Neurophysiology

-Dr Sravanthi

OBJECTIVES

INTRODUCTION

NEURON AND TYPES

RESTING POTENTIAL

ACTION POTENTIAL

SYNAPSE AND TYPES

REFLEX ARC

NEUROTRANSMITTERS AND TYPES

NERVOUS SYSTEM

The Neuron

The nervous system is made of nerve

cells or neurons and glial cells. Glial

cells are not excitable and provide

metabolic and physical support for the

neurons. 90% of the cells are glial cells.

Neurons are excitable and control

behavior

STRUCTURE

TYPES

Ion channels

Resting potential

There is a potential

difference between the

inside and outside of

as membrane. The

inside is about -70 mv

relative to the outside.

Resting Potential

The resting potential is

caused by an uneven

distribution of ions

(electrically charged

molecules) of potassium

(K+) and sodium (Na+)

and chloride (Cl-).

This is caused by Na+/K+

ion pumps that move 3

Na+ ions out of the cell for

every 2 K+ ions it moves

in.

Therefore there are more

+ions outside the cell than

inside and the inside is

negatively charged with

respect to the outside

Ion pump

Resting potential

Forces maintaining the resting potential

Diffusion pressure – molecules want to move

from areas of high concentration to areas of

low concentration.

Electrostatic charge – ions with like charge

are repelled and ions with a different charge

are attracted.

Operation of ion pumps and ion channels.

Action potential

Anything that alters the functioning of the ion

channels can change the resting potential.

If changes cause the resting potential to be

reduced, this is called depolarization.

If the change causes an increase in the resting

potential, this is caused hyperpolarization.

Action potential

ACTION POTENTIAL 1.AP, activation of the voltage-dependent

Na+ channels (soma, area of the initial

segment)

2. ADP, after-depolarization, acctivation of

a high threshold Ca2+ channels, localized

in the dendrites

3.AHP, after-hyperpolarization, Ca2+

sensitive K+ channels

4.Rebound depolarization, low threshold

Ca2+ channels, de-inactivated during the

AHP, activated when the depolarization

decreases (probably localized at the level

of the soma

Action potential

Voltage gated ion channels open and let Na+ into the cell. They are driven into the cell because of diffusion gradient and electrostatic charge.

This causes the resting potential to reverse, i.e., the inside the cell becomes positive.

Now the Na+ ion channels close and the K+ channels open and the K+ ions are driven out of the cell because of their concentration gradient and electrostatic charge.

Finally the K+ channels close and the ion pumps kick in and the resting potential returns to normal.

All or None Law

Action potentials when they occur are

always the same.

Once the process is initiated, it must run

its course and nothing can stop it or

change it

Transmission of action potentials

along a membrane

When an action potential occurs at one

place on the membrane of an axon, the

surrounding membrane is depolarized past

threshold causing an action potential. This

depolarizes the neighboring membrane,

etc.

Action potentials sweep across a

membrane as fast as 100m/sec

Transmission of action potentials

along a membrane

SYNAPSE

A junction that mediates information

transfer from one neuron:

To another neuron

To an effector cell

Presynaptic neuron – conducts impulses

toward the synapse

Postsynaptic neuron – transmits impulses

away from the synapse

Junction between two cells

Site where action potentials in one cell

cause action potentials in another cell

Types of cells in synapse

Presynaptic

Postsynaptic

TYPES a)axosomatic

b)axodendritic

c)axoaxonic

TYPES: A)CHEMICAL

SYNAPSE Components

Presynaptic terminal

Synaptic cleft

Postsynaptic membrane

When an action potential arrives at the terminal

bouton, it causes Ca++ channels to open.

This causes the vesicles to move to the membrane and release a chemical called a neurotransmitter to be released into the synaptic cleft.

The neurotransmitter diffuses across the cleft and activates receptors on the postsynaptic membrane which cause changes on the resting potential by altering the functioning of ion channels.

B)ELECTRICAL SYNAPSE

Synapse

Any neuron can have thousands of synapses on it

Postsynaptic potentials

The membranes of dendrites and cell

bodies do not have action potentials.

Instead, any depolarizing stimulus causes

a post synaptic potential (PSP) which

spreads out across the membrane. The

depolarization is weaker the further it gets

from the stimulus. When the stimulus is

turned off, the PSP disappears.

Postsynaptic potentials

Postsynaptic potentials can either be excitatory (depolarization) or inhibitory.

Excitatory and inhibitory potentials can summate both in time (temporal summation) and across the membrane (spatial summation) .

The net effect of summation is reflected at the axon hillock where action potentials are generated.

Post synaptic potential

The change in the resting potential caused by the activation of a receptor site is called the post synaptic potential (PSP).

IPSP – when the change causes hyperpolarization or makes the cell harder to fire, this is called an inhibitory post synaptic potential.

EPSP – when the change causes depolarization, this is called an excitatory post synaptic potential.

RESTING,EXCITED,INHIBITED

NEURON

Post synaptic potential

The excitation and inhibition caused by all

the active synapses on the dendrites and

cell body are summed and the net effect

is reflected in the rate at which the axon

hillock generates action potentials

Summation

SUMMATION

Dale’s Law

A single neuron always produces the same

transmitter at every one of its synapses.

It is now known that the law is not always right.

Terminating synaptic action

Once the neurotransmitter is released into

the cleft, there must be a means by which

its activity is terminated. This can be

accomplished two ways

The neurotransmitter can be destroyed by an

enzyme in the cleft

The neurotransmitter can be reabsorbed back

into the bouton (reuptake).

NEUROTRANSMITTER

REMOVAL

Proteins

Ion pumps, ion channels, etc., are large

molecules of protein.

