Prenatal Protein Malnutrition Increases Activation of Parvalbumin Interneurons but Decreases Overall Activation in the Prefrontal Cortex of Adult Rats

Prenatal protein malnutrition (PPM) leads to an imbalance in inhibitory processes increasing the risk of neurological disorders such as attention deficits. Previous studies using 2-deoxyglucose (2DG) as a marker of metabolic activity showed that PPM rats have an overall decrease in baseline activation in the prefrontal cortex (PFC). Interestingly, studies using the immediate early gene cFos as a marker for cellular activation showed an increase rather than a decrease in the number of cFos neurons in PPM rats after exposure to restraint stress. In this study we used both 2DG and immunohistochemistry (IHC) techniques to investigate the specificity of these results at both regional and cellular levels. We extended the 2DG analysis beyond the PFC to include the basal ganglia, cingulate, hippocampus, thalamus and other regions and used double-label IHC to determine if Parvalbumin (Parv) positive GABAergic neurons were also cFos positive. Results showed that PPM decreases in 2DG activation were limited to the medial PFC subfields associated with attention. At the cellular level, the number of cFos positive neurons double labeled with Parv (i.e. GABAergic interneurons) was significantly higher in the PFC of PPM rats than controls. These results indicate that the PFC is particularly vulnerable to PPM and also suggest that hyper-activation of inhibitory interneurons is dampening overall activity in the PFC.