Synapse, Neurotransmitters and Drugs

The chemical synapse

A synapse is the junction between two neurons (or between a neuron and an effector such as a muscle fibre). The two cells do not touch. They are separated by a tiny gap, so an electrical impulse cannot jump across. Instead, the message is carried by a chemical, a neurotransmitter.

A chemical synapse has three parts:

• the presynaptic terminal (the end of the axon sending the signal), which contains vesicles full of neurotransmitter;

• the synaptic cleft, the narrow gap between the cells;

• the postsynaptic membrane (on the next neuron's dendrite or cell body), which carries receptors that fit the neurotransmitter.

The receptors are specific: each fits only its own neurotransmitter, like a lock and key. That is why a drug with a similar shape can sometimes mimic or block a neurotransmitter.

Events at a synapse

The sequence is always the same, so learn it in order.

Because neurotransmitter is released on one side only and receptors are on the other, the impulse can only travel in one direction across a synapse.

The neurotransmitter must not keep acting, or the postsynaptic neuron would fire continuously. It is removed in two main ways:

• Enzymatic breakdown. An enzyme in the cleft destroys it. At neuromuscular junctions the neurotransmitter is acetylcholine, broken down by the enzyme acetylcholinesterase.

• Reuptake. Transporter proteins in the presynaptic membrane take the neurotransmitter back into the terminal, where it can be repackaged into vesicles and reused. Dopamine and serotonin are removed in this way.

Drugs and disorders at the synapse

Almost every drug that affects the nervous system works by interfering with one step of synaptic transmission. There are only a few ways to do it:

Cocaine blocks dopamine reuptake transporters, so dopamine builds up in the cleft and overstimulates the reward pathway. With repeated use the postsynaptic neuron reduces the number of its dopamine receptors. The same dose then has less effect (tolerance) and the person feels unwell without the drug (dependence). In Ireland, support is available through the HSE (for example your GP and addiction services), and organisations such as Narcotics Anonymous and the Ana Liffey Drug Project.

Parkinson's disease is a disorder in which dopamine-producing neurons in the brain degenerate. Dopamine itself cannot be given as a tablet because it does not cross the blood–brain barrier. L-dopa, its precursor, does cross, and is converted to dopamine in the brain. Loss of dopamine at synapses controlling movement causes tremor, muscle rigidity and slow movement. Because neurons keep dying, L-dopa treats the symptoms but does not stop the disease, and it becomes less effective over time.

Dopamine, endorphins and lifestyle

Two neurotransmitters link synapses to everyday choices.

• Dopamine is involved in reward, motivation and pleasure, and in controlling movement. Achieving a goal, such as scoring in a GAA match or finishing a parkrun, increases its release. Dopamine release is also increased by some foods and by drugs of abuse.

• Endorphins are the body's natural painkillers. They bind to receptors in the brain and block pain signals, producing a feeling of wellbeing. Sustained exercise (the "runner's high"), laughing and social activity increase their release.

Opioid drugs such as morphine bind to the same receptors as endorphins and relieve severe pain. With prolonged use, the body reduces its own endorphin production and the number of receptors. When the drug is stopped, there are too few endorphins and receptors to control pain and mood, causing withdrawal symptoms. Opioids are valuable for severe pain but carry a risk of dependence, so they must be prescribed carefully. For mild pain, natural alternatives such as regular exercise, which raises endorphins without these risks, may be sufficient.

Back to the start: the signal in your arm crossed each synapse as a chemical message. Release of neurotransmitter, binding to receptors and inactivation made it fast, one-directional and controllable, and these are exactly the steps drugs and diseases interfere with.

Summary

• A synapse is the junction between neurons: presynaptic terminal (vesicles), synaptic cleft and postsynaptic membrane (receptors).

• Sequence: action potential, Ca²⁺ enters, vesicles release neurotransmitter, it diffuses across the cleft, binds receptors, a new impulse starts. Transmission is one-way.

• Neurotransmitter is inactivated by an enzyme (acetylcholinesterase breaks down acetylcholine) or by reuptake.

• Drugs and disorders act by blocking release, mimicking or blocking receptors, inhibiting breakdown, blocking reuptake or destroying neurons (Parkinson's disease).

• Dopamine (reward, movement) and endorphins (natural pain relief) are influenced by lifestyle choices; prolonged drug use causes tolerance, dependence and withdrawal.