Proteins are long strings of amino acids that can

fold into many three dimensional shapes. The

same protein can have different configurations,

i.e., they can change shape.

Receptors are protein molecules that change

shape (are activated) by neurotransmitter

molecules with a particular shape.

Receptors

Receptor sites can be

part of an ion channel

and when the

receptor site is

occupied by a

neurotransmitter, the

ion channel opens

Reflex arc

Knee-jerk reflex

COMPONENTS

Research on reflexes

Sir Charles Scott Sherrington

Great Britain

nobelist 1932

Ivan Petrovich Pavlov

Russia

nobelist 1904

Behavior as a chain of reflexes?

LOCUST

Two pairs of wings

Each pair beat in

synchrony but the rear

wings lead the front wings

in the beat cycle by about

10%

Proper delay between

contractions of the front

and rear wing muscles

Second messenger cascade

Second messenger molecules can activate a kinase which lasts for minutes and hours.

Kinases can activate transcription factors (CREB and c-fos) which alter the expression of genes.

Genes carry the codes for the creation of proteins including ion channels and receptor sites and this can cause permanent changes in synaptic function.

autoreceptors

The membrane of the presynaptic cell has

many receptor sites which detect the

neurotransmitter. This is a feedback

system which regulated the amount of

neurotransmitter released into the cleft

Other signaling between neurons

Neuromodulators are chemicals that can alter the effect of a neurotransmitter.

Sometimes the postsynaptic membrane releases molecules that affect the presynaptic membrane.

DSE- depolarization-induced suppression of excitation

DSI – depolarization-induced suppression of inhibition.

Axo-axonal synapses: axons may also have synapses

NEUROTRANSMITTERS

Chemicals used for neuronal communication

with the body and the brain

50 different neurotransmitters have been

identified

Classified chemically and functionally

Chemically:

• ACh, Biogenic amines, Peptides

Functionally:

• Excitatory or inhibitory

• Direct/Ionotropic (open ion channels) or

Indirect/metabotropic (activate G-proteins) that

create a metabolic change in cell

types

EXCITATORY

Acetylcholine

Aspartate

Dopamine

Histamine

Norepinephrine

Epinephrine

Glutamate

Serotonin

INHIBITORY

GABA

Glycine

CHEMICAL-NT’S

Acetylcholine (ACh)

Biogenic amines

Amino acids

Peptides

Novel messengers: ATP and dissolved

gases NO and CO

BIOGENIC-NT’S

Include:

Catecholamines – dopamine, norepinephrine

(NE), and epinephrine (EP)

Indolamines – serotonin and histamine

Broadly distributed in the brain

Play roles in emotional behaviors and our

biological clock

AMINO ACID-NT’S

Include:

GABA – Gamma ()-aminobutyric acid

Glycine

Aspartate

Glutamate

Found only in the CNS

PEPTIDES-NT’S

Include: Substance P – mediator of pain signals

Beta endorphin, dynorphin, and enkephalins

Act as natural opiates, reducing our perception of pain Found in higher concentrations in marathoners and

women who have just delivered

Bind to the same receptors as opiates and morphine

Neurohormones

Substances that act at neuron receptor

sites, but are not specific to an individual

synapse.

May be released far from the synapse.

Act as a neuromodulator (modify the

activity of a neurotransmitter)

NOVEL MESSENGERS-NT’S

Nitric oxide (NO)

A short-lived toxic gas; diffuses through post-synaptic

membrane to bind with intracellular receptor

(guanynyl cyclase)

Is involved in learning and memory

Some types of male impotence treated by stimulating

NO release (Viagra)

• Viagra NO release cGMP smooth muscle relaxation

increased blood flow erection

• Can’t be taken when other pills to dilate coronary b.v. taken

Carbon monoxide (CO) is a main regulator of

cGMP in the brain

Drugs mostly act on the nervous system by

interacting with neurotransmission,

They may:

act on receptor sites and cause the same effect as a

transmitter: agonism

block a receptor site: antagonism

decreasing activity of enzymes that destroy a

transmitter

block reuptake mechanisms

blocking ion channels

altering release of transmitter

altering the action of neurohormones

Synapses that use NE are nor adrenergic (remember,

adrenaline is another word for epinephrine)

DA are dopaminergic

5-HT are serotonergic

ACh are cholinergic

etc

Acetylcholine:

Broken down by AchE (acetylcholinesterase)

Receptors: nicotinic and muscarinic

Stimulated Blocked Function

nicotinic nicotine curare Voluntary muscle control

(neuromuscular junctions)

muscarinic muscarine atropine Involuntary muscle control

botox and nerve gasses

Biogenic amines

Serotonin, Dopamine Norepinephrine and

Epinephrine

Broken down by MAO and COMT

Reabsorbed by transporter mechanisms

Influenced by amphetamines and cocaine and SSRIs and

SNRIs

E and NE receptor sites alpha (α)and Beta (β) with

subtypes 1 and 2

DA has 6 receptor subtypes D1 and D2....D6 with sub sub

types a b c, etc

Serotonin has 4 main receptor subtypes with sub sub

types a b c etc.

GABA

Universally inhibitory transmitter

Opens a Chloride ion channel which stabilizes the

membrane and makes it harder to depolarize

Drugs like benzodiazepines enhance the ability of GABA

to open the ion channel.

There are two types of GABA receptors; GABAA and

GABAB.

There are many different subtypes of GABAA receptors

which control different functions.

GABAB receptors are less common and use a second

messenger

GABA

Glutamate

excitatory transmitter

NMDA receptor open ion channel and lets +ions

into the cell

the channels can be blocked by alcohol, solvents

and some hallucinogens

Peptides

opioid type peptides

enkephalins (5 amino acids)

endorphines (16 to 30 amino acids)

Receptor subtypes mu, kappa and delta

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