CorpusHuman Anatomy

Chemical Synapse

Axospinous synapse, schematic (not to scale)

A chemical synapse in close-up. The presynaptic axon terminal (bouton) lies above, packed with neurotransmitter-filled synaptic vesicles and a mitochondrion. Below it is the synaptic cleft, and below that the postsynaptic membrane of the receiving dendrite, with its postsynaptic density and ligand-gated receptor channels. An astrocyte process wraps the edge of the cleft (the "tripartite synapse"). The cleft is really only about 20–40 nm wide.

The animation runs as one loop. An action potential arrives and voltage-gated Ca²⁺ channels open at the active zone. A docked vesicle fuses and releases its transmitter, which diffuses across the cleft and binds receptor channels. The channels let Na⁺ in and generate an EPSP. The signal then ends through reuptake, enzymatic breakdown and uptake by the astrocyte, and the vesicle membrane is recycled by endocytosis.

Step-by-step

  1. 1 · Action potential invades the terminal

    An action potential travels down the axon and depolarises the presynaptic bouton. The bouton contains vesicles of transmitter, a readily releasable pool docked at the active zone, and mitochondria that supply the ATP needed for release and recycling.

  2. 2 · Voltage-gated Ca²⁺ channels open

    Depolarisation opens N- and P/Q-type voltage-gated Ca²⁺ channels at the active zone. Ca²⁺ floods in (≈ 1–2 mM outside vs ≈ 0.1 µM inside), producing a brief, very local rise in Ca²⁺ next to docked vesicles. This Ca²⁺ is the essential trigger for transmitter release.

  3. 3 · Vesicle fusion & exocytosis

    Ca²⁺ binds synaptotagmin on docked vesicles. The already-assembled SNARE complex (synaptobrevin + syntaxin + SNAP-25) completes zippering, the vesicle membrane fuses with the presynaptic membrane, and a pore opens. A quantum of transmitter spills into the cleft. Botulinum and tetanus toxins block release at this step by cleaving SNAREs.

  4. 4 · Diffusion across the cleft

    Transmitter molecules diffuse across the ≈ 20–40 nm synaptic cleft in microseconds. Together with Ca²⁺ entry and exocytosis this gives a total synaptic delay of ≈ 0.5 ms. Because the delay occurs at each synapse, a pathway with more synapses responds more slowly.

  5. 5 · Receptor binding → postsynaptic potential

    Transmitter binds ligand-gated ion channels anchored in the postsynaptic density. Cation channels (e.g. AMPA or nicotinic receptors) let Na⁺ in and produce a depolarising EPSP. Cl⁻ channels (GABA-A, glycine) produce an inhibitory IPSP. These graded potentials spread passively along the dendrite and summate toward the axon initial segment.

  6. 6 · Termination of the signal

    Transmitter must be removed quickly. Reuptake transporters return it to the terminal (the target of SSRIs and cocaine). Enzymes destroy it, e.g. acetylcholinesterase splits ACh into choline and acetate, and MAO and COMT break down monoamines. Some transmitter simply diffuses away, and astrocytes take up glutamate through EAAT transporters and convert it to glutamine.

  7. 7 · Vesicle recycling & refilling

    Vesicle membrane added to the terminal surface is taken back by clathrin- and dynamin-dependent endocytosis beside the active zone. The new vesicle is acidified by a V-type H⁺-ATPase, refilled by its vesicular transporter (VAChT, VMAT, VGLUT), and returns to the pool, ready for the next action potential.

Labelled parts

  • Postsynaptic neuron (dendrite / spine)
  • Postsynaptic potential (EPSP / IPSP)
  • Postsynaptic membrane & density
  • Astrocyte
  • Presynaptic terminal (bouton)
  • Action potential
  • Mitochondrion
  • Synaptic vesicles
  • SNARE complex & synaptotagmin
  • Active zone
  • Vesicle recycling (endocytosis)
  • Voltage-gated Ca²⁺ channels
  • Reuptake transporter
  • Degrading enzyme
  • Ligand-gated ion channels (ionotropic receptors)
  • Metabotropic (G-protein-coupled) receptor
  • Neurotransmitters
  • Synaptic cleft