Distribution of Nicotinic Receptors in the Human Hippocampus and Thalamus

Abstract

Neuronal nicotinic acetylcholine receptors consist of different subunits, alpha and beta, with different subtype arrangement corresponding to distinct pharmacological and functional properties. The expression of alpha 3, alpha 7 and beta 2 mRNA in the human brain was studied by in situ hybridization and compared to [3H]nicotine, [3H]cytisine and [125I]alpha-bungarotoxin binding in contiguous sections. The beta 2 probe showed a strong hybridization signal in the granular layer of the dentate gyrus and in the CA2/CA3 region of the hippocampus and in the insular cortex, and a signal of lower intensity in the subicular complex and entorhinal cortex. The alpha 3 probe showed strong hybridization in the dorsomedial, lateral posterior, ventroposteromedial and reticular nuclei of the thalamus, and a weak signal in the hippocampal region and in the entorhinal, insular and cingular cortex. The amount of alpha 7 mRNA was high at the level of the dentate granular layer and the CA2/CA3 region of the hippocampus, in the caudate nucleus and in the pulvinar and ventroposterolateral nuclei of the thalamus. [3H]Nicotine and [3H]cytisine binding appeared to be identical in anatomical distribution and relative intensity. It was high in the thalamic nuclei, the putamen and in the hippocampal formation in the subicular complex and the stratum lacunosum moleculare. The level of [125I]alpha-bungarotoxin binding was particularly high in the hippocampus and in the pyramidal cells of the CA1 region, but was relatively low in the subicular complex. Our data indicate that in the human brain nicotinic receptor subtypes have discrete distributions, which are in part different from those of other species.