THE SYNAPSE

Defintion: site of contact between axon terminal of one neuron(presynaptic) with another neuron (postsynaptic) across which transmission of nerve impulses occur.
It could be electrical or chemical synapses.

Electrical synapse

rare in the nervous system.

the membranes of the presynaptic and postsynaptic neurons come close together forming areas of fusion called gap junction or tight junction, In these junctions the opposing membranes are held in position by connecting protein channels called connexon, which contain pores that permit ions to pass directly from one cell to the other.

Chemical synapse

Almost all synapses in the human central nervous system are chemical synapses. the impulses in the presynaptic axon causes secretion of a chemical transmitter at the synapse, and this transmitter act on receptors located in the membrane of the postsynaptic neuron to modify its activity either exciting or inhibiting it depending upon the nature of the postsynaptic receptors.

Structure of synapse

Structure of the synapse

In the synaptic bulb there are also many mitochondria (this suggests active transport is involved) Also present are synaptic vesicles These contain a neurotransmitter substance

The synapse
A place where two neurones functionally meet. Where they meet the neurones do not touch. There is a small gap, about 20nm wide The gap is called the synaptic cleft The neurone that carries the impulse to the synapse is called the presynaptic neurone The neurone that carries the impulse away is called the postsynaptic membrane

Synaptic transmission
When an AP arrives at a synaptic knob it causes calcium channels to open in the pre-synaptic membrane. Ca rushes into the synaptic bulb down its concentration gradient from the cleft.

Synaptic transmission
This influx of calcium ions causes vesicles containing acetylcholine to move towards the presynaptic membrane. The vesicles fuse with the membrane releasing the neurotransmitter into the synaptic cleft.

Synaptic transmission
The acetylcholine diffuses across the cleft and attaches to specific receptor sites on the postsynaptic membrane. The protein receptor sites have a complementary shape to that of acetylcholine but the binding is temporary

Synaptic transmission
The binding of the neurotransmitter to the receptor site opens up sodium channels in the postsynaptic membrane. Sodium ions flood in depolarising the membrane and set of an AP.

Synaptic transmission
The enzyme

acetylcholinesterase which is present in the synaptic cleft splits the acetylcholine into acetate and choline.

Synaptic transmission
The choline is taken back up by the synaptic knob and recombines with acetyl coenzyme A to reform acetylcholine.

Synaptic transmission
Hence the need for mitochondria in the synaptic knob. If the acetylcholine was not removed from the postsynaptic membrane it would keep firing action potentials!

Synaptic transmission

Neurotransmitters released at the synapse will lead to either

Excitation of the postsynaptic neurons: A.ch, noradrenaline and serotonin Inhibition of post synaptic neurons: GABA and glycin

Electrical events in synapse

Excitatory synapse:

permeability to all ions specially Na+

Depolarisation of postsynaptic neuron (EPSP) Localised, Last for 15msec. Several EPSP Action potential

Electrical events in synapse

Inhibitory synapse:

permeability to K+ (K+ outflux),CL- (CL- influx)

increases intracellular negativity

hyperpolaisation of postsynaptic neuron (IPSP)

EPSP vs. IPSP

EPSP:
Depolarization of the postsynaptic cell
excitatory effect

IPSP
Hyperpolarization of the postsynaptic cell
inhibitoryeffect

In CNS, often result of glutamate binding to AMPA receptors Excitatory synapses

Vesicles: round, uniform sizes Asymmetric synaptic densities

Often result of GABA (neurotransmitter) binding to its receptors Inhibitory synapses

Vesicles: flat, variable sizes, shaped Symmetrical densities Dont often occur in spines

When and IPSP and EPSP coincide, the EPSP is reduced and less likely to depolarize the membrane

Presynaptic inhibition

Inhibitory synaptic knob

Excitatory presynaptic neuron

Presynaptic inhibition

Central excitatory and central inhibitory state

Most synaptic neurons covered with thousand of synaptic knobs.

If a neuron at a given instant receives more excitatory impulses central excitatory state If a neuron at a given instant receives more inhibitory impulses central inhibitory state

Challenge question
See the picture below. If the following ion channels in the post-synaptic membrane are opened, will an IPSP or EPSP occur?

