LIGHT AND ELECTRON-MICROSCOPIC STUDY OF M2 MUSCARINIC ACETYLCHOLINE-RECEPTOR IN THE BASAL FOREBRAIN OF THE RAT

The m2 muscarinic acetylcholine receptor gene is expressed at high lev els in basal forebrain, but the paucity of information about localizat ion of the encoded receptor protein has limited the understanding of c ellular and subcellular mechanisms involved in cholinergic actions in this region. The present study sought to determine the cellular locali zation of m2 protein, its relationship to cholinergic neurons, and its pre- and postsynaptic distribution in the rat medial septum-diagonal band complex using immunocytochemistry with polyclonal rabbit antibodi es and a newly developed rat monoclonal antibody specific to the m2 re ceptor. Light microscopic colocalization studies demonstrated that m2 was present in a subset of choline acetyltransferase immunoreactive ne urons, in choline acetyltransferase-negative neurons, and in more neur opil elements than was choline acetyltransferase. Intraventricular inj ections of 192 IgG-saporin, an immunotoxin directed to the low-affinit y nerve growth factor receptor, resulted in depletion of choline acety ltransferase-immunoreactive neurons in the medial septum-diagonal band complex, whereas m2 immunoreactivity in neurons and in the neuropil w as unchanged. By electron microscopy, m2 receptor in medial septum-dia gonal band complex was localized to the plasmalemma of a small populat ion of small to medium-sized neurons, and it was also found in dendrit es, axons, and axon terminals in the neuropil. Neurons expressing m2 i mmunoreactivity received synaptic contacts from unlabelled axon termin als. A small distinct subpopulation of large neurons, unlabelled by m2 immunoreactivity, received synaptic contacts from m2-immunoreactive t erminals. Thus, m2 receptor is situated to mediate the local effects o f acetylcholine on basal forebrain cholinergic and noncholinergic neur ons and, also, at both pre- and postsynaptic sites. (C) 1995 Wiley-Lis s, Inc.