information as a consequence of experience.
• It is measured by an increase in the possibility of a particular behavioral response to a
stimulus.
Memory
• Memory is the relatively permanent storage form of learned information.
• The term memory encoding defines the neural processes that change an experience into
the memory of that experience.

Categories of Memory
1) Declarative memories are involved in remembering facts and events.
2) Procedural memories are memories of how to do things.
a) Working memory (short-term memory) retains incoming information for a short time.
b) Long-term memories may be stored for days to years and recalled at a later time.
The process by which short-term memories become long-term memories is called consolidation.
The Neural Basis of Learning and Memory
• Working memory requires ongoing graded or action potentials.
• Formation of long-term memory probably involves changes in second-messenger systems
and protein synthesis.

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Amnesia
• Amnesia is defined as the loss of memory.
• Anterograde amnesia results from damage to the limbic system and associated structures.
Consolidation is impaired.
• Retrograde amnesia is characterized by loss of memories for all that happened for a
variable period of time.

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