The cholinergic synapse and the roles of synapses

1Why some pesticides are so dangerous

Many insecticides sprayed on crops belong to a group called organophosphates. They kill insects by jamming one enzyme at their synapses. The same enzyme does the same job in human synapses, which is why a careless farmer who breathes in the spray or spills it on the skin may suffer twitching, sweating, a slow heartbeat and difficulty breathing. To understand both the poisoning and how our nervous system works normally, we need to look at the tiny gap between two neurones: the synapse.

2Structure of a cholinergic synapse

3Transmission across a cholinergic synapse

1. An action potential arrives at the synaptic knob and depolarises the presynaptic membrane.
2. Voltage-gated Ca²⁺ channels open and calcium ions diffuse into the knob from the tissue fluid.
3. The rise in Ca²⁺ makes synaptic vesicles move to the presynaptic membrane and fuse with it, releasing acetylcholine into the cleft by exocytosis.
4. ACh diffuses across the cleft and binds to the receptor proteins on the postsynaptic membrane.
5. Binding opens the receptors' Na⁺ channels. Na⁺ diffuses into the postsynaptic neurone and depolarises it. If the depolarisation reaches threshold, an action potential starts in the postsynaptic neurone.
6. Acetylcholinesterase hydrolyses ACh into choline and ethanoic acid, so the receptors are freed and the Na⁺ channels close. Without this step the postsynaptic neurone would go on firing.
7. Choline and ethanoic acid diffuse back into the synaptic knob, where they are recombined into ACh using ATP from the many mitochondria, and packed into vesicles again. Ca²⁺ is pumped out of the knob.

The whole sequence causes a synaptic delay of about 0.5 ms at each synapse, mostly the time for exocytosis and diffusion.

4The roles of synapses

Synapses slow impulses down slightly, yet every nervous system is built of them, because they do jobs that a continuous network of axons could not:

• They make impulses travel in one direction. Only the presynaptic knob has vesicles of neurotransmitter, and only the postsynaptic membrane has receptors.
• Summation filters out weak signals. One presynaptic impulse often releases too little ACh to bring the postsynaptic neurone to threshold. In temporal summation, several impulses arrive in quick succession along one neurone; in spatial summation, impulses arrive at the same time from several presynaptic neurones. Their effects add up, so only a strong or repeated stimulus gets through, and low-level "background noise" is ignored.
• Inhibition. At inhibitory synapses, the transmitter opens channels that let Cl⁻ in or K⁺ out, so the postsynaptic membrane is hyperpolarised and harder to excite. This lets the brain cancel or block signals; for example, when you hold a hot plate you mean to carry, inhibition stops the withdrawal reflex.
• Convergence and divergence. Many neurones can converge on one (as rods do in the retina, giving sensitivity), and one neurone can diverge to many, spreading a signal to several parts of the body or brain.
• Protection from overstimulation. With very repetitive stimulation, transmitter is released faster than it can be remade and the synapse stops passing impulses (synaptic fatigue).
• Learning and memory. Synapses that are used often become stronger and new synapses form, which is believed to be the cellular basis of learning and memory.

5The neuromuscular junction

A motor neurone makes a special cholinergic synapse with a muscle fibre, the neuromuscular junction. The postsynaptic membrane, the motor end plate, is deeply folded to hold many receptors, and the junction is always excitatory: every impulse that arrives releases enough ACh to trigger an action potential in the muscle fibre, so there is no summation.