Synaptic Transmission

and Neurotransmitters
•What is synapse and synaptic transmission
•Types of synapses
•Structure that forms the synapse
• Process of synaptic transmission
•Properties of synapse
•How do synapses work
•Neurotransmitter release mechanism
•Types of neurotransmitter
•Dysfunction of synapses in brain

By Dr. Tambudzai Kanhema Jakobsen

[email protected]
Synaptic transmission-communication between
neurons
Neurons (also called neurones
or nerve cells) are the
fundamental units of the brain
and nervous system, the cells
responsible for receiving
sensory input from the
external world, for sending
motor commands to our
muscles, and for transforming
and relaying the electrical
signals at every step in
between.

More than that, their

interactions define who we are
as people.

Having said that, our roughly

100 billion neurons do interact
closely with other cell types,
 NEURON

•In the CNS, this other cell

is also a neuron.

• In the PNS, the other cell

may be either a neuron or
an effector cell
•e.g; gland or muscle

•A number of neurons are

involved in the transmission
of nerve impulse from its
origin to destination from
one neuron to another.
 NEURON STRUCTURE
 Axon
The long, thin structure in which action
potentials are generated; the transmitting part of
the neuron. After initiation, action potentials
travel down axons to cause release of
neurotransmitter.

 Dendrite
The receiving part of the neuron. Dendrites
receive synaptic inputs from axons, with the sum
total of dendritic inputs determining whether the
neuron will fire an action potential.

 Spine
The small protrusions found on dendrites that
are, for many synapses, the postsynaptic contact
site.
Steps of Synaptic Transmission

Action potential signal arrives at the presynaptic axon terminal

Opening of voltage gated Ca channels

Ca enters into the presynaptic terminal

Ca mediated exocytosis of neurotransmitter

Neurotransmitter binds to the receptors at post synaptic membrane

Opeining of ion channels

Movement of ions through the post synaptic membrane

Change in membrane potential in post synaptic membrane

Synaptic potential generated

 Action potentials and synapses
• Neurons communicate with each other via
electrical events called ‘action potentials’ and
chemical neurotransmitters.

• At the junction between two neurons

(synapse)an action potential causes neuron A
to release a chemical neurotransmitter.

• The (neurotransmitter)can either help (excite)

or hinder (inhibit) neuron B from firing its own
action potential.

• In an intact brain, the balance of hundreds of

excitatory and inhibitory inputs to a neuron
determines whether an action potential will
result.

• Action potential – Brief electrical event

typically generated in the axon that signals
the neuron as 'active'. An action potential
travels the length of the axon and causes
release of neurotransmitter into the synapse.
The action potential and consequent
transmitter release allow the neuron to
communicate with other neurons.
 Electric potential

The electric potential (also

called the electric field potential,
potential drop, the electrostatic
potential) is defined as the
amount of work energy needed
per unit of electric charge to
move this charge from a
reference point to the specific
point in an electric field.
 Membrane
potential

Membrane potential (also transmembrane potential or

membrane voltage) is the difference in electric potential between the
interior and the exterior of a neuron.

Membrane potential is a potential gradient that forces ions to

passively move in one direction: positive ions are attracted by the
'negative' side of the membrane and negative ions by the 'positive'
one.
 Synapse

A synapse is a
small gap at
the end of a
neuron that
allows a signal
to pass from
one neuron to
the next.

A junctions
between two
neurons
 Types of synapses

There are many kinds of

synapses within the
brain, they can be
divided into two general
classes:

 Electrical synapses

 Chemical synapses.
 Electric synapse

Membranes of the pre- and postsynaptic neurons come close

together and gap junctions form → low membrane borders
which allow passage of ions.

 Are less common than chemical synapses - Correspond to

gap junctions found in other cell types.
 The bidirectional transmission of electrical synapses permits
them to help coordinate the activities of large groups of
interconnected neurons.
 Promotes synchronous firing of a group of interconnected
neurons.
 (example in): mental attention, emotions and memory,
arousal from sleep.
 Electrical synapses are present throughout the CNS, smooth
and cardiac muscles, brain, and glial cells.
 GAP JUNCTIONS
 Adjacent cells electrically coupled through a channel.
 Each gap junction is composed of 12 connexin1 proteins
 Electric synapse
 Membranes of presynaptic and
postsynaptic cells are fused.

