MULTIPLE NEUROTRANSMITTER SYNTHESIS, RELEASE, AND SIGNALING FROM INDIVIDUAL NEURONS
Many, perhaps most, nerve terminals co-localize and release multiple neurotransmitters (NT), each presumably packaged in its own synaptic vesicles. Major co-localized NTs, sorted by transmitter and by fiber type, are presented in the table.Some authors have noted as many as seven or more NTs present in a single type of nerve terminal. It should be noted that some NTs are present in the presynaptic cytoplasm and are not released by quantal (vesicle-based) release. Some NTs are packaged in vesicles in the cell body and transported by axonal transport (e.g., neuropeptides), while other NTs are synthesized and/or packaged locally in the nerve terminals (e.g., amino acids, monoamines).
NT release is usually nonlinear, with some NTs diminishing their quantal release at higher action potential (AP) frequencies, while other co-localized NTs (especially some neuropeptides) are released only at much higher AP frequencies. A further phenomenon affecting the functional consequence of NT release is the frequent NT-receptor mismatch. Some NTs are released into a synaptic cleft and immediately activate receptors on the postsynaptic site (e.g., ACh at the neuromuscular junction). However, some NTs, when released, have no local receptors with which to interact, except at distant sites. Hence, NT-receptor activation in these circumstances may occur only during particularly robust or prolonged NT transmitter release.