Chronic nicotine reverses age-related decline of interneuron markers in mouse auditory cortex.

Inhibition in central auditory pathways declines in old age, which contributes to age-related auditory processing deficits. In auditory cortex, most inhibitory interneurons can be identified by one of three marker proteins: parvalbumin (PV), somatostatin (SOM), or vasoactive intestinal peptide (VIP). About 10% of interneurons contain the α2 nicotinic acetylcholine receptor (α2 cells), and most of these are layer 5 Martinotti cells (α2-MCs). We examined the distribution of these four interneuron subtypes in auditory cortex of FVB mice, from young adult through old age, and the extent to which α2 cells express the marker proteins. We also examined the effects of chronic nicotine exposure (CNE) at older ages, as a step toward potential therapeutic applications. We found that the numbers of cells expressing PV, SOM and VIP, and α2-MCs, all declined with age, but total α2 cells did not. We also found that most (86%) α2 cells in young adult mice co-expressed SOM, but the co-expression declined sharply with age. Notably, CNE for three months-starting at age 9, 15, or 21 months-increased the numbers of cells with PV and VIP at 12, 18, and 24 months, respectively, to levels seen in young adults. CNE increased SOM interneurons only at 12 months and had no effect on the number of α2 cells. An analysis of immunofluorescence intensity in 12-month-old mice suggested that the increase in cell counts after CNE resulted from increased expression of marker protein, rather than de novo appearance of interneurons. Thus, CNE partly or fully reversed the age-related decline of interneuron-marker expression and may prove useful for treatment of age-related auditory processing deficits.