 Transmission is faster.

 Can be bidirectional.

 Generally associated with defensive

reflexes.
 Chemical synapse
•Almost all synapses in the CNS.

•First neuron secretes a chemical

substance called neurotransmitter at
the synapse to act on receptor on the
next neuron to excite it, inhibit or
modify its sensitivity).
•One direction transmission.
• NTs are released from synaptic
vesicles. - Vesicles fuse with axon
membrane and NT released by
exocytosis.

•Amount of NTs released depends upon

frequency of AP.
•Terminal bouton is separated from
postsynaptic cell by synaptic cleft. (20-
to 40-nanometer
Chemical synapse
SYNAPSES
Structure of the synapse

• Synaptic knobs
(presynaptic terminal):

• It has synaptic vesicles

(neurotransmitters).

• Synaptic cleft: It is the

space between the axon
terminal and
sarcolemma. It has a
width of 200-300
angstroms1

• Postsynaptic membrane:
It has receptors for
neurotransmitters or ion
channels.
Definition of synapse

•Definition: It is a junction where the

axon or some other portion of one cell
(presynaptic cell) terminates on the
dendrites, soma, or axon of another
neuron (postsynaptic cell).

• A connection between a neuron and a

second cell.

• - The CNS contains more than 100

billion neurons. The brain has 86 billion
neurons.

• - Some CNS neurons receive 20,000

synapses. - Synaptic input is converted
to a nerve impulse (AP) at the Axon
hillock2 .

• - The output signal (AP) travels by way

of a single axon leaving the neuron. -
 Function of
synapse

 The synapses determine

the directions that the
nervous signals will
spread through the
nervous system.

 -The synapses perform a

selective action, often
blocking weak signals
while allowing strong
signals to pass.
Anatomical types of Synapes

Dendrodendritic
(dendrite to dendrite)

Axosomatic
(synapse between the
axon of one neuron and
the soma of another)

Axodendritic
(synapse between the
axon of one neuron and
the dendritic of
another)

Dendrosomatic
Axoaxonic (dendrites to soma)
(axon to axon)
CHEMICAL SYNAPSE ELECRICAL SYNAPSE
Exhibits synaptic delay eg at NMJ reveal a delay Almost no delay in transmission
of 4.0 mili sec
20-40 nanometer distance that separates cells Cells approach within about 3.8 nm of each
other
Two separate cells that do not touch Gap junction are intercellular connection that
directly connect the cytoplasm
Slower than Electrical Faster: many neurons fire synchronously
Mostly unidirectional Mostly bidirectional

More complex behaviors Are fast, but can produce only simple behaviors

Act on receptors which are specific Without the need for receptors to recognize
chemical messengers

The response may not be the same as the The response is always the same sign as the
source source
The response in the postsynaptic neuron is Lack Gain the signal in the postsynaptic neuron
variable is the same or smaller than that of the
originating neuron
 Synaptic
Transmission
DEFINITION-
Neurotransmitter is a chemical
substance that acts as the
mediator for the transmission of
nerve impulses from one neuron
to another neuron through
synapse. It a messenger of
neurologic information from one
cell to another. 

HISTORY-
Evidence of neurotransmitter
was first discovered by an
Australian scientist named Otto
Loewi in 1921. He dreamt of an
experiment, which he did
practically and came out with
this discovery.
 Synaptic
transmission

The arrival of an action

potential at an axon

by Berton
Earnshaw
 Action potentials are propagated across the synapse by synaptic transmission, also known as
neurotransmission.

 The neuron that sends the signal is the presynaptic neuron, whilst the postsynaptic neuron
receives the signal.

 When the electrical impulse (action potential) reaches these synaptic vesicles, they release their
contents of neurotransmitters.

