By: Rediet Belay (B.

Pharm: MSc)

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  CNS - Basics

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 Organs & Divisions of the Nervous System
 Central nervous system (CNS) — Brain & Spinal Cord
 Peripheral nervous system (PNS) —All Nerves

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  PNS - Autonomic division

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 Cells of the Nervous System :
 Two types of cells: Neurons (nerve cell) & Glia (Neuroglia)
1. Neurons :
 The basic cellular building-block of the NS

 is an electrically excitable cell that processes & transmits

information through electrical & chemical signals

 Consist of three parts:

⟾ Cell body - main part

⟾ Dendrites - branching projections that conduct impulses
to cell body of neuron
⟾ Axon – an elongated projection that conducts impulses
7 away from cell body of neuron
  Myelin sheath – is an Electrical Insulator important for
facilitating impulse Conduction
 Node of Ranvier – Short segment of the Axon not covered by
8 Myelin sheath
 Cells of the Nervous System(Cont….)

 Neurons are classified according to function :

i. Sensory neurons: conduct impulses to the spinal cord &

brain; AKA - Afferent Neurons

ii.Motor neurons: conduct impulses away from brain & spinal

cord to muscles & glands; AKA - Efferent Neurons

iii.Interneurons: conduct impulses from sensory neurons to

motor neurons; AKA - Central or Connecting Neurons

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 Cells of the Nervous System(cont…..)
2. Glia (Neuroglia) :
 Glia cells (Greek for Glue)⟾ hold the functioning neurons together,
protect them & regulate neuron function
↪ i.e. Support neurons, hold the cells of nervous tissue together
structurally & functionally

 3 main types of connective tissue cells (Glia Cells) of the CNS :

i. Astrocytes - Star-shaped cells that Anchor small blood vessels

to neurons

ii. Microglia - Small cells that Move in inflamed brain tissue

carrying on Phagocytosis

iii.Ependymal cells (line the Ventricles & make CSF) &

Oligodendrocytes (make Myelin Sheaths on Axons in the CNS )
10 N.B. (Schwann cells make myelin sheaths on Axones in PNS only)
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 Reflex Arcs :
 Nerve impulses are conducted from Receptors to Effectors
over neuron pathways or Reflex Arcs;
↪ conduction by a reflex arc results in a Reflex
(i.e. Contraction by a muscle or Secretion by a gland)

 2-Neuron Arcs (the simplest reflex arcs):

↪ consisting of sensory neurons synapsing in the SC with

motor neurons

 3-Neuron Arcs :

↪ consist of sensory neurons synapsing in the SC with

interneurons that synapse with motor neurons
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Patellar reflex.
13 The neural pathway involved in the patellar (“knee-jerk”) reflex.
 Nerve Impulses(AP) :
 Deff ↣ self-propagating wave of electrical disturbance that
travels along the surface of a neuron membrane; AKA - Action
Potentials (AP)

 Where does impulse conduction originate?

↪ Starts in Receptors, the beginnings of dendrites of

sensory neurons
↪ The end of the sensory neuron’s Axon  interneuron 
conduction through the motor neuron  Response

 What are some types of stimuli that initiate nerve impulses?

↪ Pressure, Temperature, Chemical changes

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 Nerve Impulses (CONT…..)
 Mechanism :

 At rest, the neuron’s membrane is slightly +ve on the outside

⟾ Polarized - from a slight excess of Na+ on the outside

 A stimulus triggers  Opening of Na+ channels  Inward

movement of Na+  Depolarizes the membrane by making
the inside more +ve than the outside at the stimulated point
↪ this Depolarization is a Nerve Impulse (AP)

 The stimulated section of membrane immediately Repolarizes,

but by that time the depolarization has already triggered the
next section of membrane to depolarize:

↪ thus propagating a wave of electrical disturbances

(depolarizations) all the way down the membrane
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 Phases of an Action Potential :

 Phase 1: Depolarization - Sodium (Na+) Influx

 Phase 2: Repolarization - Potassium (K+) Efflux

 Phase 3: Hyperpolarization - (Undershoot): Leakage of

excess K+ ions through the Slow closing K+channels

 Phase 4 : Return to the RMP from Hyperpolarization:

Na+/K+ -Pump

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 The Synapse :
 Deff –n - the place where impulses are transmitted from one
neuron to another (postsynaptic neuron) or to an effector cell

 NTs bind to specific receptor molecules in the membrane of a

postsynaptic neuron ↣ Opening ion channels ↣ stimulating
impulse conduction by the membrane

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 Synaptic Transmission:
i. AP arrives at axon terminal of the presynaptic neuron &
opens voltage-gated Ca2+ channels

ii. Synaptotagmin protein binds Ca2+ & promotes fusion of

synaptic vesicles with axon membrane

iii. Exocytosis (release) of NT occurs

iv. NT diffuses & binds to receptors (often chemically/Ligand

gated ion channels) on the postsynaptic neuron

v. Ion channels are opened, causing an excitatory or

inhibitory event (EPSP or IPSP)
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 Chemical synapses
transmit signals from
one neuron to another
Presynaptic
using NT. neuron

Postsynaptic Presynaptic
neuron neuron

Action potential
arrives at axon terminal.
1

2 Voltage-gated Ca2+
channels open and Ca2+
Mitochondrion
enters the axon terminal.
Ca2+ Ca2+ Ca2+
Axon Ca2+
3 Ca2+ entry causes terminal Synaptic
neurotransmitter- cleft
containing synaptic Synaptic
vesicles to release their vesicles
contents by exocytosis.
4 Postsynaptic
neuron

Neurotransmitter
diffuses across the synaptic
ReuptakeEnzymatic
cleft and binds to specific degradation
receptors on the
Ion movement
postsynaptic membrane. Diffusion away
Graded potential from synapse

5 Binding of neurotransmitter
opens ion channels, resulting in
graded potentials.
6 Neurotransmitter effects are
terminated by reuptake through
transport proteins, enzymatic
degradation, or diffusion away
from the synapse.

