Synapse — Electrical vs Chemical Synapses, Synaptic Properties, EPSP/IPSP and Neurotransmitters

The human brain has roughly 86 billion neurons, and they communicate at synapses. Each synapse has a presynaptic terminal (the end of an axon, where the action potential is turned into transmitter release) and a postsynaptic membrane packed with receptors. The gap between them — the synaptic cleft — is less than 50 nm wide, and transmitter crosses it by diffusion.

Synapses are also named by which part of the second neuron they contact. StatPearls notes that axodendritic synapses tend to be excitatory, axosomatic synapses tend to be inhibitory, and axoaxonic synapses are regulatory: one axon terminal changes how much transmitter another terminal releases (the anatomical basis of presynaptic inhibition and facilitation).

In an electrical synapse the two membranes come extremely close and are linked by gap junctions — paired channels made of connexin subunits (a hexamer called a connexon on each side). Ionic current flows passively from one cell to the next, so transmission is almost instantaneous. The pores are wide enough to let small metabolites such as ATP and second messengers pass as well.

In a chemical synapse the action potential opens presynaptic voltage-gated Ca²⁺ channels, vesicles fuse and release transmitter, and the transmitter must diffuse across the cleft before it can act. That diffusion and the release machinery create the synaptic delay.

1. Synthesis and storage — small-molecule transmitters travel in small clear vesicles; neuropeptides are made on rough ER/Golgi in the cell body and carried in large dense-core vesicles by kinesin along microtubules.
2. Release — the action potential depolarises the terminal, voltage-gated Ca²⁺ channels open and Ca²⁺ rushes in. Ca²⁺ triggers the SNARE complex (syntaxin-1, SNAP-25 and synaptobrevin-2) to fuse vesicles with the membrane at active zones.
3. Receptor activation — the transmitter binds either a ligand-gated ion channel (ionotropic; response in a few milliseconds) or a G-protein-coupled receptor (metabotropic; second messengers such as cAMP, IP₃ and DAG; effects last seconds to minutes).
4. Termination — by reuptake (presynaptic or glial; only small-molecule transmitters can be taken back), enzymatic breakdown (MAO, COMT) or simple diffusion away from the cleft.

Glutamate is handled by a glial cycle: released glutamate is taken up by astrocytes, converted to glutamine, returned to the neuron and recycled. Neuropeptides cannot be taken back up and must be degraded.

Classic physiology textbooks list a set of 'properties of synapses'. Almost all of them follow from the chemical mechanism above.

At the neuromuscular junction, repeated stimulation first facilitates the end-plate potential; as vesicles run out, depression dominates; after the train ends, the next impulse gives an enlarged response (post-tetanic potentiation). These short-term changes occur at virtually all chemical synapses, so synaptic strength constantly depends on recent activity.

A postsynaptic potential (PSP) is excitatory (EPSP) if it makes a postsynaptic action potential more likely and inhibitory (IPSP) if it makes one less likely. What decides this is not the transmitter's name but the reversal potential of the current compared with the threshold.

In the textbook example the neuron rests at about −60 mV with a threshold of −40 mV. Opening Cl⁻ channels when E_Cl is −70 mV produces a hyperpolarising IPSP. Even if E_Cl were −50 mV, the IPSP would be slightly depolarising but still inhibitory, because it clamps the membrane below threshold.

Most central synapses produce PSPs far below threshold, so a neuron fires only when many inputs add together. PSPs sum in space and in time (Purves et al.).

• Spatial summation — PSPs from different synapses active at about the same time add together (E1 + E2 may reach threshold when neither does alone).
• Temporal summation — PSPs from repeated firing of the same input arrive before the previous one has decayed and build on it.
• Algebraic summation — an IPSP subtracts from EPSPs: E1 + I is smaller than E1, and E1 + I + E2 may stay below threshold.

The result is a continuous 'tug-of-war' between excitation and inhibition. If the summed potential at the trigger zone crosses threshold, the neuron fires; if inhibition prevails, it stays silent. This is how a single neuron integrates thousands of inputs.

Monoamines are degraded by MAO (MAO-A: serotonin, melatonin, noradrenaline, adrenaline; both forms: dopamine and tyramine) and catecholamines also by COMT — both are frequent drug targets. For the autonomic receptor pharmacology built on these transmitters, see adrenergic drugs and receptors.

The postsynaptic potential changes described here sit on top of the resting membrane potential; review the Nernst and Goldman equations there to understand why Cl⁻ and cation currents push the membrane in opposite directions.