Physiological roles of plasticity of inhibitory synaptic transmission

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1. Recent studies have revealed that the activity of postsynaptic neurons can influence presynaptic functions via endocannabinoids that are released from postsynaptic neurons and act retrogradely on presynaptic terminals. In this study, we attempted to clarify physiological roles of endocannabinoid-mediated retrograde modulation of synaptic transmissions.2. We made paired whole-cell recordings from cultured hippocampal neurons prepared from newborn rats, and recorded evoked excitatory and inhibitory postsynaptic currents. Our results are summarized as follows. (1) Endocannabinoids can be released from postsynaptic neurons by depolarization or by activation of group I metabotropic glutamate receptors (mGluR) (Ohno-Shosaku et al., Eur J Neurosci 15, 2002). (2) Endocannabinoid release is also induced by activation of the M_1 and M_3 subtypes of muscarinic acetylcholine receptors (in preparation), (3) Postsynaptic depolarization and activation of group I mGluRs or M_1/M_3 receptors work in a cooperative manner to release endocannabinoids (Ohno-Shosaku et al., Eur J Neurosci, in press). (4) The released endocannabinoids act retrogradely onto presynaptic cannabinoid CB1 receptors and suppress the transmitter release from presynaptic terminals. (5) The cannabinoid-sensitivity of presynaptic terminals is high in a subpopulation (about 50 %) of inhibitory synapses, low in excitatory synapses, and almost absent in the rest of inhibitory synapses (Ohno-Shosaku et al., J Neurosci 22, 2002).3. These results suggest that endocannabinoids mediate target-specific retrograde signals, by which the postsynaptic neuronal activity influences the transmitter release from certain types of presynaptic terminals.