@article {Cisneros-FrancoENEURO.0051-18.2018, author = {J. Miguel Cisneros-Franco and Lydia Ouellet and Brishna Kamal and Etienne de Villers-Sidani}, title = {A Brain without Brakes: reduced Inhibition Is Associated with Enhanced but Dysregulated Plasticity in the Aged Rat Auditory Cortex}, elocation-id = {ENEURO.0051-18.2018}, year = {2018}, doi = {10.1523/ENEURO.0051-18.2018}, publisher = {Society for Neuroscience}, abstract = {During early developmental windows known as critical periods (CP) of plasticity, passive alterations in the quality and quantity of sensory inputs are sufficient to induce profound and long-lasting distortions in cortical sensory representations. With CP closure those representations are stabilized, a process requiring the maturation of inhibitory networks and the maintenance of sufficient GABAergic tone in the cortex. In humans and rodents however, cortical inhibition progressively decreases with advancing age, raising the possibility that the regulation of plasticity could be altered in older individuals. Here we tested the hypothesis that aging results in a destabilization of sensory representations and maladaptive dysregulated plasticity in the rat primary auditory cortex (A1). Consistent with this idea, we found that passive tone exposure is sufficient to distort frequency tuning in the A1 of older but not younger adult rats. However, we also found that these passive distortions decayed rapidly, indicating an ongoing instability of A1 tuning in the aging cortex. These changes were associated with a decrease in GABA neurotransmitter concentration and a reduction in parvalbumin and perineuronal net expression in the cortex. Finally, we show that artificially increasing GABA tone in the aging A1 is sufficient to restore representational stability and improve the retention of learning.Significance Statement In this study, we examined brain plasticity in the auditory cortex of young adult and older adult rats in the context of different types of auditory stimulation and training. Surprisingly, older brains retained an equal or even higher potential for plasticity compared to young adults. In older brains, however, changes elicited by auditory stimulation and training were rapidly lost, suggesting that such increased plasticity might be detrimental as the older brains were unable to consolidate these changes. This increased but poorly regulated plasticity was associated with a reduction in cortical inhibition which normally maintains the stability of sensory representations in the young adult brain. Importantly, increasing inhibition artificially with clinically available drugs restored stability and improved the retention of learning.}, URL = {https://www.eneuro.org/content/early/2018/08/21/ENEURO.0051-18.2018}, eprint = {https://www.eneuro.org/content/early/2018/08/21/ENEURO.0051-18.2018.full.pdf}, journal = {eNeuro} }