M2-like receptors are located both presynaptically and postsynaptically. M2/3 receptors are expressed on presynaptic glutamatergic terminals [33], whereas M4 receptors are expressed postsynaptically in MSNs and have higher expression levels in striatonigral neurons than those in striatopallidal neurons [20]. Presynaptically, M2/3 receptor activation can control the excitatory inputs by reducing glutamatergic transmission [33,34,35,36,37]. This presynaptic inhibition is mediated by inhibition of presynaptic Cav2 channels and decrease in probability of release, similar to mGluR2 and GABAB receptor signaling. This modulation occurs rapidly and causes a reduction in glutamate release at corticostriatal and thalamostriatal terminals on both striatonigral and striatopallidal MSNs [15].
