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Biology › Nervous coordination, receptors, muscles and behaviour › The synapse: a gap that makes the whole system one-way

The synapse: a gap that makes the whole system one-way

Every impulse ends at a gap 20 nm wide that it cannot cross. What crosses is a chemical, released on one side and detected on the other, and that asymmetry is what turns a mass of connected neurones into a system with a direction.

Before this The action potential and the refractory period · Exocytosis and membrane-bound receptor proteins

Before you start

The impulse crosses the synapse. Almost every rough answer says something like it, and the truth is stranger and more useful: the impulse arrives at the presynaptic membrane and stops there. Nothing electrical goes any further. A chemical is released, drifts across a gap about 20 nm wide by diffusion, and binds to the far side, where — if enough of it arrives — an entirely new action potential begins in a different cell. The message continues; the impulse does not.

What you should be able to do

What is actually there

A synapse is the junction between two neurones, or between a neurone and an effector. The one worth knowing in detail is the cholinergic synapse, which uses acetylcholine as its neurotransmitter and appears at neuromuscular junctions and throughout the nervous system.

The axon of the presynaptic neurone ends in a swelling, the synaptic knob. It is packed with mitochondria and with vesicles of acetylcholine, and its membrane carries voltage-gated calcium channels. Across a synaptic cleft of about 20 nm sits the postsynaptic membrane, whose receptor proteins have binding sites complementary to acetylcholine and which are themselves sodium channels.

Two details of that description do the work later. The vesicles are only on the presynaptic side. The receptors are only on the postsynaptic side. Everything about the direction of a nervous system follows from those two facts.

Seven steps, numbered in the order they occur. Steps 1 to 3 happen on the presynaptic side, 4 in the cleft, 5 and 6 on the postsynaptic membrane, and 7 clears up so that it can all happen again.
Synapse
The junction between the end of one neurone and another neurone or an effector cell, across which chemical transmission occurs.
Neurotransmitter
A chemical released from a presynaptic neurone that diffuses across the cleft and binds to receptors on the postsynaptic membrane.
Cholinergic synapse
A synapse that uses acetylcholine as its neurotransmitter.
Excitatory postsynaptic potential
A depolarisation of the postsynaptic membrane that makes an action potential more likely.

The sequence, in the order marks are given for it

Learn this as a sequence rather than as a list of facts; questions almost always ask you to describe it, and a step out of order costs the mark.

The action potential arrives at the synaptic knob and depolarises its membrane. Voltage-gated calcium channels open, and calcium ions diffuse into the knob from the cleft, where their concentration is much higher.

The influx of calcium causes vesicles of acetylcholine to move to the presynaptic membrane and fuse with it, releasing their contents into the cleft by exocytosis. Acetylcholine then crosses the cleft by diffusion — no pumping, no energy, just a 20 nm journey down a concentration gradient, which takes well under a millisecond.

On the far side, acetylcholine binds to receptor sites on the postsynaptic membrane. The receptors are sodium channels, and binding changes their shape so that they open. Sodium ions diffuse into the postsynaptic neurone and depolarise it, producing an excitatory postsynaptic potential. If enough receptors are occupied for the membrane to reach threshold, voltage-gated sodium channels open and a new action potential begins.

Then the cleft is cleared. Acetylcholinesterase, an enzyme in the cleft, hydrolyses acetylcholine into choline and ethanoic acid. The products are reabsorbed into the presynaptic knob and recombined into acetylcholine using ATP from those mitochondria, and the vesicles are refilled.

That last step is not housekeeping. Without it, acetylcholine would stay bound to the receptors, the sodium channels would stay open, and the postsynaptic membrane would keep firing — which is exactly what certain poisons do, as the last section shows.

Putting a delay to work

Transmission across one synapse takes roughly 0.7 ms. A reflex pathway contains two synapses, and the total time from stimulus to response is 30 ms. What fraction of the delay is synaptic, and what does that imply about a pathway routed through the brain instead?

Two synapses at 0.7 ms give about 1.4 ms of synaptic delay, which is 1.4 ÷ 30 ≈ 0.047, so under 5% of the total. Most of the 30 ms is conduction along the neurones.

The implication is about scale rather than about this number. A conscious response involves many neurones in the brain and therefore many more synapses; adding a hundred of them would add about 70 ms on its own, before any of the extra conduction distance is counted.

This is why a reflex arc is built the way it is. Each synapse buys something — a junction where signals can be combined, blocked or redirected — and a pathway that needs speed above all else buys as few of them as it can.

Why it only goes one way

Neurones are wired into networks with branches everywhere, so something has to stop impulses running backwards through them. The synapse does it, and the explanation is structural rather than clever.

