CODISTRIBUTION OF NICOTINIC ACETYLCHOLINE-RECEPTOR SUBUNIT ALPHA-3 AND BETA-4 MESSENGER-RNAS DURING RAT-BRAIN DEVELOPMENT

We have used in situ hybridization to characterize the ontogeny of alp ha 3 and beta 4 nicotinic acetylcholine receptor (nAChR) subunit mRNA expression in rat brain. Transcripts for both subunits were detected i n embryonic brain, although overlapping expression of alpha 3 mRNA was only evident in areas of strong beta 4 mRNA expression including the medial habenula, locus coeruleus, the cerebellar primordium, and sever al motor and sensory brainstem nuclei. During the perinatal period, th e independent expression of alpha 3 mRNA declined, and greater corresp ondence in the temporal and spatial expression of alpha 3 and beta 4 s ubunit mRNAs emerged. In general, beta 4 mRNA expression preceded that of alpha 3 mRNA by I to 2 days. Overlapping expression patterns were transiently detected in the caudate putamen, basal forebrain, frontal and visual cortices, and in the CA3 field of hippocampus. Codistributi on that lasted throughout development and into adulthood was noted in a number of brain areas, including the retrosplenial cortex, subiculum , medial habenula, interpeduncular nucleus, locus coeruleus, and brain stem motor nuclei. In many of these regions, alpha 5 subunit mRNA was also expressed. Colocalization of alpha 3 and beta 4 mRNAs with cholin e acetyltransferase mRNA was detected in cholinergic neurons of the br ainstem motor nuclei, nucleus ambiguus, dorsal motor nucleus of the va gus, motor trigeminal nucleus, and facial nucleus, but not in most for ebrain cholinergic cells. The extensive correspondence in temporal and spatial distribution of alpha 3 and beta 4 mRNAs throughout postnatal brain development suggests that these subunits may be coordinately re gulated and may form functional neuronal nAChRs with significant devel opmental roles. (C) 1997 Wiley-Liss, Inc.