Neuron

- basic functional unit of CNS

- main parts: a. Soma (neuronal body) – main body, acts as a processing center for the nerve fiber

b. Protoplasmic processes

1) axon extents from the soma into the peripheral nerves that leaves the spinal cord
- larger projection that transmits AP away from the soma. It
originates a bulge in the soma (axon hillock) and ends in a nerve
terminal which contains vesicles filled with neurotransmitters and
can be released when AP is propagated down the axon. Hence it
ultimately provides an electrochemical connection to other
neurons

2) dendrites branching projections of the soma

- conducts impulse towards the soma
- conducts repulses away from the soma
- plasma membrane is densely populated with ligand-gated receptor to
provide high affinity binding sites for chemical transmitters
released by surrounding neurons.

Synapse – joint junction from one neuron to the next

- determine the directions that the neurons signal will spread in the nervous system
- site for control of signal transmission
- selective in action (block weak signals while allowing strong signal to pass)
- amplify weak signal and channel the signal in many direction
- excitatory and inhibitory signal
- conduction of synapse: transmit signals in one direction (from presynaptic neuron to postsynaptic
neuron)

Types of Synapse
1. chemical synapse
2. electrical synapse

Chemical Synapse
- signal transmission in CNS
- 1st neuron secretes neurotransmitter and acts on receptor protein in the membrane of the next neuron to
excite the neuron
- acetylcholine, Norepinephrine, histamine gamma amino butyric acid (GABA), glycine, serotonin, and
glutamate

Electrical Synapse
- characterized by direct open fluid channels that conduct electricity from one cell to the next
- has small protein tubular structure (gap junctions) that allow free movement of ions from interior of
one cell to the interior of the next cell

Structure of Synapse
1. Presynaptic terminal
- end of nerve fibril
- secretes either: excitatory neurotransmitter (excite the postsynaptic neuron)
inhibitory neurotransmitter ( inhibit the postsynaptic neuron)
- Shaped: small round or oval knobs (terminal knob), button, end-feet or synaptic knob)
- Basic structures:
a) transmitter vesicles –contains the transmitter substance
b) mitochondria – provide ATP, which supplies energy to synthesize new transmitter substance

2. Postsynaptic neuronal membrane

- 1. Receptor proteins
- either: excitatory receptor or inhibitory receptor
- has two components
a) binding component – protrudes outward from the entrance into the synaptic cleft
- binds with neurotransmitter from the presynaptic terminal

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 b) Ionophore component – passes all the way through the membrane to the interior of the
postsynaptic neuron
- has two types:
I) ion Channels
a) Cation channels – allow Na ions to pass (sometimes K and/or
Ca ions)
- lined with negative charges
- opens by excitatory transmitter

b) Anion channels – allow mainly Cl ions to pass

- open by inhibitory transmitter

***opening and closing of ion channels provide a means for rapid control of
post-synaptic neuron

2) Second messenger Activator

- not an ion channels but instead is a molecule that protrudes into the cell
cytoplasm and activates one or more substances inside the
postsynaptic neuron
-achieved prolonged neuronal action (ion channels are not suitable for
prolonged postsynaptic neuronal change because channels close
within milliseconds)
- G proteins

3. Synaptic cleft – space separating the pre-synaptic neuron from neuronal soma

How is an AP propagated along a nerve axon?

An AP initiated at one site in the nerve plasma membrane is propagated throughout the rest of the nerve by
self-perpetuating process which involves the local flow of current (positive charge) from depolarized sites on the
inside surface of the cell membrane to adjacent, normally polarized membrane sites available for activation.

Hence the original AP does not propagate along the nerve fiber but rather results in the sequential
generation of identical AP, which propagates unidirectionally away from the site of the original AP.

Excitation:
1. Opening of Na channels
- influx of + charges to the interior of the postsynaptic cell
- raise the MP in the positive direction
2. depressed conduction through Cl or k channels or both
3. varies changes in the internal metabolism of the cell to excite cell activity
- increase in number of excitatory membrane receptor
- decrease in number of inhibitory membrane receptor

Presynaptic inhibition
- inhibition often occurring at the presynaptic terminal before the signal reaches the synapse
- due to discharge of inhibitory transmitter
- e.g. GABA

*** Generation of AP : initial segment of the axon leaving the neuron

reason: soma has relatively few voltage-gated sodium channels in its membrane, which makes it difficult
for EPSP to open the required number of Na channel to elicit AP

initial segment of the axon has numerous voltage-gated Na channels

Spread of AP
Travels peripherally along the axon and usually backward over the soma, sometimes backward to the
dendrites (but could not cause excitable due to less voltage-gated Na channels same with soma)
`

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Two factors which are the main Determinants of the Velocity of AP Propagation
1. Myelination increases the speed of AP propagation along the axon. The Node of Ranvier provide a
sequence of high efficiency sites to transmits the nerve impulse as it jumps between nodes

2. Diameter of t\he nerve fibers also positively influences the velocity of AP propagation. Hence large
myelinated nerve fibers such as those innervating skeletal muscle, show the highest conduction velocity.
Small, unmyelinated nerve fibers, such as the sympathetic postganglionic fibers, show a low speed of
impulse propagation

How are Chemical messages transmitted between nerve cells?

