抄録
Endocannabinoids (eCBs) are released from postsynaptic neurons, act retrogradely onto presynaptic cannabinoid CB1 receptors and cause transient suppression of transmitter release in various regions of the brain. The striatum contains a moderate level of CB1, and its function is regulated by the activity of cholinergic interneurons. In the present study, we examined how eCBs signaling interacted with the cholinergic system and modulated synaptic transmission in the striatum. We made whole-cell recording from medium spiny (MS) neurons and recorded inhibitory postsynaptic currents (IPSCs) in striatal slices from C57BL/6 mice (P15-21). We found that mAChR agonist triggered eCB-mediated suppression of IPSCs, and potently enhanced depolarization-induced, eCB-mediated suppression of IPSCs (DSI). Both effects were blocked by an M1-preferring antagonist, pirenzepine, and by postsynaptic infusion of GDP-β-S, and were absent in M1 knockout mice, indicating that postsynaptic M1 receptor is required. Magnitude of DSI was significantly reduced by the suppression of cholinergic interneuron activity, whereas it was enhanced by inhibiting choline esterase. These results indicate that depolarization-induced eCB release from MS neurons is persistently upregulated by ambient ACh through M1 receptors. [J Physiol Sci. 2007;57 Suppl:S8]
