Distribution of Nicotinic Subtypes in Human Brain

The distribution of high-affinity nicotine and alpha-bungarotoxin receptors has been compared in a number of human brain areas and related to the available data on receptor subtype mRNA expression. Nicotine binding is high in the thalamus, striatum, and substantia nigra pars compacta, and although not generally high in the hippocampal formation, it is concentrated in the entorhinal cortex, the subicular complex, and the stratum lacunosum moleculare. Nicotine binding is relatively low in the cerebral cortex, but it demonstrates varied patterns of distribution in different areas. Nicotine binding is also present in the cerebellar cortex and dentate nucleus. Nicotine binding in the thalamus corresponds to alpha 3 expression, but at variance to data from rodents, there is little evidence of beta 2 mRNA in this brain area. By contrast, there is beta 2 mRNA but not alpha 3 mRNA in the striatum. In the hippocampal formation both alpha 3 and beta 2 mRNAs are expressed, but the pattern of distribution does not resemble nicotine binding, only reaching moderate levels in the dentate granule cell layer and in the CA3 region. In the neocortex, alpha 4 expression is more widely distributed than alpha 3, but both are associated with pyramidal neurons. The distribution of nicotine binding, concentrated in brain areas gating multimodal inputs and often uncorrelated with cholinergic innervation, suggests a neuromodulatory role, possibly facilitating glutamatergic transmission. The distribution of alpha-bungarotoxin binding is different from that of nicotine in the hippocampal formation, being highest in the CA1 region and the dentate granule cell layer, but similar to nicotine binding in the substantia nigra pars compacta.(ABSTRACT TRUNCATED AT 250 WORDS)