Development of muscarinic receptor subtypes in the forebrain of the mouse.

Cholinergic mechanisms are involved in the regulation of developmental events in the nervous system. Muscarinic cholinergic receptors are thought to be the predominant mediator of cholinergic neurotransmission in the forebrain; however, their developmental role is less well understood. The present study takes advantage of subtype-specific antibodies to muscarinic receptor proteins to investigate the cellular localization of the subtypes in developing mouse forebrain. Receptor protein expression was assessed between postnatal day (PND) 5 and adulthood by immunocytochemical methods with antibodies to m1, m2, and m4 receptors, the most abundant subtypes in rodent brain. We have found dramatic developmental changes in the distribution of all three receptors. In the adult mouse, m1 and m2 receptor immunoreactivity displayed complementary staining patterns in most forebrain areas with m4 sharing similarities in pattern with both m1 and m2. Furthermore, each receptor was expressed transiently in gray matter areas or fiber bundles at various developmental stages. The m4 receptor was also expressed in developing blood vessels. Such transient immunoreactivity was usually associated with times and areas of dynamic morphogenesis, thus suggesting distinct roles for the receptor subtypes in ontogenetic events.