Synaptic Transmission: Step-by-Step Neurotransmission Across the Synaptic Cleft

Chemical synapses transmit signals via neurotransmitter release, diffusion, and receptor binding.

Sequence

1. Action potential arrival at presynaptic terminal → depolarization.
2. Voltage-gated Ca²⁺ channels open → Ca²⁺ influx (trigger).
3. Vesicle fusion (SNARE complex): Synaptotagmin senses Ca²⁺ → vesicles dock/fuse → exocytosis of neurotransmitter.
4. Diffusion across cleft (20–40 nm) → binding to postsynaptic receptors.
5. Receptor activation:
   • Ionotropic (LGIC): Direct ion channel opening (AMPA/NMDA → Na⁺/Ca²⁺ = EPSP; GABAₐ/glycine → Cl⁻ = IPSP).
   • Metabotropic (GPCR): G-protein → second messengers → slow modulation.
6. Postsynaptic potential summation: Spatial + temporal integration of EPSPs/IPSPs at axon initial segment.
7. Threshold reached? → AP generated (output) or not (inhibition).
8. Termination: Reuptake (SERT, DAT, NET, GAT), enzymatic degradation (AChE, MAO, COMT), diffusion.

Key Concepts

• Quantal release (miniature EPSPs).
• Short-term plasticity (facilitation, depression).
• Long-term plasticity (LTP/LTD) → learning.
• Dale's principle: Neuron releases same NT at all terminals (mostly true).

Synaptic precision underlies all neural computation.