Age- and Experience-Related Distribution of Parvalbumin-Expressing GABAergic Interneurons within the Hippocampus & Surrounding Cortices

Parvalbumin (PV)-expressing inhibitory interneurons are the most numerous GABAergic interneuron type in the neocortex and hippocampus (HPC). Selective reductions in PV interneurons are observed in cortical and limbic regions in postmortem human schizophrenic brain tissue. Reductions in PV expression are also observed in rodents following acute and/or chronic treatment with NMDAantagonists (e.g. ketamine). There are inconsistencies in the literature regarding age-related changes in PV expression in the HPC; some stating age-related decreases, no observed changes, and even increases in PV-immunoreactivity. These inconsistencies make it difficult to qualitatively and quantitatively evaluate changes observed in rodent models following NMDA-antagonist treatment. In order to provide a better baseline understanding of putative developmental changes in normal PV expression, the current study quantified 1) age-related changes in HPC and cortical PV expression in rats; 2) whether PV varied along the septotemporal axis of the HPC; and 3) regional changes in HPC PV expression. PV immunohistochemical methods were used to examine PV expression in hippocampal and adjacent neocortical regions in 1 and 6 month old naïve, as well as 24 month old behaviorally trained (radial water maze training), male Sprague-Dawley rats. Our main findings include: 1) specific regional differences (CA1, CA3, DG) across the septotemporal axis that varied by developmental age; 2) age-related decreases in PV expression in CA1 and DG (50-68% and 88-89% decrease from 1 – 6 months, respectively) in naïve rats; 12 and 3) A prominent increase in PV expression in the 24 month old rats that may be related to age or behavioral experience. These findings demonstrate developmental differences in the regional expression of PV, as well as potential behavioral and experiential increases in PV expression. Importantly, these baseline data provide key information for future work examining age-related differences in PV as a consequence of acute or chronic NMDA-antagonist