 Neurotransmitters then carry the signal across the synaptic gap. They bind to receptor sites on
the post-synaptic cell, thereby completing the process of synaptic transmission.
Criteria for neurotransmitter

To consider a substance as a
neurotransmitter, it should fulfill certain
criteria as given below

 The substance must be found in a neuron

1. It must be produced by a neuron

2. It must be released by a neuron

3. After release, it must act on a target area

and produce some biological effect.

4. After the action it must be inactivated

 How to define a neurotransmitter:

 Neurotransmitter must
be present at
presynaptic terminal.

 Neurotransmitter must
be released by
depolarization, Ca++
dependent.

 Specific receptors must

be present.
 Synaptic transmission

 A nerve impulse arrives.

 This causes calcium ion channels to

open, resulting in an influx of
calcium ions in the terminal.

 This causes synaptic vesicles to

fuse with the terminal membrane,
releasing neurotransmitter into the
gap between neurons, known as the
synaptic cleft.

 The neurotransmitters bind to

receptor sites on ion channels in the
postsynaptic membrane, causing
them to open.

 Ions flow into the postsynaptic

neuron, which generates an action
potential when a threshold level is
Neurotransmitters then carry the signal across
the synaptic gap.
They bind to receptor sites on the post-synaptic
cell, thereby completing the process of synaptic
transmission.

Pre-synaptic
Response A nerve impulse which begins as an
electrical signal in the presynaptic neuron, will be
translated chemically across the synaptic cleft by a
neurotransmitter.

Post-synaptic
Response Once the neurotransmitter binds to
receptors on the postsynaptic neuron, the message
becomes electrical once again.
This can result in either an excitatory postsynaptic
potential or an inhibitory postsynaptic potential.
Neurotransmitters are released by axonic end and
received on dendritic end.
The presynaptic terminal contains
large number of voltage-gated
calcium channels.

When an action potential

depolarizes the presynaptic
membrane, these Ca++ channels
open and allow large number of
calcium ions to flow into the
terminal.

▪ Quantity of neurotransmitter
substance is directly related to
number of calcium ions that inter.

▪ When calcium ion, they bind

with special protein molecules on
release sites allowing vesicles to
Mechanism of synaptic transmission

• Ca2+1 enters bouton down concentration gradient.

• Ca2+ activates calmodulin, which activates protein kinase. Protein

kinase1 aid in the fusion of synaptic vesicles3 .

• Binding to postsynaptic receptors (inhibition or excitation) of the

postsynaptic membrane (Depending on the type of the
neurotransmitter, i.e. excitatory or inhibitory).

• Information is transmitted in the central nervous system mainly in

the form of nerve action potentials, called Nerve impulses,
through a succession of neurons, one after another. - NT release is
rapid because many vesicles form fusion-complexes at “docking
site.”4
 Neurotransmitters
(Chemical Synapses)

 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:
Exitatory or inhibitory
Direct/ionotropic (open ion channels) or indirect/metabotropic
(active G-proteins) that create a metabolic change in the cell
CLASSIFICATION OF
NEUROTANSMITTERS
DEPENDING UPON CHEMICAL NATURE

 Amino Acids- The neurotransmitters of this group are

involved in fast synaptic transmission and are inhibitory
and excitatory in action. Eg. GABA, glycine, glutamate
and aspartate.

 Amines- Amines are the modified amino acids. The

neurotransmitters of this group involve in slow synaptic
transmission and are inhibitory and excitatory in action.
Eg. Noradrenaline, adrenaline, dopamine, serotonin and
histamine.

 Others- the one which do not fit in any of these

categories. Eg. Acetyl choline and nitric oxide.
 Neurotransmitters and their receptor
molecules
 Neurotransmitters only fits in one receptor

 Not all cells have receptors

 Neurotransmitters are excitatory in some cells and

inhibitory in other.

