The nicotinic acetylcholine receptor subtypes and their function in the hippocampus and cerebral cortex.

Nicotinic acetylcholine receptors (nAChRs) are widely distributed in the central nervous system and have been implicated in multiple behavioral paradigms and pathological conditions. Nicotinic therapeutic interventions require an extensive characterization of native nAChRs including mapping of their distribution and function in different brain regions. Here, we describe the roles played by different nAChRs in affecting neuronal activity in the hippocampus and cerebral cortex. At least three distinct functional nAChR subtypes (alpha 7, alpha 4 beta 2, alpha 3 beta 4) can be detected in the hippocampal region, and in many instances a single neuron type is found to be influenced by all three nAChRs. Further, it became clear that GABAergic and glutamatergic inputs to the hippocampal interneurons are modulated via different subtypes of nAChRs. In the cerebral cortex, GABAergic inhibition to the layer V pyramidal neurons is enhanced predominantly via activation of alpha 4 beta 2 nAChR and to a minor extent via activation of alpha 7 nAChR. Such diversity offers pathways by which nicotinic drugs affect brain function.