M1 receptor activation also suppresses inhibitory synaptic transmission in MSNs through modulating the endocannabinoid system [47]. Tonic ACh from cholinergic interneurons constitutively enhances depolarization-induced release of endocannabinoids from MSNs. The retrogradely released endocannabinoids cause suppression of inhibitory synaptic currents in MSNs through presynaptic CB1 receptors. Muscarinic receptor activation also significantly enhances depolarization-induced suppression of inhibition (DSI) in MSNs [47]. Pharmacological manipulation that elevates ambient ACh level or suppresses spontaneous firing of cholinergic interneurons can enhance or reduce DSI, respectively.
