Neurotransmitters

Neurotransmitters are chemical messengers that transmit signals across synapses from a presynaptic neuron to a postsynaptic cell, including other neurons, muscle, or gland cells. They are released in response to an action potential and bind to specific receptors on the postsynaptic membrane, producing excitatory or inhibitory effects that influence neural circuits and behavior.

They are broadly categorized into small-molecule transmitters and neuropeptides. Small-molecule transmitters include acetylcholine; amino acids such as glutamate (excitatory) and GABA and glycine (inhibitory); and biogenic amines such as dopamine, norepinephrine, serotonin, and histamine. Neuropeptides, such as substance P and endorphins, are synthesized as larger precursors and released from dense-core vesicles, often modulating network activity rather than providing direct transmission.

Release and receptors: neurotransmitters are stored in synaptic vesicles and released upon Ca2+ influx. They act on ionotropic receptors (ligand-gated ion channels) or metabotropic receptors (G-protein-coupled receptors), which can directly alter ionic conductance or initiate second messenger cascades that regulate excitability and signaling.

Terminations/recycling: action is terminated by reuptake into the presynaptic neuron or neighboring glia, or by enzymatic degradation. Examples include acetylcholine breakdown by acetylcholinesterase; monoamines degraded by monoamine oxidase (MAO) and catechol-O-methyltransferase (COMT); and transporter-mediated reuptake for serotonin, dopamine, and norepinephrine.

Roles and clinical relevance: glutamate is the primary excitatory transmitter in the CNS; GABA is the main inhibitory transmitter. Acetylcholine governs motor function and some cognitive processes; dopamine, norepinephrine, and serotonin modulate mood, motivation, and arousal. Dysregulation is linked to Parkinson’s disease, epilepsy, depression, anxiety, and schizophrenia. Many drugs target these systems to treat such conditions.

Some neurons co-release multiple transmitters, and synaptic signaling is further modulated by neuromodulators and endocannabinoids that can alter release probability or receptor responsiveness.