The transmission of nervous impulses

and synaptic transmission

This presentation describes how nervous impulses are
transmitted along neurons and between neurons

Department of
Biochemistry

The transmission of nervous impulses and synaptic

transmission

Neurons transmit nervous impulses along

their axons
These nervous impulses are called action
potentials
Action potentials rely on the potential
difference across the membrane
In this presentation we will see how the
potential is generated and how synapses
function

Simplified

Myelin in the Peripheral and Central

Nervous Systems

In multiple sclerosis (MS), patches of myelin

are destroyed in the brain and spinal cord

Fig. 2-5, p. 32

Fig. 2-6, p. 33

Neurons can
synapse with:
1. Neurons

2. Muscle

3. Glands

Anatomical Types of Synapses

Figure 11.17

Functional Anatomy of a Synapse

CHEMICAL ACTIVITY AT SYNAPSE:

Typical neuron

Fig. 2.1 An example

of a neuron, or nerve
cell, showing several
of its important
features. The right
foreground shows a
nerve cell fiber in
cross section, and the
upper left inset gives
a more realistic
picture of the shape of
neurons. The nerve
impulse usually
travels from the
dendrites and soma to
the branching ends of
the axon. The neuron
shown here is a motor
neuron. Motor neurons
originate in the brain
or spinal cord and
send their axons to
the muscles or glands
of the body.

Typical neuron

Neurons
When the action potential reaches the axon
terminals it sends a signal to the next cell via a
synapse (see later) or similar structure.
This will result in
Muscle contraction
Hormone release
Change in activity of an organ e.g. heart
A signal being generated in the next neuron in the
pathway

Transmission of Nervous Impulses

The cell body
is stimulated
to the point
where it
generates an
action
potential

This is
transmitted
along the
axon

Impulses
jump across
the Schwann
cells via the
nodes of
Ranvier

This is called
saltatory
transmission
(saltere is
Latin for to
jump)

The Nerve Impulse

Resting Potential: Electrical charge of an

inactive neuron
Threshold: Trigger point for a neurons firing
Action Potential: Nerve impulse
Ion Channels: Axon membrane has these tiny
holes or tunnels
Negative After-Potential: When a neuron is
less willing to fire

Review of Solute Distribution in

Body Fluids
The [ ] gradient of K+
is the main source of
the membrane
potential
Change in
permeability ot Na+
can allow influx of
Na+
Depolarization
Electric signal
created
Controlled by
gated channels

Na+ Channels in Axon Have 2

Gates
Activation gate and
Inactivation gate
Na+ entry based on pos.
feedback loop needs
intervention to stop
Inactivation gates close in
delayed response to
depolarization
stops escalating pos.
feedback loop

Fig 8-10

Fig. 2.3 The inside of an axon normally has a negative electrical charge. The fluid surrounding an axon is
normally positive. As an action potential passes along the axon, these charges reverse, so that the interior of the
axon briefly becomes positive.

Fig. 2.4 Cross-sectional

views of an axon. The right
end of the top axon is at
rest, with a negatively
charged interior. An action
potential begins when the
ion channels open and
sodium ions (Na+) enter the
axon. In this drawing the
action potential would travel
rapidly along the axon, from
left to right. In the lower
axon the action potential has
moved to the right. After it
passes, potassium ions (K+)
flow out of the axon. This
quickly renews the negative
charge inside the axon, so it
can fire again. Sodium ions
that enter the axon during
an action potential are
pumped back out more
slowly. Their removal
restores the original resting
potential.

