Nicotinic acetylcholine receptors in rat cochlear nucleus: [¹²⁵I]- α-bungarotoxin receptor autoradiography and in situ hybridization of α7 nAChR subunit mRNA

The cochlear nucleus (CN) is the first site in the central nervous system (CNS) for processing auditory information. Acetylcholine in the CN is primarily extrinsic and is an important neurotransmitter in efferent pathways thought to provide CNS modulation of afferent signal processing. Although muscarinic acetylcholine receptors have been studied in the CN, the role of nicotinic receptors has not. We examined the distribution of one nicotinic acetylcholine receptor subtype, the α-bungarotoxin receptor (αBgt), in the CN. Quantitative autoradiography was used to localize receptors and in situ hybridization was used to localize α7 mRNA in CN neurons that express the αBgt receptor. Binding sites for αBgt are abundant in the anterior ventral, posterior ventral, and dorsal divisions of the CN, and receptor density is low in the granule cell layer and interstitial nucleus. Heterogeneity in CN subregions is described. Four distinct patterns of αBgt binding were observed: (1) binding over and around neuronal cell bodies, (2) receptors locally surrounding neurons, (3) dense punctate binding in the dorsal CN (DCN) not associated with neuronal cell bodies, and (4) diffuse fields of αBgt receptors prominent in the DCN molecular layer, a field underlying the granule cell layer and in the medial sheet. The perikaryial receptors are abundant in the ventral CN (VCN) and are always associated with neurons expressing mRNA for the receptor. Other neurons in the VCN also express α7 mRNA, but without αBgt receptor expression associated with the cell body. In general, αBgt receptor distribution parallels cholinergic terminal distribution, except in granule cell regions rich in cholinergic markers but low in αBgt receptors. The findings indicate that αBgt receptors are widespread in the CN but are selectively localized on somata, proximal dendrites, or distal dendrites depending on the specific CN subregion. The data are consistent with the hypothesis that descending cholinergic fibers modulate afferent auditory signals by regulating intracellular Ca²⁺ through αBgt receptors.