 Some neurotransmitters (noreoinephrine) attach

to the presynaptic terminals as well as
postsynaptic and then inhibit the release of more
neurotransmitters
 Excitatory Synapses

Excitatory synapse:

The release of an excitatory neurotransmitter (e.g.

glutamate) at the synapses will cause an inflow of
positively charged sodium ions (Na+) making a localized
depolarization of the membrane.

The current then flows to the resting (polarized) segment

of the axon.
Excitatory Neurotransmitters
 It is the chemical substance which is responsible for the
conduction of impulses from presynaptic neurons to post
synaptic neurons.

 The neurotransmitter released from the presynaptic axon

terminal does not cause development of action potential in
the post synaptic neuron.

 Rather, it causes some changes in the resting membrane

potential- slight depolarization by the opening of sodium
channels in the post synaptic membrane and the influx of
sodium ions from ECF.

 The slight depolarization is called excitatory post synaptic

potentials (EPSP).

 EPSP in turn causes development of action potential in the

initial segment of the axon of the postsynaptic neuron.

 The common excitatory neurotransmitters are

acetylcholine and noradrenaline.
 Amines
GROUP NAME SITE OF SECRITION ACTION
S
Amines Noradrenalin Postganglionic adrenergic sympathetic Excitatory
e nerve endings, cerebral cortex, and
hypothalamus, basal ganglia, brainstem Inhibitory
and spinal cord
Amines Adrenaline Hypothalamus, thalamus and spinal cord Excitatory
and
Inhibitory
Amines Dopamine Basal ganglia, hypothalamus, limbic Inhibitory
system, neo cortex, retina and synaptic
ganglia.
Amines Serotonin Hypothalamus, limbic system, cerebellum, Inhibitory
spinal cord, retina, GI tract, lungs and
platelets.
Amines Histamine Hypothalamus, cerebral cortex, GI tract Excitatory
and mast cells
 OTHERS
GROUPS NAME SITE OF ACTION
SECRITION

Others Nitric oxide Many parts of CNS, Excitatory

neuromuscular junction
and GI tract
Others Acetylcholi ne Pre ganglionic
parasympathetic nerve
endings Post ganglionic
parasympathetic nerve
endings Pre ganglionic Excitatory
sympathetic nerve
endings Post ganglionic
sympathetic cholinergic
nerve endings
Neuromuscular junction,
cerebral cortex,
hypothalamus, basal
ganglia, thalamus and
retin
 Inhibitory Synapses

Inhibitory
synapse
Inhibitory synapse: It causes an inflow of Cl- or outflow of
K+ making the synaptic membrane hyperpolarized.

This increase prevents depolarization, causing a decrease

in the possibility of an axon discharge. • If they are both
equal to their charges, then the operation will cancel itself
out.
Inhibitory Neurotransmitters:
It is the chemical substance which inhibits the conduction of
impulses from the presynaptic neuron to the postsynaptic
neuron.

 When it is released from the presynaptic axon terminal

due to the arrival of action potential, it causes opening of
potassium channels in the postsynaptic membrane and
efflux of potassium ions.

 This leads to hyperpolarization which is called inhibitory

postsynaptic potentials (IPSP).

 When IPSP is developed, the action potential is not

generated in the postsynaptic neuron.

 The common inhibitory neurotransmitters are gamma

amino butyric acid (GABA) and dopamine.
 Amino Acids
GROUPS NAME SITE OF SECRITION ACTION
Amino acids GABA Cerebral cortex, cerebellum, Inhibitory
basal ganglia, spinal cord and
retina
Amino acids Glycine Forebrain, brainstem, spinal Inhibitory
cord and retina
Amino acids Glutamate Cerebral cortex, brainstem and Inhibitory
cerebellum
Amino acids Aspartate Cerebellum, spinal cord and Inhibitory
retina
 Neurotransmitters

Several drugs act at this step of neurotransmission.