Potential difference
This is the difference in voltage between the
inside and outside of the cell as measured
across the cell membrane
It is around 70 mV (1 mV = 1/1000 Volt)
This is called the resting potential
You could measure this voltage with a sensitive
voltmeter

Membrane potential

Creating the potential

The potential is due to an imbalance of ions
across the cell membrane
Na+ ions are concentrated on the outside of the
cell K+ ions are concentrated on the inside of the
cell
This imbalance of charged particles (ions)
creates a potential difference
Other ions and proteins add to the potential
difference

Maintaining the potential

Ions are constantly pumped across the cell
membrane by ion pumps
The ion pumps are powered by ATP
Na+ ions are constantly pumped out of the
cell K+ ions are constantly pumped into the
cell
The imbalance of ions creates the
membrane potential

Pumping ions maintains the membrane

potential

The action potential I

This is a ripple of electrical activity on the cell
membrane of neurons
It stimulates a ripple of electrical activity in the
adjacent section of cell membrane
This stimulates a ripple of electrical activity in
the next section of cell membrane and so on
This ripple continues along the neuron - rather
like a Mexican wave

The nervous impulse is a series of action

potentials

The action potential II

Each action potential involves a reversal in the

polarity of the cell membrane
The inside of the cell is negative compared to the
outside when the cell is at rest
During the action potential, the inside of the cell
becomes positive and the outside negative
The polarity then returns to normal negative on
the inside and positive on the outside

The action potential III

The change in membrane potential is due to Na+ and K+
ions moving across the cell membrane
Firstly, Na+ moves into the cell and the inside of the
cell becomes more positively charged
Secondly, K+ moves out of the cell and the inside of
the cell becomes more negatively charged
After the action potential, the ion pumps return the
membrane to its normal resting potential

The movement of ions during

the action potential

Graph of Action Potential

Synaptic transmission
This presentation describes how nervous impulses
are transmitted between neurons
The process is quite complex but it is important to
understand it because the synapse is a target for
many common drugs

The synapse
Nervous impulses are transmitted from one neuron
to another via synapses
Synapses separate neurons by a small gap called
the synaptic cleft
Neurons communicate across the synaptic cleft
using neurotransmitters

The synapse

Structure of a synapse

How the synapse functions

1. The nervous impulse arrives at the terminal of a
neuron
2. Calcium ions enter the axon terminal
3. Neurotransmitters are released into the
synaptic cleft
4. Neurotransmitters bind to receptors on the postsynaptic membrane
5. The post-synaptic membrane is either stimulated
or inhibited

Animation of synaptic function

Neurotransmitters
Outside of the central nervous system (CNS) only
two neurotransmitters are found acetylcholine
and noradrenaline
In the central nervous system there are many
different neurotransmitters such as serotonin,
dopamine, glutamate, GABA etc.

NEUROTRANSMITTERS
IN
THE CENTRAL NERVOUS SYSTEM
Neurotransmitters of the central nervous system can be broadly
classified into two groups:

(i) Small- molecule neurotransmitters.

)

ii) Neuropeptides.

Small - Molecule Neurotransmitters

Rapidly acting, causing most of the fast responses of the
nervous system, such as transmission of sensory impulses to
the brain and motor signals to the muscles.
- Synthesized in the presynaptic terminals.
- Stored in vesicles in the presynaptic terminals.
- Released during the process of synaptic transmission to act on
the postsynaptic membrane receptors .

Small - Molecule Neurotransmitters

Class I
Acetylcholine
Class II (Biogenic Amines)
Dopamine
Norepinephrine
Serotonin
Histamine
Class III (Amino Acids)
Glutamate
Aspartate
- Aminobutyric acid (GABA)
Glycine
Class IV
Nitric oxide (NO)
Carbon monoxide (CO)

Acetylcholine :
- Synapses that release acetylcholine are known as cholinergic

synapses.
- These are widely distributed in the central nervous system .
- There are two types of receptors that can bind
acetylcholine:

1- Nicotinic Acetylcholine Receptors.

2- Muscarinic Acetylcholine Receptors.

1- Nicotinic Acetylcholine Receptors.

- These receptors are ligand- gated ionic channels.
- Once activated by binding with acetylcholine, the receptor
opens its gate to permit influx of Na+ ions, causing
depolarization in the postsynaptic membrane.

