- Chemical synapse
- The specialised junction between two neurons (or a neuron and its target cell) at which communication occurs through the release and reception of chemical neurotransmitters. The presynaptic terminal contains vesicles packed with neurotransmitter; when an action potential arrives and opens voltage-gated calcium channels, the vesicles fuse with the membrane and release their contents into the synaptic cleft — a gap of approximately 20 nanometres. The transmitter diffuses across and binds to receptors on the postsynaptic membrane, altering its excitability.
- Excitatory and inhibitory transmission
- Neurotransmitters do not carry information as such — they alter the probability that the postsynaptic neuron will fire. Excitatory transmitters (primarily glutamate) depolarise the postsynaptic membrane, bringing it closer to the action potential threshold. Inhibitory transmitters (primarily GABA) hyperpolarise it, pushing it further from threshold. A postsynaptic neuron integrates thousands of excitatory and inhibitory inputs simultaneously; whether it fires depends on the net sum of these inputs — a process of spatial and temporal summation.
- Reuptake
- The primary mechanism by which neurotransmitter action is terminated for monoamine systems: transporter proteins embedded in the presynaptic membrane actively pump the neurotransmitter back into the terminal, where it can be repackaged for re-release. Julius Axelrod's demonstration that norepinephrine is cleared primarily by reuptake rather than enzymatic degradation revealed transporters as drug targets. Drugs that block reuptake — including SSRIs (serotonin), SNRIs (serotonin and norepinephrine), and amphetamines (dopamine and norepinephrine) — increase the concentration of transmitter in the synaptic cleft, prolonging and amplifying postsynaptic effects.
- Ionotropic receptors
- Receptors that are themselves ion channels: binding of a neurotransmitter directly opens the channel, allowing ions to flow across the membrane within milliseconds. Examples include AMPA receptors (sodium/potassium, excitatory), NMDA receptors (calcium, excitatory — also require depolarisation and glycine as a co-agonist), and GABA-A receptors (chloride, inhibitory). Benzodiazepines enhance GABA-A function by increasing the frequency of chloride channel opening without binding to the GABA site itself.
- Metabotropic receptors
- G-protein-coupled receptors (GPCRs) that do not directly control ion channels; instead, binding of a neurotransmitter activates an intracellular G-protein, which triggers a cascade of second-messenger signalling (cAMP, inositol phosphate pathways) that modulates ion channels and gene expression indirectly. The response is slower (seconds to minutes) and more prolonged than ionotropic signalling. All dopamine receptors, most serotonin receptors, and muscarinic acetylcholine receptors are metabotropic. The majority of psychotropic drugs act on this class of receptor.
- Neuromodulation
- A mode of neurotransmitter action in which a chemical messenger alters the gain or responsiveness of neurons without directly driving them to fire or preventing them from doing so. Neuromodulators — dopamine, serotonin, norepinephrine, acetylcholine — are released from diffuse projection systems and bias the activity of large neuronal populations, effectively tuning the signal-to-noise ratio of information processing. Disruption of neuromodulatory systems underlies most major psychiatric disorders: deficient dopamine modulation in the prefrontal cortex is implicated in the cognitive symptoms of schizophrenia; reduced serotonin tone in the monoamine hypothesis of depression; locus coeruleus norepinephrine hyperactivity in PTSD.