Distribution of m1-m4 muscarinic receptor proteins in the rat striatum: light and electron microscopic immunocytochemistry using subtype-specific antibodies.

Muscarinic ACh receptors mediate complex and clinically important effects in the striatum. To better understand the roles of the different muscarinic receptor subtypes (m1-m4), we have determined the cellular and subcellular distribution of the m1-m4 receptor proteins in the rat neostriatum using subtype-specific antibodies and avidin-biotin-peroxidase immunocytochemistry for light and electron microscopy. m1 receptor protein is expressed in 78% of neurons and is enriched in spiny dendrites and at postsynaptic densities. A small number of m1-immunoreactive axon terminals were observed, all forming asymmetrical synapses. About 2.5% of striatal neurons express m2 receptor protein with reaction product evident, by light microscopy in scattered large oval neurons with enfolded nuclei and long aspiny dendrites. By electron microscopy, m2 immunocytochemistry labeled somata, aspiny dendrites, and many axon terminals. Most axon terminals containing m2 make symmetrical synapses with somata, and dendritic shafts and spines. In addition, many m2-immunoreactive axon terminals formed asymmetrical synapses with spines or dendrites. m3 receptor protein was not evident in somata by light microscopy but was present in a distinct population of small-caliber spiny dendrites as well as in axon terminals forming asymmetrical synapses with spines. m4 receptor protein was heterogeneously distributed in the neostriatum and localized to 44% of striatal cells. m4-positive neurons had the ultrastructural features of medium spiny neurons with reaction product particularly concentrated in spines, often at postsynaptic densities. Axon terminals containing m4 form asymmetrical synapses, primarily with spines. These findings indicate that the muscarinic receptor proteins occur in distinct populations of striatal neurons; that the receptor proteins concentrate postsynaptically at synapses, including many considered to be noncholinergic; that m2 is the predominant muscarinic autoreceptor in the striatum; and that each receptor subtype may be a presynaptic heteroceptor in the striatum modulating extrinsic striatal afferents.