Words to know
synapse
The junction between a neuron and another cell (neuron, muscle or gland) where a signal is passed on.
synaptic cleft
The tiny gap (about 20 nm) between the presynaptic and postsynaptic membranes.
neurotransmitter
A chemical released from a presynaptic terminal that crosses the cleft and binds receptors on the postsynaptic cell.
acetylcholine (ACh)
The neurotransmitter at neuromuscular junctions and in many other synapses.
acetylcholinesterase
An enzyme in the synaptic cleft that breaks down acetylcholine into acetate and choline.
EPSP / IPSP
Excitatory / inhibitory postsynaptic potential: a small depolarization that makes firing more likely / a hyperpolarization that makes it less likely.
summation
Adding together postsynaptic potentials, either from one synapse firing rapidly (temporal) or from many synapses at once (spatial).
reuptake
Transport of a neurotransmitter back into the presynaptic terminal, ending its effect.
A gap in the wire
Neurons don't touch each other. Between the end of one axon and the next cell there is a gap about 20 nanometres wide, thousands of times thinner than a human hair. The action potential can't jump this gap electrically. Instead, the signal is converted into chemicals, which drift across and are turned back into an electrical signal on the other side.
This might sound inefficient, but synapses are where the nervous system does its thinking. At synapses, signals can be strengthened, weakened, added up or blocked. They are also where most drugs and many toxins act.
Acetylcholine and the neuromuscular junction
Every time you move a skeletal muscle, motor neurons release acetylcholine (ACh) at neuromuscular junctions. ACh binds receptors on the muscle fibre that open channels letting Na⁺ in. This depolarizes the muscle membrane and triggers contraction.
The enzyme acetylcholinesterase, sitting in the cleft, breaks ACh down into acetate and choline within milliseconds. The choline is taken back into the terminal and recycled to make new ACh. Without this enzyme, ACh would keep stimulating the muscle, which would contract uncontrollably and then stop responding.
Excitatory and inhibitory synapses
Not every synapse says "fire!". At an excitatory synapse, the neurotransmitter opens channels that let Na⁺ in, producing a small depolarization called an excitatory postsynaptic potential (EPSP). At an inhibitory synapse, the neurotransmitter opens channels that let Cl⁻ in or K⁺ out, making the inside more negative: an inhibitory postsynaptic potential (IPSP).
A single EPSP is usually only a few millivolts, far too small to reach threshold. A typical neuron in the brain receives input from thousands of synapses. At the axon hillock (where the axon leaves the cell body), all the EPSPs and IPSPs are added together:
- Temporal summation: one synapse fires several times in quick succession, and the EPSPs pile up before each one fades.
- Spatial summation: many synapses fire at the same time, and their EPSPs add together.
If the total reaches threshold, the neuron fires an action potential. This is how a neuron "decides": it weighs its excitatory and inhibitory inputs.
Synapses, disorders and medicines
- Parkinson's disease: neurons that release dopamine in a movement-control area of the brain gradually die, causing tremor, stiffness and slow movement. L-dopa, a molecule the brain converts into dopamine, relieves symptoms. (Dopamine itself can't cross from the blood into the brain.)
- Myasthenia gravis: the immune system makes antibodies that block or destroy ACh receptors at neuromuscular junctions, causing muscle weakness. Cholinesterase-inhibitor medicines help by letting ACh last longer.
- Depression and anxiety involve many factors, including how certain neurotransmitter systems work. Some medicines, such as SSRIs (selective serotonin reuptake inhibitors), slow the reuptake of serotonin so it stays in the cleft longer. These are prescribed and monitored by doctors.
- Botulinum toxin, made by a bacterium, blocks the release of ACh, causing paralysis. In tiny, carefully controlled doses (Botox), doctors use it to treat muscle spasms and chronic migraines.
In the lesson on chemical substances, you will see how caffeine, nicotine, alcohol, cannabis and opioids also act at synapses.
Hands-on activityAct out a synapse
You need: 2 or more people, about 15 soft objects (rolled-up socks or crumpled paper balls) as neurotransmitter, 3 bowls or small boxes as receptors, a strip of tape on the floor as the synaptic cleft, and a timer.
- Presynaptic neuron: one person stands on one side of the tape holding the socks (vesicles). Postsynaptic neuron: another person sits on the other side with the 3 bowls in front of them.
- A third person (or the timer) says "action potential!" The presynaptic person tosses 5 socks across the cleft. Each sock that lands in a bowl is a bound receptor.
- Rule: the postsynaptic person can only "fire" (stand up and clap) if at least 2 bowls have socks at the same time (threshold).
- Clean-up enzyme: after 5 seconds, the postsynaptic person must empty the bowls (acetylcholinesterase) or toss socks back (reuptake).
- Try variations: (a) send only 2 socks per "action potential" (a weak signal) and repeat quickly (temporal summation); (b) remove the clean-up rule (an enzyme inhibitor); (c) put a lid on one bowl (a receptor blocker).
Analyse: For each variation, explain what it models and what happened to the postsynaptic "neuron". Then name one way the model is unrealistic. (Real neurotransmitter molecules diffuse randomly in microseconds; real synapses release thousands of molecules from each vesicle.)
What to look for: with no clean-up, the postsynaptic person stays "firing", like overstimulation by an acetylcholinesterase inhibitor; with a lidded bowl, firing is harder, like a receptor-blocking drug; quick repeated weak signals can still reach threshold, like temporal summation.