While stress is an essential physiological response, exposure to chronic stress (CS) represents a major risk for various mental illnesses. CS has wide effects in the brain, but certain regions are particularly vulnerable. In the prefrontal cortex (PFC), CS disrupts neuronal communication and alters PFC-dependent functions, yet little is known about the mechanisms linking CS to these alterations. We suggest that increased levels of miR-186-5p – a modulatory genetic sequence that is induced by CS – may be a culprit for such effects, by reducing the levels of critical proteins for neuronal communication. We will study how stress-increased miR-186-5p alters neurotransmission and seek to find novel targets of miR-186-5p that may contribute to such defects. We will also study if reverting miR-186-5p levels can ameliorate the neuronal and behavioral deficits induced by CS. Finally, we will study if miR-186-5p is implicated in the known sex differences in the brain’s cognitive response to CS.