Synaptic Transmission
Synaptic Transmission
Neurons do not make direct electrical contact with each other — they communicate across tiny gaps called synapses. At a synapse, the electrical signal of an action potential is converted into a chemical signal: a neurotransmitter is released into the gap and binds to receptors on the next cell, converting the chemical signal back into an electrical one. This chemical signalling system allows enormous flexibility, as the effects can be excitatory or inhibitory and can be modulated by a wide range of drugs and other chemicals.
Structure of a Synapse
A synapse consists of three components:
- Pre-synaptic terminal (synaptic knob): the enlarged end of the axon that contains synaptic vesicles — membrane-bound sacs filled with neurotransmitter molecules. Mitochondria are abundant here to supply the energy needed for neurotransmitter synthesis and release.
- Synaptic cleft: an approximately 20–40 nanometre gap between the pre- and post-synaptic membranes, filled with extracellular fluid through which neurotransmitters diffuse.
- Post-synaptic membrane: the membrane of the receiving cell (another neuron, muscle, or gland), embedded with specialised receptor proteins that are complementary in shape to specific neurotransmitters — a lock-and-key arrangement.
The Process of Synaptic Transmission
When an action potential reaches the pre-synaptic terminal, it triggers a sequence of events:
- The action potential causes voltage-gated calcium ion (Ca²⁺) channels to open in the pre-synaptic membrane, allowing calcium to flow in.
- The influx of calcium triggers synaptic vesicles to fuse with the pre-synaptic membrane through a process called exocytosis, releasing their neurotransmitter molecules into the synaptic cleft.
- Neurotransmitters diffuse across the cleft and bind to complementary receptor proteins on the post-synaptic membrane.
- Binding alters the post-synaptic membrane potential, producing either an excitatory post-synaptic potential (EPSP) — making the post-synaptic neuron more likely to fire — or an inhibitory post-synaptic potential (IPSP) — making it less likely to fire.
- Neurotransmitter action is terminated by: reuptake (the pre-synaptic terminal reabsorbs the neurotransmitter for reuse); enzymatic degradation (enzymes in the cleft break down the neurotransmitter); or diffusion away from the cleft.
Excitatory and Inhibitory Neurotransmitters
Neurotransmitters are classified by their effects on the post-synaptic cell. Excitatory neurotransmitters depolarise the post-synaptic membrane (produce EPSPs), making the cell more likely to fire. Inhibitory neurotransmitters hyperpolarise the post-synaptic membrane (produce IPSPs), making it less likely to fire. A neuron typically receives thousands of excitatory and inhibitory inputs simultaneously — the net effect at the axon hillock depends on the balance of EPSPs and IPSPs, a process called summation.
Key Neurotransmitters
| Neurotransmitter | Primary effect | Role / associations |
|---|---|---|
| Acetylcholine (ACh) | Excitatory (at NMJ); variable in CNS | Muscle contraction; attention and memory (Alzheimer's involves ACh deficit) |
| Dopamine | Generally excitatory | Reward, motivation, movement; excess linked to schizophrenia; deficit linked to Parkinson's |
| Serotonin | Generally inhibitory/modulatory | Mood, sleep, appetite; deficit associated with depression and OCD |
| Noradrenaline | Excitatory | Arousal, attention, fight-or-flight; dysregulation linked to depression and anxiety |
| GABA | Inhibitory | Primary inhibitory NT of the CNS; reduces neural excitability; benzodiazepines enhance GABA activity |
Drugs and Synaptic Transmission
Psychoactive drugs and psychiatric medications exert their effects by modifying synaptic transmission. Agonists mimic or enhance neurotransmitter action (e.g. SSRIs increase serotonin availability by blocking reuptake). Antagonists block neurotransmitter action (e.g. antipsychotic drugs block dopamine receptors). Understanding synaptic transmission therefore directly underpins pharmacological treatment of mental disorders.
Key Takeaways
- A synapse consists of the pre-synaptic terminal, synaptic cleft (~20–40 nm), and post-synaptic membrane with receptor proteins.
- Synaptic transmission: action potential → Ca²⁺ influx → vesicle exocytosis → neurotransmitter release → diffusion → receptor binding → EPSP or IPSP.
- Neurotransmitter action is terminated by reuptake, enzymatic degradation, or diffusion.
- Excitatory neurotransmitters produce EPSPs (increase firing probability); inhibitory neurotransmitters produce IPSPs (decrease firing probability); summation at the axon hillock determines whether a post-synaptic action potential fires.
- Key neurotransmitters: ACh (muscle/memory), dopamine (reward/schizophrenia/Parkinson's), serotonin (mood/depression), noradrenaline (arousal), GABA (inhibition/anxiety).
- Drugs modify synaptic transmission as agonists (enhance NT action) or antagonists (block NT action) — the mechanism of many psychiatric medications.