The five muscarinic receptors that have been identified can be grouped into two families. The M1-like receptors (M1 and M5) are coupled to Gq/11. Their activation will increase intracellular Ca2+ mobilization and activate phospholipase C (PLC) and protein kinase C (PKC). M2-like receptors (M2, M3 and M4) activate Gi/o proteins, which reduce c-AMP concentration and inhibit Ca2+ channels. Within the striatum, M1 and M4 are the major muscarinic receptors expressed in MSNs and NPY releasing interneurons, with M4 being overexpressed in striatonigral MSNs [19,20]. Furthermore, M2 and M3 receptors are located on presynaptic glutamatergic terminals. Additionally M2 and M4 receptors exist on cholinergic neurons acting as autoreceptors [5, 19]. Ionotropic nicotinic ACh receptors are expressed on glutamatergic and dopaminergic terminals as well as PV expressing interneurons but are absent in MSNs [21]. Therefore, in this review, we only discuss the muscarinic signalling in the striatum.