2- Muscarinic

Acetylcholine

Receptors

- Five types of muscarinic receptors have been identified (M1

to M5 receptors).
- All are G proteins coupled receptors.
- Activation

of

M1

receptors

closes

K+ channels causing

depolarization and excitation of the postsynaptic neuron

- Activation of M2

receptors causes opening of K+ channels

causing hyperpolarization and inhibition of the neuron.

Gs protein

closes

Depolarization

Small - Molecule Neurotransmitters

Class I
Acetylcholine
Class II (Biogenic Amines)
Dopamine
Norepinephrine
Serotonin
Histamine
Class III (Amino Acids)
Glutamate
Aspartate
- Aminobutyric acid (GABA)
Glycine
Class IV
Nitric oxide (NO)
Carbon monoxide (CO)

Dopamine
- Secreted as a transmitter by dopaminergic neurons, located
largely in the substania nirga of the midbrain, which project
their axons mainly to the basal ganglia.
- Five types of dopamine receptors have been identified (D1 to

D5 receptors), and all are acting through the G-proteins

second messenger system.
- Dopamine can produce either an excitatory or an inhibitory
effect depending upon the type of its postsynaptic receptor.

- The action of released dopamine is terminated mainly by its

rapid reuptake into the presynaptic terminal, where it is stored

once more in synaptic vesicles .

Norepinephrine
- Norepinephrine is secreted by noradrenergic neurons whose
cell bodies are located mainly in a region called the locus

ceruleus in the pons, from which the noradregnergic neurons

send nerve fibers both downward to the spinal cord , and

upward to widespread areas of the brain.

- The receptors for norepinephrine include both alpha () and

beta () adrenergic receptors. Both groups act through Gproteins, and there are multiple form of receptors in each group .

- In many of these areas,

norepinephrine appears to activate

excitatory receptors, but in some other areas it activates

inhibitory receptors.
- After dissociation from its receptor, most of the norepinephrine
is taken back into the presynaptic terminal where it is stored in
synaptic vesicles in preparation for release again into the synaptic
cleft
- One important function of epinephrine is to control the activity
of certain brain centers that play an important role in regulating
the psychological mood.

Serotonin
- Serotonin secreting neurons in the nervous system are located in
the raphe nuclei in the brain stem, which project their axons
to many areas in the brain and spinal cord.
- After dissociation from its receptor, most serotonin is
transported back into the presynaptic terminal by an active

reuptake mechanism
- Serotonin is involved in the activation of the pain control

system in the spinal cord, and its action in the higher regions of
the nervous system (the brain and brain stem) is believed to
control the mood of the person and plays a role in sleep .

Small - Molecule Neurotransmitters

Class I
Acetylcholine
Class II (Biogenic Amines)
Dopamine
Norepinephrine
Serotonin
Histamine
Class III (Amino Acids)
Glutamate
Aspartate
- Aminobutyric acid (GABA)
Glycine
Class IV
Nitric oxide (NO)
Carbon monoxide (CO)

Glutamate
- It is the most abundant excitatory transmitter in the nervous
system
- It is found in most areas of the brain and spinal cord .
- It activates ligand-gated cation channels, allowing increased
Na+ and Ca++ influx, thus causing excitation of the postsynaptic
neuron.

Gamma- Amino Butyric Acid (GABA):

- It is the major inhibitory transmitter in the brain
- It is a potent postsynaptic & presynaptic inhibitor
- GABA activates Cl- channels and K+ channels, allowing increased
Cl-

influx and increased K+ efflux. Both effects cause

hyperpolarization and inhibition of the postsynaptic neuron.

Glycine
- It is a neurotransmitter responsible for

direct inhibition

of synapses (postsynaptic inhibition).

- It is secreted by interneurons located in certain regions of the
brain stem and spinal cord.
- Glycine exerts its inhibitory effect by increasing Clconductance (Cl- flow currents) through a ligand - gated Cl-

channel in the postsynaptic membrane.

