AUTHOR=Guirado Ramon , Perez-Rando Marta , Ferragud Antonio , Gutierrez-Castellanos Nicolas , Umemori Juzoh , Carceller Hector , Nacher Juan , Castillo-Gómez Esther TITLE=A Critical Period for Prefrontal Network Configurations Underlying Psychiatric Disorders and Addiction JOURNAL=Frontiers in Behavioral Neuroscience VOLUME=14 YEAR=2020 URL=https://www.frontiersin.org/journals/behavioral-neuroscience/articles/10.3389/fnbeh.2020.00051 DOI=10.3389/fnbeh.2020.00051 ISSN=1662-5153 ABSTRACT=

The medial prefrontal cortex (mPFC) has been classically defined as the brain region responsible for higher cognitive functions, including the decision-making process. Ample information has been gathered during the last 40 years in an attempt to understand how it works. We now know extensively about the connectivity of this region and its relationship with neuromodulatory ascending projection areas, such as the dorsal raphe nucleus (DRN) or the ventral tegmental area (VTA). Both areas are well-known regulators of the reward-based decision-making process and hence likely to be involved in processes like evidence integration, impulsivity or addiction biology, but also in helping us to predict the valence of our future actions: i.e., what is “good” and what is “bad.” Here we propose a hypothesis of a critical period, during which the inputs of the mPFC compete for target innervation, establishing specific prefrontal network configurations in the adult brain. We discuss how these different prefrontal configurations are linked to brain diseases such as addiction or neuropsychiatric disorders, and especially how drug abuse and other events during early life stages might lead to the formation of more vulnerable prefrontal network configurations. Finally, we show different promising pharmacological approaches that, when combined with the appropriate stimuli, will be able to re-establish these functional prefrontocortical configurations during adulthood.