Imbalance of immunohistochemically characterized interneuron populations in the adolescent and adult rodent medial prefrontal cortex after repeated exposure to neonatal separation stress

Experimental studies in various animal models have revealed convincing evidence that stressful experience during early developmental periods produces a variety of behavioral, neuroanatomical and endocrine alterations, which are reminiscent of human mental disorders such as depression and various types of anxiety disorders. Since these mental disorders are assumed to be associated with altered GABAergic inhibition in cortical and subcortical brain regions, the current study tested the hypothesis that early postnatal adverse emotional experience (separation stress) interferes with the establishment and functional maturation of distinct inhibitory interneuron populations in different subregions of the medial prefrontal cortex (mPFC) of the precocious rodent degu (Octodon degus). At the age around puberty early stressed animals displayed significantly lower densities of calbindin-D28k-immunoreactive interneurons in the anterior cingulate (down to 79%) and in the precentral medial (down to 64%) subregions of the mPFC compared with age-matched unstressed controls. At this age the densities of two other interneuron types characterized by their expression of the calcium-binding proteins parvalbumin or calretinin remained at control levels. In adulthood, i.e. after an extended period without stress exposure, the density of calbindin-D28k-immunoreactive interneurons in the stressed animals was back to control numbers, whereas parvalbumin-immunoreactive interneurons displayed significantly elevated density in the anterior cingulate (up to 138%) and in the precentral medial cortex (up to 137%) of the stressed animals. In both age groups the density of calretinin- and corticotropin releasing hormone-immunoreactive interneurons did not differ between stressed and control animals, and the prelimbic and infralimbic subregions of the medial prefrontal cortex remained unaffected by stress experience. These results confirm that early adverse emotional experience induces long lasting age-, region- and neuron-specific imbalance of inhibitory systems in some, but not all subregions of the medial prefrontal cortex of the degu.