Nerve synapses represent the communicating structure between the axon terminals of one nerve
(presynaptic neuron) and the dendrites or cell body of a second, target nerve (postsynaptic neuron).

The space between the two adjacent nerves that must be spanned to permit the communication of the nerve
signal is called the Synaptic Cleft.

When a nerve impulse is propagated to the axon terminal of the transmitting nerve, the influx of Ca ions
through voltage gated-gated channels in the plasma membrane of the presynaptic nerve terminal triggers the release
of chemical neurotransmitters from vesicles stored in the axon terminal.

Neurotransmitters diffuse across the synaptic cleft and bind to specific high affinity receptors on the plasma
membrane of the postsynaptic neuron. If the signal is adequate, the activation these ligand-operated receptors
initiates intracellular signals that alter the electrical and functional properties of the postsynaptic neuron .

Mechanism by which action potentials causes transmitter release from the pre-synaptic terminal
 pre-synaptic membrane contains large number of voltage gated calcium channels
 AP depolarizes the terminal, channels open and allow entry of calcium ions to flow into the terminal
 Ca bind with release site on the inside of the pre-synaptic membrane which cause the transmitter
vesicle in the terminal fuse with the release site and to open through the membrane to the exterior
(exocytosis)

Factors that determine the concentration of neurotransmitter in the synaptic cleft

1. Amount of neurotransmitter released by the presynaptic cleft

2. Passive diffusion of the transmitter down its concentration gradients from the synaptic cleft to adjacent
areas of extracellular fluid

3. Active uptake of neurotransmitter by transport protein in the plasma membrane of the surrounding neurons

4. Breakdown of neurotransmitter molecules by enzymes located in the presynaptic cleft or I the plasma
membrane of the presynaptic or postsynaptic neurons .

What is Saltatory Conduction?

Saltatory Conduction refers to the unidirectional jumping of depolarization from one node of Ranvier to the
neighboring node, which provides a rapid regeneration of nerve impulses for long distances.

The axons of some nerves are populated by cells called oligodentrocytes (Brain and spinal cord) or
Schwann’s cells (peripheral nerves).

The plasma membrane of oligodentrocytes and Schwann’s cells contains a high density of a lipid called
Myelin, and the thick layering of the plasma membranes of these cells at periodic sites along the nerve axon forms
myelin blocks, which insulate the underlying nerve cell membrane from excitatory stimuli.

Between their myelin locks are the node of Ranvier, which are myelin- free sites where the cell membrane
remains exposed to the ECF and densely populated with voltage-gated Na channels to promote AP.

Fatigue of the synapse

- due to exhaustion of the store of transmitter substance in the presynaptic terminal

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Effects of the following on synaptic transmission:
1. acidosis – increase neuronal excitability
2. alkalosis – decrease neuronal excitability
3. hypoxia – inexcitability
4. Theobromine, caffeine, theophylline – increase neuronal excitation
5. strychnine – increase neuronal activity
6. most anesthetic – decrease neuronal activity

How do the chemical neurotransmitters from different from different presynaptic neurons interact to
regulate the level of excitability of the postsynaptic neurons?

Presynaptic neurons can release neurotransmitters that either promote or inhibit excitation of the
postsynaptic neurons.

Neurotransmitters released from excitatory presynaptic neurons produce a small. A local, nonpropagated
depolarization of the post synaptic neuron, which is called an EXCITATORY POSTSYNAPTIC POTENTIAL
(EPSP).

Because the amplitude of this depolarization is rarely sufficient to bring the membrane potential to the
threshold required for the initiation of an AP, the additive effect of multiple EPSP is generally required to initiate an
AP at the postsynaptic membrane.

Conversely, neurotransmitters released from inhibitory presynaptic neurons induce a small, local,
nonpropagated hyperpolarization when they bind to their receptors on the plasma membrane of the postsynaptic
neuron.

The local hyperpolarization is called an INHIBITORY POSTSYNAPTIC POTENTIAL (IPSP).

The algebraic summation of these grade changes in potential determines whether the membrane potential of
the postsynaptic nerve cell depolarizes sufficiently to reach its firing threshold and initiate an AP.

Differences between temporal and Spatial summation

Temporal summation refers to the additive effect of sequential multiple EPSPs or IPSPs originating from a single
presynaptic neuron on the membrane potential of the postsynaptic neuron.

For example: the repetitive firing of a single excitatory presynaptic neuron may result in summated
EPSP, which may depolarize the membrane potential to its firing threshold for AP generation.
Because an EPSP results I only a small increment of membrane depolarization that is not sufficient
to inactivate voltage-gated Na channels, a refractory period does not occur. This permits multiple
EPSPs to exert a summating depolarizing effect on the MP of the post synaptic neuron.

Spatial Summation refers to the additive effect of multiple EPSPs or IPSPs simultaneously
originating from different presynaptic neurons on the MP of the postsynaptic neuron (i.e., the
neurotransmitter signals have different geographic origin) Under physiologic conditions, spatial
and temporal summation act concurrently to regulate the membrane potential of the post synaptic
neuron.