Behavioral effects of direct in vivo reprogramming of reactive glial cells into interneurons in the medial prefrontal cortex

Abstract

The medial prefrontal cortex (mPFC) participates in the neurobiology of stress responses and in the pathophysiology of anxiety- and depression-like phenotypes. The activity of GABAergic interneurons modulates mPFC function and controls the behavioral responses coordinated by this brain region. Interestingly, reactive glial cells, particularly NG2 glial cells, are a potential source of new GABAergic interneurons in the adult brain. Recently, studies have introduced the possibility of directly reprogramming reactive glial cells into GABAergic interneurons in vivo by inducing the expression of transcription factors via a retroviral vector that stably transfects proliferative cells only. Being NG2 glial cells the main proliferative cells in most brain regions, the injection of these retroviral vectors will target mainly this cell type. Therefore, the goal of this project is to evaluate the behavioral effects of the direct in vivo reprogramming of reactive glial cells into GABAergic interneurons in the mPFC of mice. We will use C57Bl/6J male mice that will receive the intra-mPFC injection of the retroviral vectors that induce glia-to-interneuron reprogramming. Six-to-eight weeks later, mice will be submitted to tasks to evaluate anxiety- and depression-like behaviors. We will use the behavioral tasks novelty suppressed feeding and tail suspension test. The glial-to-interneuron reprogramming efficacy will be confirmed labeling transfected cells with interneuron molecular markers through immunohistochemistry. (AU)