Vesicles of neurotransmitter are found only in the presynaptic knob, so acetylcholine can only be released on that side. Receptors are found only on the postsynaptic membrane, so acetylcholine can only be detected on the other. An impulse arriving at the postsynaptic side of a synapse finds nothing to release and nothing on the far side to detect it.

This gives the nervous system a direction, which in turn allows a reflex arc to run reliably from receptor to effector, and allows a network to have inputs and outputs rather than simply resonating. The refractory period keeps an impulse travelling one way along an axon; the synapse keeps it going one way between axons. Different mechanisms, same effect, and questions sometimes ask for both.

Summation and inhibition

One impulse arriving at one synapse rarely triggers anything. Each vesicle releases a fixed quantity of acetylcholine, and a single excitatory postsynaptic potential is typically a few millivolts against the 15 mV needed to reach threshold from −70 mV. Postsynaptic neurones add contributions together, and there are two ways of doing it.

The left panel is what one impulse achieves on its own: not enough. The middle and right panels reach the same total by different routes, and the letters underneath are what distinguishes them.

Spatial summation adds inputs from different presynaptic neurones arriving at the same postsynaptic cell at the same time. Several small depolarisations together take the membrane past threshold. This is the mechanism behind rod convergence in the retina, and it is how a postsynaptic neurone can respond to a pattern of inputs rather than to any one of them.

Temporal summation adds impulses from a single presynaptic neurone arriving in quick succession. The transmitter from the first has not yet been cleared when the second arrives, so the depolarisations build on one another. High-frequency firing therefore gets through where the same number of impulses spread over a longer time would not — which is one more reason frequency is a usable code.

Not every synapse is excitatory. At an inhibitory synapse the receptors open chloride channels, letting negative chloride ions in, or potassium channels, letting positive potassium ions out. Either way the postsynaptic membrane becomes more negative — hyperpolarised — so a larger excitatory input is now needed to reach threshold. Inhibition is not a fault or a failure; it is how the nervous system sharpens signals, suppresses unwanted movements and stops everything firing at once.

Where drugs act

Almost every drug that affects the nervous system works at a synapse, and there are only a handful of ways to interfere with one. Questions in this area give you an unfamiliar substance and expect you to reason about it from the sequence, so it pays to know the categories with an example of each.

DrugWhat it doesEffect
NicotineBinds to acetylcholine receptors and activates themPostsynaptic neurone depolarised as though ACh had bound: more impulses
Organophosphate insecticidesInhibit acetylcholinesteraseACh is not broken down, receptors stay occupied, continuous firing
CurareBlocks acetylcholine receptors without activating themACh cannot bind, no depolarisation, muscles are paralysed
CocaineBlocks reuptake of dopamine from the cleftDopamine stays in the cleft and keeps binding, so the synapse fires repeatedly
Botulinum toxinPrevents vesicles releasing acetylcholineNo transmitter released, no depolarisation, muscles cannot contract

Two of those are worth reading twice, because they look similar and do opposite things. Nicotine and curare both bind to the acetylcholine receptor; nicotine activates it and curare does not, so one increases firing and the other abolishes it. The word to use is complementary: both molecules have shapes complementary to the binding site, and what differs is whether binding opens the channel.

TRY IT — Reasoning about an unfamiliar poison

A nerve agent inhibits acetylcholinesterase at neuromuscular junctions. Explain why exposure causes continuous muscle contraction, and suggest why it is eventually fatal.

Check your answer

Acetylcholinesterase normally hydrolyses acetylcholine in the cleft. Inhibited, the enzyme cannot break it down, so acetylcholine stays in the cleft and remains bound to the receptors on the postsynaptic membrane.

The receptor sodium channels therefore stay open, sodium keeps entering and the muscle fibre membrane is held depolarised. Action potentials are generated repeatedly, calcium keeps being released inside the fibre and the muscle contracts continuously instead of relaxing between impulses.

It is fatal because the same junctions serve the muscles used in breathing. With the diaphragm and intercostal muscles held contracted, ventilation stops. Antidotes work by blocking the receptors, which prevents acetylcholine binding even though it is still present.

The general move in questions like this is to find the step in the sequence that has been altered and then follow the consequences forward one step at a time. Here the altered step is the last one, and every effect comes from transmitter that should have gone and did not.

In the exam

Check yourself

A postsynaptic neurone receives inputs from three presynaptic neurones. Each excitatory input depolarises it by 6 mV; one inhibitory input hyperpolarises it by 9 mV. The resting potential is −70 mV and threshold is −55 mV. Determine whether an action potential is produced when all three excitatory neurones fire together, and when the inhibitory neurone fires alongside them. Explain what the neurone is doing in each case.

Answer

Threshold requires a depolarisation of 15 mV, from −70 mV to −55 mV. Three excitatory inputs together give 3 × 6 = 18 mV, which takes the membrane to −52 mV. That is past threshold, so voltage-gated sodium channels open and an action potential is produced. This is spatial summation: no single input would have done it, since 6 mV alone reaches only −64 mV.