Neuropeptides
- Several families of peptides with relatively high molecular
weight whose actions are usually slow and prolonged.
- Synthesized in the soma of neurons rather than in the
synaptic terminal
- Stored within secretory vesicles that are then transported to
the nerve terminals by the mechanism of axonal streaming of
the axon cytoplasm.
- Examples: Substance P, Neuropeptide Y.

Prolonged effect on
calcium channels

Change in the number of

postsynaptic receptors

Synaptic control
Neurons in the CNS may synapse with many other
neurons
Some of these neurons will be excitatory
Some of these neurons will be inhibitory
This balance of excitation and inhibition allows for
very complex neuronal circuits

Synaptic Control

Drugs and the Nervous System

Understanding action potentials and synapses are
essential for understanding how some drugs work
This is covered more extensively in Principles of
Pharmacology
Most Mental Health drugs act on synapses in the brain
and alter the balance between excitation and
inhibition. The mechanism is complex
Let us look briefly at local anaesthetics

Local Anaesthetics

Local anaesthetics block Na+ channels in

neurons
How might this prevent the perception of
pain?

Local Anaesthetics
The action potential depends on Na+ entering the
cell
Blocking Na+ channels inhibits the action potential
Nervous impulses do not travel beyond the site of
anaesthesia
The brain is unaware of the pain stimulus

Synapses, Drugs and Addiction

The study of the influence of various kinds of

drugs has provided us with knowledge about

many aspects of neural communication at the
synaptic level.
Drugs work by mimicking our own
neurochemistry.
Example: receptors in the brain respond to LSD and

cocaine
Drugs alter various stages of synaptic processing.

Substance Abuse and Addictions

Addictive substances increase dopamine activity

in certain areas of the brain.

Olds and Milner (1954) placed rats in a Skinner
box that allowed self-stimulation of the brain by
the pressing of a lever.
Rats sometimes pressed the lever 2000 times per
hour to stimulated the release of dopamine in the
nucleus accumbens.

Substance Abuse and Addictions

Other behaviors that release dopamine include

sexual excitement, gambling, and video games.

fMRI research indicates dopamine is released
during viewing of attractive people.

Substance Abuse and Addictions

Berridge and Robinson (1998) suggest an

important distinction be made between liking

and wanting behaviors.
Activity in the nucleus accumbens seems to be
related to wanting.
Results in a monopolization of attention.

Drugs and the Synapse

Drugs either facilitate or inhibit activity at the

synapse.
Antagonistic drugs block the effects of

neurotransmitters.
Agonist drugs mimic or increase the effects of
neurotransmitters.

Drugs and the Synapse

Drugs work by doing one or more of the

following to neurotransmitters:

1.
2.
3.
4.
5.
6.

Increasing the synthesis.

Causing vesicles to leak.
Increasing release.
Decreasing reuptake.
Blocking the breakdown into inactive chemical.
Directly stimulating or blocking postsynaptic
receptors.

Drugs and the Synapse

A drug has an affinity for a particular type of

receptor if it binds to that receptor.

Can vary from strong to weak.

The efficacy of the drug is its tendency to

activate the receptor.

Drugs can have a high affinity but low efficacy.

Drugs and the Synapse

Almost all abused drugs stimulate dopamine

release in the nucleus accumbens,

small subcortical area rich in dopamine receptors
an area responsible for feelings of pleasure

Sustained bursts of dopamine in the nucleus

accumbens inhibit cells that release the

inhibitory neurotransmitter GABA

Drugs and the Synapse

Drugs are categorized according to their

predominant action or effect upon behavior

Stimulant drugs increase excitement, alertness,
motor activity and elevate mood.
Examples: amphetamines, cocaine,
methylphenidate (Ritalin), MDMA (Ecstasy),
nicotine

