cotransmission

Cotransmission, or co-release, is the phenomenon in which a single presynaptic neuron releases more than one neurotransmitter at its synapses or release sites. This challenges the older one transmitter per neuron view and helps explain how a single neuron can exert diverse effects on its targets. The transmitters can include classical small-molecule transmitters such as acetylcholine, glutamate, GABA, glycine, norepinephrine, and dopamine, as well as neuropeptides. In many cases, these different transmitters are stored in separate vesicle populations within the same nerve terminal.

Mechanisms and dynamics of release are central to cotransmission. Small clear vesicles typically carry fast-acting transmitters, while dense-core vesicles carry neuropeptides that often produce slower, longer-lasting modulatory effects. These vesicle types can have distinct calcium thresholds and release probabilities, so the pattern and frequency of neuronal activity can preferentially trigger the release of one transmitter over another. Consequently, a given synapse can generate both rapid postsynaptic responses and longer-lasting modulation, depending on the stimulus.

Evidence of cotransmission is widespread across the nervous system, including various central circuits and autonomic pathways. Examples include neurons that release both dopamine and glutamate, noradrenaline with ATP or neuropeptides, or acetylcholine with other modulators in specific circuits. The functional significance lies in flexible signaling: fast synaptic effects coupled with slower modulation, context-dependent synaptic plasticity, and nuanced regulation of network activity.

Ongoing research continues to map where cotransmission occurs and how it shapes behavior, development, and disease.