Receptors with opposing functions are in postsynaptic microdomains under one presynaptic terminal

Fast excitatory synaptic transmission through vertebrate autonomic ganglia is mediated by postsynaptic nicotinic acetylcholine receptors (nAChRs), We demonstrate a unique postsynaptic receptor microheterogeneity on chick para sympathetic ciliary ganglion neurons-under one presynaptic terminal, nAChRs and glycine receptors formed separate but proximal clusters. Terminals wer e loaded with [H-3]glycine via the glycine transporter-1 (GlyT-1), which lo calized to the cholinergic: presynaptic terminal membrane; depolarization e voked [H-3]glycine release that was calcium independent and blocked by the GlyT-1 inhibitor sarcosine. Ganglionic synaptic transmission mediated by nA ChRs was attenuated by glycine. Coexistence of separate clusters of recepto rs with opposing functions under one terminal contradicts Dale's principle and provides a new mechanism for modulating synaptic activity in vivo.