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.