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Figure 11.17
 Termination of Neurotransmitter Effects :
 Within a few milliseconds, the NT effect is terminated by :
⟾ Degradation by enzymes: MAO & COMT
⟾ Reuptake by axon terminal
⟾ Diffusion away from the synaptic cleft

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 Types of postsynaptic potentials
i. EPSP — Excitatory postsynaptic potentials
ii. IPSP — Inhibitory postsynaptic potentials

i. Excitatory Synapses & EPSPs :

 NT binds to & opens chemically gated channels that allow
simultaneous flow of Na+ & K+ in opposite directions

 Na+ influx ˃ ˃˃ K+ efflux, causing a net depolarization

 EPSP trigger AP

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 Membrane potential (mV)

An EPSP is a local
depolarization of the
postsynaptic membrane
that brings the neuron
closer to AP threshold.
Neurotransmitter binding
opens chemically gated
Threshold ion channels, allowing
the simultaneous pas-
sage of Na+ and K+.

Stimulus

Time (ms)
(a) Excitatory postsynaptic potential (EPSP)

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Figure 11.18a
ii. Inhibitory Synapses & IPSPs :

 NT binds to & opens channels for K+ or Cl–

 Causes a hyperpolarization (the inner surface of

membrane becomes more negative)

 Reduces the postsynaptic neuron’s ability to produce

an action potential

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 Membrane potential (mV)

An IPSP is a local
hyperpolarization of the
postsynaptic membrane
and drives the neuron
away from AP threshold.
Neurotransmitter binding
opens K+ or Cl– channels.
Threshold

Stimulus

Time (ms)
(b) Inhibitory postsynaptic potential (IPSP)

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Figure 11.18b
 Neurotransmitters (NTs)
 50 or more NTs have been identified

 Classified by chemical structure & by function

 Chemical Classes of Neurotransmitters :

i. Acetylcholine (Ach)
 Released at neuromuscular junctions & some ANS neurons
 Synthesized by enzyme Cholineacetyltransferase

 Degraded by the enzyme Acetylcholinesterase (AChE)

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 Chemical Classes of NTs(cont….)
ii. Biogenic amines include:
 Catecholamines

 Dopamine (DA),
 Norepinephrine (NE) &
 Epinephrine (E)

 Indolamines

 Serotonin (5-HT) & Histamine

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 Chemical Classes of NTs
iii. Amino acids include:
 GABA - Gamma ()-aminobutyric acid
 Glycine
 Aspartate
 Glutamate
iv. Peptides (neuropeptides )include:
 Substance P
↪ Mediator of pain signals
 Endorphins
↪ Act as natural opiates; reduce pain perception
 Gut-brain peptides

32 ↪ Somatostatin & cholecystokinin

 Chemical Classes of NTs Cont..

v. Purines such as ATP:

 Act in both the CNS & PNS
 Provoke pain sensation
vi. Gases & lipids :
 Nitric oxide (NO)

 Carbon monoxide (CO)

 Endocannabinoids :

 synthesized on demand from membrane lipids

 Involved in learning & memory
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 Functional Classification of NTs :

 NT effects may be excitatory (depolarizing) or inhibitory

(hyperpolarizing)

• GABA & Glycine are usually inhibitory

• Glutamate & Aspartate are usually excitatory

• Acetylcholine:
↪ Excitatory at neuromuscular junctions in skeletal muscle

↪ Inhibitory in cardiac muscle

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  SITES OF DRUG ACTION
 Most CNS drugs produce their effects by modifying some
steps in chemical synaptic transmission:
↪ either presynapticaly or postsynapticaly

i. Presynapticaly – by altering the synthesis, storage,

metabolism, & release of NTs
 E.g. Reserpine - interferes with intracellular storage of
monoamine NTs ⟾ depresses synaptic transmission

 Blockade of NT catabolism inside the nerve terminal ⟾

↑se concentrations & amount of NT released per impulse.

 The stimulant Amphetamine - induces the release of

catecholamines from adrenergic synapses
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  Tetanus toxin - blocks the release of NTs.
 Cocaine - blocks the uptake of catecholamines at adrenergic
synapses & thus potentiates the action of these amines.
 Anticholinesterases - block the degradation of Ach & thereby
prolong its action.

ii. Postsynapticaly - on the NT receptor :

 drugs can act either as NT agonists :
↪ e.g. Opioids, which mimic the action of enkephalin, or

 they can block receptor function (act as NT antagonist) :

↪ e.g. Strychnine’s - blockade of the receptor for inhibitory
NT Glycine → blockade of inhibitory processes results in
36 excitation → Strychnine’s convulsant action.
 Fig. Sites of drug action.
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 TNX
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