Neuronal Nicotinic Acetylcholine Receptor Expression, Aging and Mouse Strain-Specific Hippocampal Cytoarchitecture

ABSTRACT

The differing response by individuals to nicotine reflects the biological outcome of a combination of genetic and environmental factors. Because nicotine imparts its effects through interacting with neuronal nicotinic acetylcholine receptors (nAChR), and mice of different inbred strains differ in their responses to nicotine; mice afford an excellent model for experimentally dissecting the biology of these varied responses. To begin this investigation, we compared the expression of nAChR subunits α3, α4, α5, α7, β2 and β4 in the dorsal hippocampus between 8 mouse strains that differ in their response to nicotine in defined ways. In terms of neuronal distribution, all nAChR subunits co-localized with glutamic acid decarboxylase (GAD) positive interneurons, and heterogeneity in nAChR subunit expression defines four interneuron subgroups. An unexpected finding was that nAChRs are also expressed by astrocytes in a mouse strain¬specific manner and their occurrence varies inversely with nAChR+ interneurons. This relationship is dynamic during the animal’s life span where aged animals exhibit increased nAChR+ astrocyte/interneuron ratios. These findings reveal a complex interplay between genetic and developmental factors that individualize the expression of this modulatory neurotransmitter system in the mammalian nervous system, and would likely customize the response to nicotine.