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.
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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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