CorpusHuman Anatomy
NervousCell process

Synapse

Synapsis

Also known as: chemical synapse, electrical synapse, gap junction, synaptic transmission, EPSP, IPSP

The specialised junction where a neuron transmits a signal to another neuron or to an effector cell. Most synapses are chemical, using neurotransmitter released into a 20–40 nm cleft. A minority are electrical, using gap junctions.

Chemical Synapse

Overview

Chemical cleft width≈20–40 nm
Gap-junction gap≈2–4 nm
Synaptic delay (chemical)≈0.5 ms
Synapses in the brain≈10¹⁴–10¹⁵

At a chemical synapse, the presynaptic terminal contains synaptic vesicles (≈40–50 nm, each holding thousands of transmitter molecules, which form a "quantum"), mitochondria, and active zones studded with voltage-gated Ca²⁺ channels (N- and P/Q-type). An arriving action potential opens these channels. Ca²⁺ influx is sensed by synaptotagmin, which triggers SNARE-mediated fusion: synaptobrevin/VAMP on the vesicle zips together with syntaxin and SNAP-25 on the membrane, and the vesicles undergo exocytosis. Transmitter diffuses across the synaptic cleft (≈20–40 nm) and binds receptors in the postsynaptic density.

Ionotropic (ligand-gated channel) receptors, such as nicotinic ACh, AMPA, NMDA, GABA-A and glycine receptors, produce fast (milliseconds) responses. Metabotropic (G-protein-coupled) receptors, such as muscarinic, adrenergic, dopamine, GABA-B and mGluR receptors, produce slower, longer-lasting and modulatory effects through second messengers. The total synaptic delay is ≈0.5 ms. Transmission is one-way, can be excitatory or inhibitory, and is modifiable (plastic).

An excitatory postsynaptic potential (EPSP) is a graded depolarisation, usually from Na⁺ influx. An inhibitory postsynaptic potential (IPSP) is a hyperpolarisation or shunting response from Cl⁻ influx (GABA-A, glycine) or K⁺ efflux (GABA-B). A single EPSP (≈0.5–1 mV at a central synapse) is far below threshold. The neuron fires only when inputs summate at the axon hillock: temporal summation from repeated input at one synapse, and spatial summation from simultaneous input at many synapses. Signalling ends through reuptake by transporters (glutamate, GABA, noradrenaline, dopamine, serotonin), enzymatic breakdown (acetylcholinesterase; MAO and COMT for catecholamines) and diffusion. Vesicles are recycled by clathrin-mediated endocytosis.

Electrical synapses are gap junctions, made of connexons of six connexins (connexin 36 in neurons), that connect the cytoplasm of two cells across a ≈2–4 nm gap. They pass current directly in both directions with virtually no delay, synchronising groups of neurons in the inferior olive, retina, hypothalamus and some interneuron networks. They are also the main coupling in cardiac and visceral smooth muscle.

Parts & subdivisions

  1. Presynaptic terminal
    The bouton, containing synaptic vesicles, mitochondria, active zones with voltage-gated Ca²⁺ channels, and the SNARE and synaptotagmin machinery.
  2. Synaptic cleft
    An extracellular gap of ≈20–40 nm, containing adhesion molecules (neurexin–neuroligin) and, at cholinergic synapses, acetylcholinesterase.
  3. Postsynaptic membrane and density
    Receptors anchored by scaffolding proteins (PSD-95 at glutamatergic synapses, gephyrin at inhibitory synapses), plus signalling enzymes.
  4. Axodendritic synapses
    The most common type. Excitatory synapses often lie on dendritic spines and are asymmetric (Gray type I), with round vesicles.
  5. Axosomatic synapses
    Often inhibitory, symmetric (Gray type II) with flattened vesicles, for example basket-cell synapses on pyramidal cells. Located close to the trigger zone, so they control output powerfully.
  6. Axoaxonic synapses
    Terminals on another axon's initial segment (chandelier cells) or terminal. They mediate presynaptic inhibition or facilitation, for example in the dorsal horn.
  7. Electrical synapse (gap junction)
    Connexon channels with a ≈2–4 nm gap. Bidirectional, essentially no delay, used for synchrony.

Function

  • Transmit signals between neurons and from neurons to muscle and gland cells.
  • Integrate excitatory and inhibitory input (summation) to determine neuronal output.
  • Amplify, filter and modulate signals (neuromodulation).
  • Store information through long-term potentiation and depression (learning and memory).
Physiology

Long-term potentiation (LTP), best studied at hippocampal CA1, works as follows. Strong depolarisation expels the Mg²⁺ block from NMDA receptors, allowing Ca²⁺ entry. Ca²⁺ activates CaMKII, which inserts extra AMPA receptors, strengthening the synapse. Long-term depression (LTD) follows modest Ca²⁺ entry and removes AMPA receptors. Short-term plasticity includes paired-pulse facilitation (residual Ca²⁺) and depression (vesicle depletion).

Clinical significance

Botulinum versus tetanus toxin

Both are zinc proteases that cleave SNARE proteins. Botulinum toxin (Clostridium botulinum) acts at peripheral cholinergic terminals. It cleaves SNAP-25, syntaxin or synaptobrevin, blocking ACh release and causing descending flaccid paralysis with dilated pupils. It is used therapeutically for dystonia, spasticity and cosmetic purposes. Tetanus toxin (C. tetani) travels retrogradely to the spinal cord. There it cleaves synaptobrevin in inhibitory interneurons (Renshaw cells), blocking glycine and GABA release and causing spastic paralysis: trismus (lockjaw), risus sardonicus, opisthotonus.

Lambert–Eaton myasthenic syndrome

Autoantibodies against presynaptic P/Q-type voltage-gated Ca²⁺ channels reduce ACh release. It is often paraneoplastic (small-cell lung cancer). It presents with proximal weakness that improves with repeated effort (facilitation), hyporeflexia and autonomic features (dry mouth). Contrast myasthenia gravis, which is caused by antibodies to postsynaptic AChRs and shows fatigability.

Drugs acting at synapses

Organophosphates and nerve agents irreversibly inhibit acetylcholinesterase, causing cholinergic crisis (SLUDGE/DUMBELS, bradycardia, miosis, bronchorrhoea, fasciculations then paralysis); treat with atropine and pralidoxime. SSRIs block serotonin reuptake. Cocaine blocks the dopamine, noradrenaline and serotonin transporters. Amphetamines reverse those transporters. Strychnine blocks glycine receptors.

Compiled from standard anatomy and physiology references — see the Nervous System sources. For education only; not medical advice.