CENTRAL NERVOUS SYSTEM:
An Introduction(Guyton & Hall, 13th Edition, Chapter 46)
Dr. Ayisha Qureshi
Professor
MBBS, MPhil
Learning Objectives
• By the end of the lecture, you should be able to:
1. Name the parts of the Nervous System.
2. Name the various parts of a neuron.
3. Explain the physiological basis of Resting Membrane Potential.
4. Name the various phases of an Action Potential and describe their ionic basis.
5. Differentiate between Action and Graded Potential.
6. Explain the mechanism of transmission across a chemical synapse.
7. Enlist and describe the properties of a synapse.
8. Differentiate between neurotransmitters and neuromodulators.
The Brain is the most complex tissue of the body!! It mediates behavior from
simple movements & sensory perceptions to thinking, learning and memory.
Brain’s main function, thinking, is hardly
understood at all.
THE NERVOUS SYSTEM CAN BE DIVIDED INTO
CENTRAL, PERIPHERAL AND AUTONOMIC
NERVOUS SYSTEM.
Nervous System
CENTRAL NERVOUS SYSTEM
Brain Spinal Cord
PERIPHERAL NERVOUS SYSTEM
Sensory Input Motor Output
Autonomic nervous system
What makes up the brain, the spinal
cord and the peripheral nerves?
What makes up the brain, the spinal
cord and the peripheral nerves?
NEURONS.(In most places, neurons are supported by neuroglia.)
NERVE CELLS HAVE FOUR SPECIALIZED REGIONS:
1. Cell body
2. Dendrites
3. Axon, and
4. Presynaptic terminals
RECALL THE FOLLOWING:
• Structure of a Neuron
• Resting Membrane Potential
• Action Potential
• Synapse
Structure of A Neuron!
The structure of the neuron also determines the
function of the neuron by determining the direction of
flow of information…
This information transmission takes place thru action potentials or
simply “Nerve Impulses”, thru a succession of neurons, one after
another.
These nerve impulses may be:
1.Blocked,
2.Changes from a single impulses into repetitive impulses, OR
3.Integrated with impulses from other neurons.
Thru synapses!
How are neurons connected?
SYNAPSE
A synapse is a an area of functional contact & anatomical differentiation between 2 neurons.
• Action potentials cannot travel across the synapse.
• Nerve impulse is carried by neurotransmitters (NT)which transmit the nerve impulse from one nerve cell to the next across the synapse.
• The structure of synapse consists of: – presynaptic terminal (NT are synthesized & released)
– post synaptic terminal (has neuroreceptors in the membrane)
– synaptic cleft
How many synapses
are in one neuron? 1,000 to 10,000!!
CLASSIFICATION OF
SYNAPSES:
Classification
Chemical synapse
Electrical synapse
Mixed synapse
Physiological/functional
Types of Synapses:
1. Chemical Synapse (transmission thru chemicals i.e. NT)
throughout the CNS
2. Electrical Synapse (Gap Junctions)
B/w the cardiac muscles and b/w visceral smooth muscle
- Impulse conducted without release of NT
- Synaptic gap only 2-3 nm
- No synaptic delay
- Unidirectional & Bidirectional conduction
3. Mixed Synapse i.e. having both electrical & chemical regions
Chemical synapses have one important characteristic that
makes them highly desirable for transmitting most nervous
system signals: Transmission of signals in one direction
(from the presynaptic neuron to the postsynaptic neuron).
This is the principle of one-way conduction at chemical
synapses. Electrical synapses often transmit signals in
either direction.
ROLE OF CALCIUM IONS
Ca ions enter the presynaptic terminal
↓
Bind with the RELEASE SITES (special molecules present on the inside of the presynaptic membrane)
↓
Release sites open up through the presynaptic membrane
↓
Transmitter vesicles release their NT through these release sites
↓
With each action potential a few vesicles will empty their NT content into the cleft.
