Abstract
Several recent studies including ours have revealed that the activity of the postsynaptic neuron can influence presynaptic function through endogenous cannabinoids (endocannabinoids). In this presentation, we will introduce our recent studies on this phenomenon in the hippocampus. We made paired whole-cell recordings from cultured hippocampal neurons prepared from newborn rats or mice, recorded evoked excitatory and inhibitory postsynaptic currents and examined roles of endocannabinoids in the modulation of synaptic transmission. We have obtained the following results: (1) Endocannabinoids can be released from postsynaptic neurons either by depolarization or by activation of Gq/11-coupled receptors including group I metabotropic glutamate receptors (mGluRs) and M1/M3 muscarinic receptors. (2) Postsynaptic depolarization and activation of group I mGluRs or M1/M3 receptors work in a cooperative manner to release endocannabinoids. (3) The released endocannabinoids act retrogradely on presynaptic cannabinoid CB1 receptors and suppress the transmitter release. (4) Among three candidates of endocannabinoids (2-arachidonyl-glycerol (2-AG), anamdamide, noladine ester), 2-AG is the most effective in suppressing synaptic transmission. These results indicate that endocannabinoids mediate retrograde signals, by which the postsynaptic neuronal activity influences the transmitter release from presynaptic terminals. Wide distributions of CB1 and Gq/11-coupled receptors suggest that similar endocannabinoid-mediated retrograde modulation may function in various brain regions. [Jpn J Physiol 54 Suppl:S33 (2004)]
