Endogenous cannabinoid as a retrograde messenger from depolarized postsynaptic neurons to presynaptic terminals

Cannabinoid receptors are the molecular targets for the active component De lta (9)-tetrahydrocannabinol of marijuana and hashish, and constitute a maj or family of G protein-coupled seven-transmembrane-domain receptors. They c onsist of type 1 (CBI) and type 2 (CB2) receptors of which the CB1 is rich in various regions of the CNS. Accumulated evidence suggests that endogenou s cannabinoids function as diffusible and short-lived intercellular messeng ers that modulate synaptic transmission. Recent studies have provided stron g experimental evidence that endogenous cannabinoids mediate signals retrog radely from depolarized postsynaptic neurons to presynaptic terminals to su ppress subsequent neurotransmitter release, driving the synapse into an alt ered state. In hippocampal neurons, depolarization of postsynaptic neurons and resultant elevation of [Ca2+](i) lead to transient suppression of inhib itory transmitter release (depolarization-induced suppression of inhibition , DSI). In cerebellar Purkinje cells. on the other hand, depolarization-ind uced elevation of [Ca2+](i) causes transient suppression of excitatory tran smitter release (depolarization-induced suppression of excitation. DSE). DS I and DSE appear to share the same properties and may be a general and impo rtant mechanism by which the postsynaptic neuronal activity can influence t he amount of transmitter release. (C) 2001 Elsevier Science Ireland Ltd and the Japan Neuroscience Society. All rights reserved.