Developmental Age Differentially Mediates the Calcium-Binding Protein Parvalbumin in the Rat: Evidence for a Selective Decrease in Hippocampal Parvalbumin Cell Counts

摘要: Local circuit GABAergic neurons, including parvalbumin (PV)-containing basket cells, likely play a key role in the development, physiology, and pathology of neocortical circuits. Regionally selective and well-defined decreases in PV have been described in human postmortem schizophrenic brain tissue in both the hippocampus and prefrontal cortex. Animal models of schizophreniform dysfunction following acute and/or chronic ketamine treatment have also demonstrated decreases in PV expression. Conflicting reports with respect to PV immunoreactivity following acute and chronic ketamine treatments in rodents question the utility of using PV as a biological marker of pathology-related dysfunction. The current literature lacks sufficient and systematic characterization of normative PV expression in pharmacologically and behaviorally naïve rodent tissue. In order to understand developmental changes in PV and its putative role in neuropathology, we examined the baseline distribution of the number of cells expressing this protein at distinct developmental ages. The present study examined PV cell counts across the septotemporal axis of the CA1, CA3, and dentate gyrus (DG) regions of the hippocampus, as well as within the retrosplenial, somatosensory, and prefrontal cortices, in 1-, 6-, and 12-month-old naïve rats. Our findings suggest that the hippocampal PV+ cell number significantly decreases as a function of age with considerable regional (CA1, CA3, and DG) and septotemporal variation, a finding that was specific to the hippocampus. Additionally, we observed a modest increase in PV cell number within the prefrontal (anterior cingulate) cortex, which is in line with findings indicating a delayed developmental maturation of this region. The present work highlights decreases in PV+ cell counts within the hippocampus across development, and points to the need for a greater understanding of the role of PV and local circuit developmental changes, as well as consideration of their development when modeling developmentally related neuropathological disorders (e.g. schizophrenia, autism).