With the inhibitory input firing as well, the total is 18 − 9 = 9 mV of depolarisation, reaching −61 mV. That is short of threshold, so no action potential is produced.

The inhibitory synapse achieves this by opening chloride or potassium channels, making the inside of the postsynaptic neurone more negative and so raising the excitatory input needed to reach threshold.

Read together, the two cases describe what a postsynaptic neurone is for. It is not a relay that passes on whatever it receives; it adds up positive and negative inputs arriving at that moment and fires only if the total clears a fixed bar. A single neurone in the brain may receive thousands of such inputs, and the decision it makes is this same arithmetic on a larger scale.

Questions

Written to the command words the boards use. Try them on paper before opening a scheme: the marks go to points made, not to length.

Question 15 marks

Describe what happens at a cholinergic synapse from the moment an action potential arrives at the presynaptic knob to the moment the cleft is cleared again.

Mark scheme
  1. B1 the arriving action potential depolarises the membrane of the knob, so voltage-gated calcium channels open and calcium ions diffuse in
  2. B1 the influx of calcium causes vesicles of acetylcholine to move to the presynaptic membrane and fuse with it, releasing their contents by exocytosis
  3. B1 acetylcholine diffuses across the 20 nm cleft down its concentration gradient and binds to receptor sites on the postsynaptic membrane
  4. B1 the receptors are sodium channels, so binding opens them, sodium ions diffuse into the postsynaptic neurone and depolarise it, and a new action potential begins if threshold is reached
  5. A1 acetylcholinesterase in the cleft hydrolyses the acetylcholine, and the products are reabsorbed into the knob and recombined using ATP from its mitochondria

Question 24 marks

Explain how an inhibitory synapse reduces the chance that the postsynaptic neurone produces an action potential, and explain why inhibition is useful rather than a fault in the system.

Mark scheme
  1. B1 the receptors at an inhibitory synapse open chloride channels, letting negative chloride ions in, or potassium channels, letting positive potassium ions out
  2. B1 either movement makes the inside of the postsynaptic membrane more negative, so it is hyperpolarised rather than depolarised
  3. B1 a larger excitatory input is now needed to bring the membrane to the threshold of about −55 mV
  4. A1 this lets a postsynaptic neurone weigh positive against negative inputs, so signals are sharpened, unwanted movements are suppressed and the whole network does not fire at once

Question 34 marks

A toxin from a marine snail prevents the voltage-gated calcium channels in presynaptic knobs from opening. Suggest the effect of this toxin on transmission at a neuromuscular junction, and suggest why an injection of extra acetylcholine into the cleft would not restore normal control of the muscle.

Mark scheme
  1. B1 calcium ions could not diffuse into the synaptic knob when an action potential arrived
  2. B1 without the calcium influx the vesicles would not move to the presynaptic membrane and fuse with it, so no acetylcholine would be released into the cleft
  3. B1 no receptors on the postsynaptic membrane would be occupied, so no sodium channels would open, the muscle fibre membrane would not depolarise and the muscle would be paralysed
  4. A1 injected acetylcholine would bind and depolarise the fibre, but the amount present would no longer depend on the impulses arriving, so the contraction could not be graded or timed by the nervous system

Question 43 marks

Explain why transmission across a synapse can happen in one direction only, and explain why this matters for a reflex arc.

Mark scheme
  1. B1 vesicles of acetylcholine are found only in the presynaptic knob, so the neurotransmitter can only be released on that side
  2. B1 receptors complementary to acetylcholine are found only on the postsynaptic membrane, so it can only be detected on the other side
  3. A1 an impulse arriving at the postsynaptic side would find nothing to release and nothing on the far side to detect it, so a reflex arc runs reliably from receptor to effector and never backwards

Question 53 marks

Compare spatial summation with temporal summation at a postsynaptic neurone.

Mark scheme
  1. B1 spatial summation adds inputs arriving at the same time from several different presynaptic neurones, whereas temporal summation adds impulses arriving in quick succession from a single presynaptic neurone
  2. B1 in spatial summation the depolarisations are produced at different points on the membrane at once, whereas in temporal summation the transmitter from the first impulse has not yet been hydrolysed when the second arrives
  3. B1 both reach threshold by adding small excitatory postsynaptic potentials together, and neither could be reached by one impulse at one synapse acting alone

Question 62 marks

Give the name of the neurotransmitter used at a cholinergic synapse, and give the name of the enzyme that removes it from the synaptic cleft.

Mark scheme
  1. B1 the neurotransmitter is acetylcholine
  2. B1 the enzyme is acetylcholinesterase, which hydrolyses it into choline and ethanoic acid

Worth remembering

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