Characteristics of synaptic transmission

1. Forward conduction At synapse, the impulses can only pass in one direction from presynaptic to postsynaptic neuron..

2. Summation

Temporal summation

presynaptic cell

Temporal summation
low frequency of action potentials

presynaptic cell

Temporal summation
low frequency of action potentials

presynaptic cell

transmitter below threshold level

Temporal summation
low frequency of action potentials

presynaptic cell

transmitter below threshold level no depolarisation of postsynaptic cell

Temporal summation
low frequency of action potentials
high frequency of action potentials

presynaptic cell

transmitter below threshold level no depolarisation of postsynaptic cell

Temporal summation
low frequency of action potentials
high frequency of action potentials

presynaptic cell

transmitter below threshold level no depolarisation of postsynaptic cell

transmitter reaches threshold level

Temporal summation
low frequency of action potentials
high frequency of action potentials

presynaptic cell

transmitter below threshold level no depolarisation of postsynaptic cell postsynaptic cell depolarises

transmitter reaches threshold level

Spatial summation
A number of presynaptic neurones may converge on one postsynaptic neurone at the same time APs arriving in each presynaptic neurone will release transmitter, which builds up to the threshold level and triggers a postsynaptic impulse. This is called spatial summation

action potential only produced in one presynaptic cell

action potential only produced in one presynaptic cell

transmitter below threshold level

action potential only produced in one presynaptic cell

transmitter below threshold level

no depolarisation of postsynaptic membrane

action potential only produced in one presynaptic cell

action potential only produced in both presynaptic cells

transmitter below threshold level

no depolarisation of postsynaptic membrane

action potential only produced in one presynaptic cell

action potential only produced in both presynaptic cells

transmitter below threshold level

no depolarisation of postsynaptic membrane

transmitter reaches level

action potential only produced in one presynaptic cell

action potential only produced in both presynaptic cells

transmitter below threshold level

no depolarisation of postsynaptic membrane postsynaptic cell depolarises

transmitter reaches level

Characteristics of synaptic transmission

3. Synaptic delay

4. Synaptic fatigue

5. Factors affecting synaptic transmission

a. Effect of pH

Alkalosis
Acidosis

increases neuronal excitability.

depresses the neuronal excitability

b. Effect of hypoxia

c. Effects of drugs on the synapse

Nicotine: very similar affect to acetylcholine, has an excitatory effect on the postsynaptic membrane. In large concentrations it can block synaptic transmission after an initial stimulation

Effects of drugs on the synapse

Caffeine can cause an increase in the release of excitatory transmitter substances in the brain and has a mild stimulatory effect. theophyllin

Effects of drugs on the synapse

Opiates depress nerve transmission in sensory pathways of the spinal cord and brain that signal pain. This explains why opiates are such effective pain killers. Narcotics, anaesthetic drugs

Effects of drugs on the synapse

Both morphine and codeine are used as pain killer. The block the receptor sites in the post synaptic membrane.

6. Synaptic plasticity

is the ability of the synapse, between two neurons to change in strength in response to either use or disuse of transmission over synaptic pathway, ie, synaptic conduction can be strengthened or weakened on the basis of past experience. These changes are of great interest because they represent forms of learning and memory; these changes could be in the form of:
include synaptic potentiation, depression & sensitization.

A. Synaptic potentiation (facilitation):

This is production of enhanced (increased) PSPs. It occurs after applying a brief tetanizing train of stimuli to presynaptic neurons, and is 2 types:

1. Post-tetanic facilitation (Short-term potentiation)

When a presynaptic terminal is rapidly stimulated with successive stimuli, the postsynaptic neurone will show increase excitability for a period of seconds or minutes in some neurons Due to; Increase conc. of ca+ in the presynaptic neuron leading to more rapid release of the Nt

c. Long term potentiation: (LTP)

-more prolonged
- and can last for days. - initiated mainly by an increase of the intracellular calcium concentration in the postsynaptic neuron. -have an important role in learning and memory occurs in the hippocampus (where the excitatory neurotransmitter is glutamate).

b. Synaptic depression:

This is a decrease in the response of postsynaptic neurons, and is 2 types:

1. Habituation

When a stimulus is benign and is repeated over and over, the response to the stimulus gradually disappears (habituation). This is associated with decreased release of neurotransmitter from the presynaptic terminal because of decreased intracellular calcium.
which occurs secondary to inactivation of the Ca++ channels by an unknown mechanism).

2. Long term depression: (LTD)

- opposite of LTP; - it is characterized by a decrease in synaptic strength. -It is produced by slower stimulation of presynaptic neurons and is associated with a smaller rise in the intracellular calcium.

-due to dephosphorylation of post synaptic receptors.

c. Synaptic sensitization:

This is augmentation of a PSP in response to a habituated presynaptic stimulus, if it is paired once (or more times) with a noxious stimulus. and it occurs by a presynaptic facilitation mechanism as follows:

Cont. . Synaptic sensitization:

1. The noxious stimulus arrives via a facilitatory neuron which terminates on the preseynaptic ending.

2. The released transmitter from the facilitatory neuron (which is commonly serotonin) causes closure of the K+ channels in the presynaptic ending (which decreases K+ efflux).

cont.. Synaptic sensitization:

3. Due to reduction of the K+ efflux, presynaptic stimulation results in prolonged action potentials at its ending. This causes prolonged opening of the voltagegated Ca++ channels in the presynaptic ending, which leads to more Ca++ influx and, consequently, more release of the neurotransmitter (resulting in an augmented PSP).