Inside the Synapse: Vesicles, Receptors and EPSP/IPSP

From electrical spike to chemical message

A neuron communicates with the next cell across a synapse — a narrow gap, the synaptic cleft, roughly 20 nanometres wide, that electrical current cannot cross directly. When an action potential — the brief, all-or-nothing voltage spike that propagates down an axon — reaches the axon terminal, it depolarises the terminal membrane and opens voltage-gated calcium channels. The resulting influx of Ca²⁺ is the trigger that converts an electrical signal into a chemical one.

That calcium influx causes synaptic vesicles — small membrane-bound sacs pre-loaded with neurotransmitter and docked at the presynaptic membrane — to fuse with the membrane and empty their contents into the cleft by exocytosis, all within roughly half a millisecond of the calcium trigger. The neurotransmitter then diffuses the short distance across the cleft and binds to receptor proteins studding the postsynaptic membrane, which is where the message becomes electrical again.

Two receptor mechanisms, two timescales

Ionotropic receptors are themselves ligand-gated ion channels: neurotransmitter binding directly opens the channel, producing a fast postsynaptic current within roughly a millisecond and lasting a few to tens of milliseconds — this is the pathway for fast, moment-to-moment signalling like most excitatory glutamate (AMPA receptor) and inhibitory GABA (GABA-A receptor) transmission. Metabotropic receptors don't form a channel themselves; binding instead activates a G-protein-coupled intracellular signalling cascade that can open separate ion channels indirectly, or alter cell metabolism, over a much slower timescale of hundreds of milliseconds to seconds or longer — this pathway underlies neuromodulation, mood-relevant signalling, and longer-lasting changes in cell excitability rather than moment-to-moment information transfer.

EPSP and IPSP: pushing toward or away from threshold

Whether a given synapse's effect is excitatory or inhibitory depends on which ion channel opens, not on the neurotransmitter itself in any absolute sense — the same neurotransmitter can in principle produce different effects at different receptor types. An excitatory postsynaptic potential (EPSP) opens channels (typically for Na⁺ and/or Ca²⁺) that let positive charge flow into the postsynaptic cell, depolarising it — nudging its membrane potential up, toward the threshold needed to fire its own action potential. An inhibitory postsynaptic potential (IPSP) opens channels (typically for Cl⁻ or K⁺) that hyperpolarise or stabilise the membrane, pushing it away from threshold and making the cell harder to fire.

EPSP:  neurotransmitter → Na+/Ca2+ channels open → depolarisation  → closer to threshold
IPSP:  neurotransmitter → Cl-/K+ channels open   → hyperpolarisation → further from threshold
neuron fires only if:  Σ(EPSPs) - Σ(IPSPs), summed over space & time, exceeds threshold

No single synapse normally fires its target cell on its own — a typical neuron integrates thousands of simultaneous synaptic inputs across its dendrites, and firing depends on summation: EPSPs and IPSPs arriving close together in time (temporal summation) or at nearby locations on the dendritic tree (spatial summation) add together, and the cell fires an action potential only if their net sum, measured at the axon's trigger zone, crosses the firing threshold. A single strong IPSP arriving at the right moment can veto multiple simultaneous EPSPs, which is exactly how inhibitory circuits shape and gate information flow in real neural networks.

Clearing the signal: why synapses don't just stay 'on'

For the synapse to be useful for fast, repeated signalling, the neurotransmitter must be removed from the cleft quickly after release — otherwise receptors would stay activated and the postsynaptic cell would be unable to detect the next, distinct signal. Clearance happens through reuptake (transporter proteins on the presynaptic terminal or nearby glial cells pump neurotransmitter back out of the cleft — the mechanism SSRIs interfere with for serotonin), enzymatic degradation (acetylcholinesterase breaking down acetylcholine in the neuromuscular junction is the classic example), and simple diffusion away from the cleft. Which mechanism dominates and how fast it acts sets the effective duration of that synapse's signal — a design choice as functionally important as the receptor type itself.

Frequently asked questions

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Everything above runs in your browser — open Synapse — Neurotransmitter & EPSP/IPSP and change the parameters while it is running. Nothing is installed, nothing is uploaded, the whole model lives in one tab.