On the postsynaptic side, M4 receptor activation inhibits Cav2 channels and therefore shapes the spiking and up-state transitions in MSNs [5,31,32]. Although M4 receptor modulation is readily seen in nearly all MSNs, M4 receptors are expressed at higher levels in striatonigral MSNs [20]. The function of this imbalance is still not understood. It is likely that M4 receptor activation, together with DA signaling, produces differential modulations in striatonigral and striatopallidal MSNs. The muscarinic receptor signaling mechanisms outlined here are summarized in Figure 1.