(about 2000-10,000 molecules of NT are present in each vesicle)
Mechanism of Synaptic Transmission:• Action potential reaches the presynaptic terminal
↓
• Voltage-gated Ca2+ channels open
↓
• Influx of Ca2+
↓
• Synaptic vesicles fuse with membrane (exocytosis)
↓
• Neurotransmitter (NT) is released into the synaptic cleft and diffuse to the postsynaptic terminal
↓
• NT binds to neuroreceptor on postsynaptic membrane
↓
• Causes either the ion channels to open OR the second messenger system to be activated.
↓
• If threshold is reached then action potential is initiated
↓
• The NT is degraded by the specific enzymes in the synaptic cleft.
Fate of Neurotransmitters:
Fate of the Neurotransmitter:
The NT dissociates from the Receptor & can have either of
the 3 fates:
• Enzymatic Degradation: A portion of it is inactivated by
the enzymes present in high concentration at the
postsynaptic membrane.
• Re-uptake of remaining NT by Pre-synaptic neuron and
Re-used.
• Diffusion into the blood stream.
The excitation or inhibition of the post synaptic neuron will
depend upon the neuronal receptor characteristic.
The NT acts on the Receptor proteins present
on the Post-synaptic membrane
The Post-synaptic membrane contains large number of RECEPTOR
PROTEINS, which have 2 parts:
1. A binding component (protruding outwards into the synaptic cleft)
2. An ionophore component (passing all the way through the
membrane) which can be of 2 types:
a. An Ion Channel: that allows passage of specific ions.
OR
a. A Second messenger activator: that activates one or more
substances inside the postsynaptic neuron.
Why the need for second messenger system when
you already have a very rapid ion channel system
present?
Many functions of the nervous system, e.g learning & memory, require
prolonged changes in neurons for days to months after the initial transmitter
substance is gone.
The ion channels are not suitable for causing prolonged postsynaptic
neuronal changes because these channels close within milliseconds after
the transmitter substance is no longer present.
Prolonged postsynaptic change is achieved by activating a “second
messenger” chemical system inside the postsynaptic neuronal cell itself.
Why the need for second messenger system when
you have already have a very rapid ion channel
system present?
Receptor Proteins/ Postsynaptic Receptors
Binding Component
Ionophorecomponent
Ligand gated Ion channel
Cation Channels: Excitatory
Anion Channels: Inhibitory
Second Messenger Activator
Why have excitatory or inhibitory receptors
when we already have ion channel or
second messenger system for activation?
Why have excitatory or inhibitory receptors
when we already have ion channel or
second messenger system for activation?
This gives an additional dimension to nervous
function, allowing restraint/control of nervous
action and excitation.
ELECTRICAL EVENTS DURING
NEURONAL EXCITATION
(as studied in the anterior motor neurons)
Recall resting membrane potential please!
MEMBRANE POTENTIAL CHANGES
IN THE POSTSYNAPTIC NEURON
•The question we must answer is:
“How do different postsynaptic receptors lead to
excitation or inhibition of the neuron?”
How do different postsynaptic receptors lead to excitation or
inhibition of the neuron?
(By generation of Graded Potential thru excitation or inhibition.)
EXCITATION
(making the potential less
negative)
• Opening of Na
channels…
• Decreased conduction
thru chloride or potassium
channels or both,
• Increase in the no. of
excitatory membrane
receptors or decrease in
the no. of inhibitory
membrane receptors
INHIBITION
(making the potential more
negative)
• Opening of chloride ion channels…
• Increase in conductance of potassium ions out of the neuron
• Activation of receptor enzymes that inhibit metabolic functions that increase the number of inhibitory membrane receptors or decrease the number of excitatory receptors.
Types of Graded Potential
• Na Influx causes an increased
positivity in the neurons.
• This excitation that leads to
depolarization and is called an
Excitatory Postsynaptic
Potential (EPSP).
IPSP
(Inhibitory Postsynaptic Potential)
• Cl influx or K efflux of causes increased negativity inside the neuron leading to hyperpolarization which is called Inhibitory Postsynaptic Potential (IPSP).
