Prefrontal cortex development and its implications in mental illness

The medial prefrontal cortex (mPFC) plays an essential role in cognition and emotional regulation. The mPFC undergoes an extended development that is regulated by both genetic programs and activity-dependent processes. During this time, experiences feedback on developing mPFC circuits, allowing individuals to develop nuanced, age-appropriate responses to their environment. However, this protracted development also opens an extended window when adverse experiences such as neglect or maltreatment can alter the trajectory of mPFC development, leading to the emergence of mental health disorders like anxiety and depression. These disorders are characterized by excessive avoidance of perceived threats and impaired emotional regulation. These behavioral functions are encoded in the activity of mPFC neural circuits, particularly in mPFC connections with limbic centers like the basolateral amygdala and nucleus accumbens. To understand how mental health disorders emerge, it is critical to understand how frontolimbic circuits typically develop, and how early life adversity can alter their development. Here we review recent studies that examined the synaptic, cellular, and circuit development of frontolimbic circuits and the underlying molecular and activity-dependent mechanisms. We then review studies that measured the effects of early life stress on mPFC maturation and discuss the implications for therapeutic strategies.