The Synapse

What a synapse is

A synapse is the specialised point of contact where one neuron passes information to another cell, which may be a second neuron, a muscle fibre, or a gland. It is the working joint of the nervous system. The neuron sending the signal is called the pre-synaptic cell, and the one receiving it is the post-synaptic cell. The two are not simply wired together end to end; they meet at a carefully organised interface built to convert, and often to modify, the message as it passes.

The striking feature of most synapses is that the cells do not actually touch. A microscopic gap, the synaptic cleft, separates the pre-synaptic membrane from the post-synaptic one. This gap is tiny, on the order of tens of nanometres, but it is real, and it changes everything about how the signal crosses. An electrical impulse cannot simply leap across empty space in the way it flows along a continuous membrane. Instead the sending cell converts its electrical signal into a chemical one, releasing molecules that drift across the gap and act on the receiving cell. This is the chemical synapse, and it is by far the most common type in the human brain.

A single neuron may carry thousands of synapses on its dendrites and cell body, each a small inbound channel. The neuron continuously weighs all of these inputs together, and the overall balance of what arrives across its synapses determines whether it will, in turn, fire a signal of its own. Understanding the synapse is therefore the key to understanding how the brain computes: it is where one cell's output becomes another's input.

Chemical transmission step by step

Chemical synaptic transmission is a rapid, tightly ordered sequence. It begins when an impulse arrives at the sending terminal and ends, a fraction of a millisecond later, with a change in the receiving cell. The following steps trace the message across the gap.

1. The impulse arrives

   An action potential travels down the axon and reaches the pre-synaptic terminal, the swollen ending of the sending neuron. Here the brief change in membrane voltage sets the whole process in motion.

2. Calcium channels open

   The arriving voltage opens voltage-gated calcium channels in the terminal membrane. Because calcium is far more concentrated outside the cell than inside, it rushes in through these channels, producing a sharp local rise in calcium just inside the terminal.

3. Vesicles release their transmitter

   That surge of calcium is the trigger. It causes synaptic vesicles, tiny membrane-bound sacs already loaded with neurotransmitter, to fuse with the pre-synaptic membrane and empty their contents into the synaptic cleft. This process, releasing a packet of transmitter, is called exocytosis.

4. Transmitter crosses the cleft

   The released neurotransmitter diffuses across the narrow gap. Because the distance is so small, this crossing takes only a fraction of a millisecond, which is why chemical synapses can still be fast despite the extra chemical step.

5. Receptors bind the transmitter

   On the far side, the transmitter binds to specific receptor proteins embedded in the post-synaptic membrane. Each receptor recognises a particular neurotransmitter, the way a lock accepts one key, so the message is delivered only to cells equipped to read it.

6. Ion channels open and a potential forms

   Binding opens ion channels in the post-synaptic membrane, letting charged ions flow in or out. This shifts the voltage of the receiving cell, producing a post-synaptic potential: excitatory if it pushes the cell toward firing, inhibitory if it pushes it away.

The receiving neuron does not usually fire from a single synapse. Instead it sums many post-synaptic potentials arriving from many synapses at once. If the combined effect is strong enough to reach threshold, the cell generates its own impulse and the chain continues. In this way each synapse casts a small vote, and the neuron tallies them moment by moment.

Clearing the signal

A synapse that could only turn on would be useless. For the message to be crisp, the neurotransmitter must be removed from the cleft quickly once it has acted, so the synapse can reset for the next impulse. There are two main ways this clearance happens, and both are fast.

Clearance is not a footnote: it is central to how the nervous system is tuned, and it is where many medicines act. Drugs that block reuptake leave a transmitter in the cleft for longer, strengthening its effect, which is how a common class of antidepressants that block serotonin reuptake works. Understanding clearance therefore matters both for how the synapse works normally and for how it can be adjusted.

Electrical synapses

Not every synapse uses chemicals. At an electrical synapse the two cells are joined directly by clusters of channels called gap junctions. These channels line up across the membranes of the two cells and form open pores, so that ions and the electrical current they carry can pass straight from one cell into the next with almost no delay.

This direct coupling gives electrical synapses two distinctive properties. First, they are extremely fast: because there is no chemical step, the signal passes essentially instantly, which suits circuits that must act in tight synchrony. Second, they are typically bidirectional, so current can flow either way between the coupled cells, unlike a chemical synapse where the signal runs only from pre-synaptic to post-synaptic side. Electrical synapses are less common in the mammalian brain than chemical ones, and they offer far less scope for modifying the signal, but where speed and synchrony matter most they are invaluable.

Excitatory and inhibitory synapses

A synapse does not only pass a message on; it also decides in which direction to push the receiving cell. Whether a synapse is excitatory or inhibitory depends on the transmitter released and the receptor it meets, and this distinction is fundamental to how the brain balances its activity.

Healthy brain function depends on a careful balance between these two forces. Too little inhibition and activity can spread unchecked, as in the runaway firing of a seizure; too much and signalling is damped down. Because each neuron sums excitatory and inhibitory inputs continuously, the synapse is not just a relay but a genuine site of computation, weighing evidence for and against firing before the cell commits.

Synaptic plasticity and learning

The most remarkable property of the synapse is that it does not stay fixed. Its strength, how much effect the pre-synaptic cell has on the post-synaptic one, can change with use. This capacity for lasting change is called synaptic plasticity, and it is widely held to be the physical basis of learning and memory. When we learn, we are, at the cellular level, adjusting the strengths of synapses.

A useful way to summarise the underlying rule is that neurons which fire together tend to wire together: when the activity of one cell reliably helps drive another, the synapse between them is reinforced. Together, potentiation and depression give the brain a way to record experience directly in the strength of its connections, refining its own wiring with every new thing it learns.

Chemical versus electrical synapses

The two kinds of synapse solve the same problem, passing a signal between cells, in very different ways. The contrast below sets out where each excels.

The trade-off is clear. Electrical synapses win on raw speed and are ideal where cells must act as one, but they offer little room to shape or store a signal. Chemical synapses pay a small price in speed for an enormous gain in flexibility, and it is that flexibility, above all the ability to change their strength, that makes them the dominant currency of thought.

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