Synaptic Transmission

Synapses allow signals to be transmitted between neurones, or between a neurone and an effector. The signal crosses the synaptic cleft as a chemical message — a neurotransmitter.

• A synapse between two neurones that uses acetylcholine (ACh) as the neurotransmitter is called a cholinergic synapse.
• A synapse between a motor neurone and a muscle fibre is called a neuromuscular junction.

Structure of a Synapse

A synapse is the junction between two neurones, or between a motor neurone and an effector.

• Synaptic cleft — the tiny gap between the presynaptic and postsynaptic membranes.
• Presynaptic neurone — has a swollen ending called the synaptic knob, which contains synaptic vesicles filled with neurotransmitter. The synaptic knob also contains many mitochondria (to provide ATP for neurotransmitter synthesis and active transport).
• Postsynaptic membrane — has specific receptors that the neurotransmitter binds to.
• There are many different neurotransmitters. Synapses that use acetylcholine (ACh) are called cholinergic synapses.

Transmission Across a Cholinergic Synapse

1. An action potential arrives at the synaptic knob of the presynaptic neurone.
2. This causes voltage-gated calcium ion (Ca²⁺) channels in the presynaptic membrane to open.
3. Ca²⁺ ions diffuse into the synaptic knob down their concentration gradient.
4. The influx of Ca²⁺ causes synaptic vesicles to move to the presynaptic membrane and fuse with it.
5. The vesicles release ACh into the synaptic cleft by exocytosis.
6. ACh diffuses across the synaptic cleft and binds to specific receptors on the postsynaptic membrane.
7. This causes sodium ion (Na⁺) channels in the postsynaptic membrane to open (these open because ACh has bound to them).
8. Na⁺ ions diffuse into the postsynaptic cell, causing depolarisation of the postsynaptic membrane.
9. If the depolarisation reaches the threshold, an action potential is generated in the postsynaptic neurone.
10. Acetylcholinesterase (AChE), an enzyme in the synaptic cleft, breaks down ACh (hydrolyses ACh). This stops the signal and prevents continuous stimulation.
11. Ca²⁺ ions are actively transported back out of the synaptic knob.

Why is transmission unidirectional?

• Neurotransmitter vesicles are only found in the presynaptic neurone, so neurotransmitter can only be released from the presynaptic side.
• Receptors for the neurotransmitter are only on the postsynaptic membrane.
• So the signal can only travel in one direction across the synapse.

Excitatory and Inhibitory Synapses

• Excitatory synapses — the neurotransmitter causes depolarisation of the postsynaptic membrane, making it more likely to reach threshold and fire an action potential.
• Inhibitory synapses — the neurotransmitter causes hyperpolarisation of the postsynaptic membrane (the potential difference becomes more negative than the resting potential), making it less likely to fire an action potential.

Summation

Summation is the process by which the effects of multiple small depolarisations are added together to reach the threshold for an action potential. A single impulse may not release enough neurotransmitter to reach threshold on its own.

Spatial summation

• Multiple presynaptic neurones all connect to one postsynaptic neurone.
• They release neurotransmitter at the same time, and the combined depolarisation may be enough to reach the threshold.
• Some of these synapses may be inhibitory — if enough are inhibitory, the overall effect may not reach threshold, and no action potential is fired.

Temporal summation

• One presynaptic neurone fires multiple impulses in quick succession.
• Neurotransmitter accumulates in the synaptic cleft faster than it can be broken down by AChE.
• The combined effect of repeated neurotransmitter release may be enough to reach the threshold and trigger an action potential.

Cholinergic Synapse vs Neuromuscular Junction

A neuromuscular junction (NMJ) is the synapse between a motor neurone and a muscle fibre (effector). It uses the same basic mechanism as a cholinergic synapse, but with some key differences:

• The neurotransmitter is ACh (same as a cholinergic synapse).
• The postsynaptic membrane (called the motor end plate) has junctional folds — these increase the surface area for more ACh receptors and more AChE.
• An NMJ is always excitatory — it always triggers muscle contraction. A cholinergic synapse can be either excitatory or inhibitory.

Animation below shows the action at a neuromuscular junction (you should be able to notice a few differences between the cholinergic synapse, especially at the end)

Effects of Drugs on Synapses

You don’t need to memorise specific drugs, but you do need to predict and explain the effect of a drug from a description of how it works.

Types of drug action

• Agonists — have a similar shape to the neurotransmitter, so they bind to and activate the postsynaptic receptors. Effect: the postsynaptic neurone is stimulated even without a nerve impulse, so the response is enhanced/continuous.

• Antagonists — bind to the postsynaptic receptors but do not activate them, blocking the neurotransmitter from binding. Effect: the postsynaptic neurone is not stimulated, so transmission is blocked.

• Inhibitors of neurotransmitter breakdown — prevent the enzyme (e.g. AChE) from breaking down the neurotransmitter. Effect: neurotransmitter remains in the synaptic cleft for longer, so the postsynaptic membrane is stimulated repeatedly/for longer.

• Drugs that stimulate neurotransmitter release — cause more neurotransmitter to be released from the presynaptic neurone. Effect: more neurotransmitter in the synaptic cleft, so more receptors are activated and the response is enhanced.

Try it: Drug Effect Simulator