Drugs and the Synapse

Amphetamine stimulate dopamine synapses by

increasing the release of dopamine from the

presynaptic terminal.
Cocaine blocks the reuptake of dopamine,
norepinephrine, and serotonin.
Methylphenidate (Ritalin) also blocks the
reuptake of dopamine but in a more gradual and
more controlled rate.
Often prescribed for people with ADD

Drugs and the Synapse

MDMD (ecstasy) increases the release of

dopamine at low doses that account for its

stimulant properties.
Increases the release of serotonin at higher
doses accounting for its hallucinogenic
properties.
Research indicates damage to neurons that
contain serotonin.
Degree of risk to humans is not clear.

Drugs and the Synapse

Nicotine is the active ingredient in tobacco.
Nicotine stimulates one type of acetylcholine

receptor known as the nicotinic receptor.

Nicotinic receptors are found in the central
nervous system, the nerve-muscle junction of
skeletal muscles and in the nucleus accumbens.
Nicotinic receptors are also abundant in the
nucleus accumbens and facilitate dopamine
release.

Drugs and the Synapse

Opiate drugs are those that are derived from (or

similar to those derived from) the opium poppy.

Opiates decrease sensitivity to pain and increase
relaxation by attaching to endorphin receptors in
the brain.
Examples: morphine, heroin, methadone.

Drugs and the Synapse

The brain produces peptides called endorphins.
Endorphin synapses may contribute to certain

kinds of reinforcement by inhibiting the release of

GABA indirectly.
Endorphin synapses inhibit ventral tagmental
neurons that release GABA
Inhibiting GABA indirectly releases dopamine.

Drugs and the Synapse

Tetrahydocannabinol (THC) is the active

ingredient in marijuana.
THC attaches to cannabinoid receptors
throughout the brain but especially the cerebral
cortex, cerebellum, basal ganglia, and
hippocampus.
Anandamide and 2-AG are the endogenous
chemicals that attach to these receptors.

Drugs and the Synapse

The location of the receptors in the brain may

account for the subjective effects of loss of time,

an intensification of sensory experience, and also
memory impairment.
The cannabinoid receptors are located on the
presynaptic neuron and inhibit the release of
glutamate and GABA.

Drugs and the Synapse

Hallucinogenic drugs cause distorted perception.
Many hallucinogenic drugs resemble serotonin in

their molecular shape.

Hallucinogenic drugs stimulate serotonin type 2A
receptors (5-HT2A) at inappropriate times or for
longer duration than usual thus causing their
subjective effect.

Drugs

Main Behavioral
Effects

Main Synaptic
Effects

Amphetamine

Excitement, alertness,
elevated mood,
decreased fatigue

Increases release of
dopamine and several
other transmitters

Cocaine

Excitement, alertness,
elevated mood,
decreased fatigue

Blocks reuptake of
dopamine and several
other transmitters

Methylphenidate
(Ritalin)

Increased
concentration

Blocks reuptake of
dopamine and others,
but gradually

Drugs
MDMA (ecstasy)

Main Behavioral
Effects

Main Synaptic
Effects

Low dose: stimulant

Releases dopamine

Higher dose: sensory

distortions

Releases seratonin,
damages axons
containing seratonin

Nicotene

Mostly stimulant effects

Stimulates nicotinic-type
acetylcholine receptor,
which (among other
effects) increases
dopamine release in
nucleus accumbens

Opiates (e.g., heroin,

morphine)

Relaxation, withdrawal,
decreased pain

Stimulates endorphin
receptors

Drugs

Main Behavioral
Effects

Main Synaptic
Effects

Cannabinoids
(marijuana)

Altered sensory
experiences,
decreased pain and
nausea, increased
appetite

Excites negativefeedback receptors on

presynaptic cells;
those receptors
ordinarily respond to
anandamide and 2AG

Hallucinogens (e.g.,
LSD)

Distorted sensations

Stimulates seratonin
type 2A receptors (5HT2A)

End of Presentation

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