EPSP
(Excitatory Postsynaptic Potential)
The 3 states of a neuron & effect of ion movement.
Depending upon the type of Graded Potential that is generated
(EPSP or IPSP) by their activation, the Receptor Proteins are
labelled as EXCITATORY OR INHIBITORY in nature.
A Word of Warning!
Discharge of a single presynaptic terminal can never
increase the neuronal potential from −65 millivolts all the
way up to −45 millivolts.
About 40 to 80 synapses must discharge for a single
anterior motor neuron (at the same time or in rapid
succession) for the threshold to be reached. This process
is called summation.
Uniform distribution of electrical potential inside the soma…
• Na+ spreads as a wave of depolarization through the soma cytosol(much like the ripples created by a stone tossed into a pond).
• The interior of the neuronal soma contains a highly conductive electrolyte
solution, the intracellular fluid, and has a large diameter (from 10 to 80 µm).
It causes almost no resistance to conduction of electric current.
• Therefore, any change in potential in any part of the intrasomal fluid causes
an almost exactly equal change in potential in all other points of the soma.
• This is an important principle because it plays a major role in “summation” of
signals entering the neuron from multiple sources.
If the wave is strong enough, and reaches the axon
hillock then this graded potential will lead to the
generation of the action potential.
If it does not reach the axon hillock, then the graded
potential will automatically die off and NO action
potential will be generated.
Question: The action potential does not occur adjacent
to the excitatory synapses. WHY?
Because the soma has relatively few voltage-gated sodium channels in its
membrane, while the membrane of the initial segment has 7 times the
conc. of these channels and, therefore, can generate an action potential
with much greater ease than can the soma.
If the wave is strong enough, and reaches the axon
hillock then this graded potential will lead to the
generation of the action potential.
If it does not reach the axon hillock, then the graded
potential will automatically die off and NO action
potential will be generated.
Question: The action potential does not occur adjacent
to the excitatory synapses. WHY?
What are the differences between Action and Graded Potential?
DIFFERENCES B/W GRADED & ACTION POTENTIAL
PROPERTY GRADED POTENTIAL ACTION POTENTIAL
Triggering eventStimulus by combination of NT
with receptor leading to change in permeability
Triggered by Dep. to threshold, usually by a graded potential or AP
Ion movement producingchange in Potential
Na+, K+, Cl- or Ca2+ by various means
Sequential movement of Na+
into & K+ out of the cell by voltage gated channels
Duration Varies with stimulus duration Constant
Direction of Pot. Change Can be Dep. Or Hyperpol. Always Depolarization
Location Usually dendrites & cell body Usually axon hillock & Trigger zone
Decremental in magnitude with distance
YES No
Summation YES NO
All or None Law NO YES
Refractory Period NO YES
Why doesn’t the discharge of a single synapse on the surface of a neuron almost never excites the
neuron?
The reason for this is that the amount of transmitter substancereleased by a single synapse causes an EPSP no greater than 0.5to 1 millivolt, instead of the 10 to 20 millivolts normally requiredto reach threshold for excitation.
Why doesn’t the discharge of a single synapse on the surface of a neuron almost never excites the
neuron?
PROPERTIES OF
SYNAPSES
1. DALE’S LAW:
This law states:
At a given chemical synapse only one type
of neurotransmitter is released and thus
only one effect, either excitatory or
inhibitory, is possible.
2. SYNAPTIC DELAY
Definition:
It is the time taken for the neurotransmitter
to be released from the presynaptic
membrane, diffuse across the synaptic
cleft to reach the post synaptic membrane
and bind to the neuroreceptors there.
It is about 0.5 msec.
3. ONE-WAY TRAVEL
In a chemical synapse the impulse always
travels in one direction only, from the
presynaptic to the postsynaptic cell. This is
because the neurotransmitter is only
released from the presynaptic terminal.
What happens when multiple synapses summate?