For example, some drugs that are given to Alzheimer’s patients work by inhibiting acetylcholinesterase
the enzyme that degrades acetylcholine.
This inhibition of the enzyme essentially increases neurotransmission at synapses that release
acetylcholine. Once released, the acetylcholine stays in the cleft and can continually bind and unbind to
 Synthesis and Storage of
Neurotransmitters
synaptic transmission.
Types of neurotransmitters
(eg acetylcholine, ACh) are synthesised in the axon, while others
(eg neuropeptides) are made in the cell body.

Acetylcholine –
This is synthesised within the synaptic terminal of the axon.
Its precursors (choline, acetate) are taken into the cell by membrane channels or created as by
products of other processes.
.
Enzymes (such as choline acetyltransferase) convert precursors into the neurotransmitter

Endogenous opioids (eg. enkephalins) –

These are an example of neuropeptides.
These large neurotransmitters are produced within the cell body via transcription in the nucleus and
translation in the endoplasmic reticulum.

Synthesised precursors are then packaged into secretory granules and sent to the axonal terminal.
Importantly, proteases present in the granules cleave the precursors into their mature neuropeptide
form during this journey.
 Postsynaptic
Receptors
The neurotransmitter in the synaptic cleft diffuses across the gap to the
post-synaptic membrane. Here, they can bind to two types of post-
synaptic receptors.

Name Inotropic receptors Metabotropic recepto

rs

Type Ligand-gated ion G protein-coupled

channels receptors
Response Channel Receptor acts
allows ion flux to through secondary m
change the cellular essengers to cause
voltage cellular effects
Speed of response Rapid Slow
Length of response Short-acting Prolonged response

This can cause either depolarisation to promote or hyperpolarisation to

inhibit the action potential generation in the post-synaptic neuron.
 Synthesis and Storage of
Neurotransmitters
After the synthesis the neurotransmitters are stored in
vesicles within the synaptic terminal until an action
potential arrives, causing their release.

Neurotransmitters such as acetylcholine are stored

within the small synaptic vesicles, whereas
neuropeptides reside within large dense-
core vesicles.
Inactivation of neurotransmitters
 After the execution of the action, neurotransmitter is inactivated by four
mechanisms:

1 It diffuses out of the synaptic cleft to the area where it has no

action.

2 It is destroyed or disintegrated by specific enzymes

3 It is engulfed and removed by astrocytes

4 It is removed by means of reuptake into the axon terminal.

 Fate of neurotransmitters

After a transmitter substance is

released at a synapse, it must be
removed by:

 Diffusion out of synaptic cleft

into surrounding fluid.

 Enzymatic destruction
 e.g (Ach esterase for Ach.)

 Active transport back into

presynaptic terminal itself e.g
norepinephrine.
Reuptake of
neurotransmitters

Reuptake is a process by
which the neurotransmitter is
taken back from synaptic
cleft into the axon terminal
after execution of its action.

The reuptake process

involves a specific carrier
protein for each
neurotransmitter.
 General function of synapses

 Neurotransmitter cycle in axon

Terminals
Synthesis
Storage
Release
Inactivation
Reuptake
Degradation

 Neural transmission problems

if cycle disrupted (eg., drugs)
at any step .
 Dysfunctional synapse

 Functional overview on the inhibitory

synapse with main proteins and pathways
affected in hyperekplexia, Down syndrome
(DS), and epilepsy.

 The major cause of hyperekplexia is

defective glycinergic signaling resulting
from mutations in genes involving subunits
of GlyRs, glycine transporter, or GlyR‐
interacting proteins.

 Excitation–inhibition imbalance underlies

deficient synapse function in epilepsy
and DS.

 In epilepsy, abnormal excitatory tonus

results from decreased GABA release and
concurrent enhanced glutamatergic
neurotransmission.

 In DS, an over‐inhibition of synapses by

Ecitatory synapse‐linked disease
mechanisms

Either increased or
decreased) function
of NMDA and AMPA receptor
s, disrupted mGluR
signaling and consequently
changes in long‐term
depression (LTD) are
postulated to play a crucial
role in the development
of ASD.
•Neuroregeneration
refers to the
regrowth or repair of
nervous tissues, cells
or cell products.
Peripheral
Neuropathy
THANK YOU