Role of perineuronal nets in consolidating memory traces of early-life adversity – RE-OPEN

Early-life adversity (ELA) is amongst the strongest predictors of mental health issues, in particular depression. This psychopathological outcome is though to be partly mediated by altered trajectories in the development of brain areas crucial for the maturation of stable emotional phenotypes. The cellular underpinnings of these changes are however poorly understood. My preliminary findings indicate that in humans, ELA precipitates the recruitment of perineuronal nets (PNNs), a specialized form of extracellular matrix that regulates plasticity in part by stabilizing the connectivity and hindering the structural remodeling of neuronal networks. Based on these properties, my hypothesis is that the formation of PNNs consolidates aversive memories and experiences of ELA, sustaining psychopathological development. This will be tested in a mouse model of ELA, the juvenile social defeat stress, by investigating how degrading PNNs can impair the reactivation of neuronal ensembles participating in the encoding and the recall of the aversive memory, at the cellular and behavioural level, and prevent the negative behavioural outcome of ELA.