4. SUMMATION IN SYNAPSES
For each excitatory synapse that discharges simultaneously,
the total intrasomal potential becomes more positive by 0.5 to
1.0 mv.
When the EPSP becomes great enough, the threshold for
firing will be reached and an action potential will develop
spontaneously in the initial segment of the axon.
SPATIAL
SUMMATION
The effect of summing
simultaneous postsynaptic
potentials by activating
multiple terminals on
widely spaced areas of the
neuronal membrane
simultaneously is called
spatial summation.
By the process of
summation, the result is
greater than the strength
of a single synapse.
TEMPORAL
SUMMATION
Successive discharges
from a single presynaptic
terminal, if they occur rapidly
enough, can add to one
another; that is, they can
“summate.” This type of
summation is called temporal
summation.
By the process of summation,
the result is greater than the
strength of a single synapse.
5. CONVERGENCE
& DIVERGENCE
Usually the postsynaptic neuron receives afferents from a large number of neurons.
This means that a number of neurons will synapse on a single neuron. This is called Convergence.
It is very rare to find that only a single neuron synapses on another single neuron.
1:1 convergence is rare.
Same rules apply for Divergence.
6. Facilitation of neurons
Often the summated postsynaptic potential is excitatory but
has not risen high enough to reach the threshold for firing
by the postsynaptic neuron.
When this happens, the neuron is said to be facilitated.
Its membrane potential is nearer the threshold for firing
than normal, but not yet at the firing level.
Consequently, another excitatory signal entering the
neuron from some other source can then excite the neuron
very easily.
7. EFFECTS OF CHEMICAL CHANGES IN THE BLOOD:
• Acidosis depresses while alkalosis increases the
neuronal activity. (Thus, acidosis predisposes a
person to coma while alkalosis predisposes a
person to epileptic seizures.)
• Hypoxia exerts a depressing effect. (When
cerebral blood flow is interrupted even for a few
seconds, the person becomes unconscious.)
8. FATIGUE
Fatigue can occur due to the following reasons:
1. If there is continuous stimulation of the presynaptic synapse, this
leads to exhaustion or partial exhaustion of the neurotransmitter
stores. If all NT stores are depleted, the synaptic transmission may
stop.
2. Progressive inactivation of postsynaptic membrane receptors.
3. Slow development of abnormal conc. of ions inside the
postsynaptic neuron.
Question: What can be the advantage of fatigue?
When areas of the nervous system become overexcited, fatigue causes
them to lose the excess excitability after a while. E.g. during
epileptic seizure.
9. Effect of Drugs
• Caffeine, Theophylline and Theobromine all increase
neuronal excitability (by reducing the threshold for
neuronal excitation).
• Strychnine increases neuronal excitability (by inhibiting
the action of Inhibitory NT leading to severe tonic muscle
spasms.)
• Most anaesthetics decrease neuron excitability by
increasing the threshold for excitation.
NEUROTRANSMITTERS VS
NEUROMODULATORS
NEUROTRANSMITTERS
(Small Molecule, Rapidly
Acting Transmitters)
• Most acute responses.
• Synthesized in the cytosol of the
pre-synaptic terminal.
• Release and action of these
transmitters occur within a
milliseconds or less.
• Reuptake of the NT and/or its
components from the synaptic
cleft
• Reforming of the vesicles from
the membrane of the pre-
synaptic terminal membranes.
Neuropeptides, Slowly
Acting transmitters or
Growth factors
• Synthesized in the neuronal cell body
in a laborious process
• Much smaller quantities are usually
released as they are also much more
potent
• Prolonged action
• Some of their actions can be:
- prolonged closure of calcium channels
- prolonged changes in cell’s metabolic
machinery
- prolonged changes in
activation/inactivation of cell genes
- prolonged increase in excitatory/
inhibitory receptors
Some of the effects last for days, and
others for months or years.
Thus, neurotransmitters are involved in rapid
communication, whereas neuromodulators tend to be
associated with slower events such as learning,
development, motivational states, or even some
sensory or motor activities.