Extracellular Matrix Alterations Due to Early-Life Adversity: Implications for Auditory Learning in Male Sprague-Dawley Rats.

This study aimed to investigate the impact of early childhood chronic stress on the development of the brain extracellular matrix (ECM) and how alterations in the ECM following early-life adversity (ELA) affect auditory learning and cognitive flexibility. ELA was induced through a combination of maternal separation and neonatal isolation in male Sprague-Dawley rats, and the success of the ELA model was assessed behaviorally and biochemically. A cortex-dependent go/no-go task with two phases was used to determine the impact of ELA on auditory learning and cognitive flexibility. The effects of the ECM on cognition were tested via the enzymatic removal of the ECM. The molecular structure of the adult ECM was examined via immunohistochemistry. ELA impaired initial auditory learning but did not significantly affect cognitive flexibility. Hyase injection into the auditory cortex (ACx) restored initial learning. ELA rats display a reduced perineural net (PNN) and parvalbumin + cell density. Our findings reveal that ELA induces significant alterations in the ECM within the ACx, accompanied by impaired initial auditory learning. Although PNN density is already lower in ELA rats, degrading the ECM facilitates the repair of auditory learning. A reduced PNN number in ELA rats fails to enhance learning unless supplemented with Hyase injection.