Jastyn A. Pöpplau and Ileana L. Hanganu-Opatz Institute of Developmental Neurophysiology, Center for Molecular Neurobiology, Hamburg Center of Neuroscience (HCNS), University Medical Center Hamburg-Eppendorf, Hamburg 20246, Germany Correspondence: jastyn.poepplauzmnh.uni-hamburg.de; hangopzmnh.uni-hamburg.de

The prefrontal cortex is considered as the site of multifaceted higher-order cognitive abilities. These abilities emerge late in life long after full sensorimotor maturation, in line with the protracted development of prefrontal circuits that has been identified on molecular, structural, and functional levels. Only recently, as a result of the impressive methodological progress of the last several decades, the mechanisms and clinical implications of prefrontal development have begun to be elucidated, yet major knowledge gaps still persist. Here, we provide an overview on how prefrontal circuits develop to enable multifaceted cognitive processing at adulthood. First, we review recent insights into the mechanisms of prefrontal circuit assembly, with a focus on the contribution of early electrical activity. Second, we highlight the major reorganization of prefrontal circuits during adolescence. Finally, we link the prefrontal plasticity during specific developmental time windows to mental health disorders and discuss potential approaches for therapeutic interventions.