Crossing the Synaptic Cleft
Neurons do not physically touch. They communicate across the synaptic cleft, a microscopic gap between the presynaptic terminal button and the postsynaptic membrane. When an action potential reaches the terminal button, voltage-gated calcium (Ca2+) channels open, and the resulting Ca2+ influx causes synaptic vesicles — small sacs packed with neurotransmitter — to fuse with the membrane and spill their contents into the cleft.
Released neurotransmitter diffuses across the cleft and binds receptors on the postsynaptic membrane. Two receptor families respond differently: ionotropic receptors are ligand-gated ion channels that open immediately for a brief, fast effect; metabotropic receptors are G-protein-coupled and trigger slower, longer-lasting second-messenger cascades. Binding can produce an EPSP (excitatory postsynaptic potential — depolarizing, e.g. via Na+ influx, moving the neuron toward threshold) or an IPSP (inhibitory postsynaptic potential — hyperpolarizing, e.g. via Cl- influx or K+ efflux, moving it away from threshold).
A single EPSP is rarely enough to reach threshold on its own. Summation solves this: temporal summation adds up EPSPs from one synapse firing repeatedly in quick succession, while spatial summation adds up EPSPs (and subtracts IPSPs) arriving from many synapses at once. The postsynaptic neuron's decision to fire is really a running tally of excitation minus inhibition at the axon hillock.
Once the signal has been passed on, neurotransmitter must be cleared quickly or the postsynaptic cell would stay switched on. Reuptake pumps leftover transmitter back into the presynaptic terminal for recycling, while enzymatic degradation (e.g. acetylcholinesterase breaking down acetylcholine) destroys it in the cleft.
Common pitfall: assuming every synaptic signal is excitatory. Roughly as much synaptic traffic is inhibitory (IPSPs) as excitatory (EPSPs) — cognition depends as much on well-timed inhibition as on excitation.