Grant: Operating Grant

The brain is a fundamentally plastic organ. This plasticity allows us to adapt to almost any environment and recover after a neurological injury such as a stroke, for example. The plastic potential of the brain is maximal during early development when learning can occur rapidly with less effort than during adulthood. While extensive plasticity and learning is still possible in young adults, for reasons still unknown, this potential significantly drops as we reach old age. This is unfortunate as older individuals are also more likely to suffer from a neurological injury. Decades of studies performed in animal models have revealed several of the fundamental mechanisms responsible for the regulation brain plasticity. Brain inhibition is one of those elements and its presence is essential for the specificity and stability of the plastic changes associated with learning. In humans and most animal models aging is almost always associated with a substantial reduction in brain inhibition. Based on this evidence, we posit that this loss of inhibition is at the origin of the reduction in plasticity seen in older individuals. More specifically we hypothesize that the aging brain retains significant plastic potential in itself but that reduced inhibition results in a dysfunction of its mechanisms of regulation. Proving this hypothesis would imply that simple interventions aimed at boosting brain inhibition could help improve the resilience and learning potential of the aging brain. To make this determination, we will use a well-established model to study the regulation of plasticity and aging, the rat auditory cortex. First we will expose rats of different ages to sounds and auditory training known to induce plasticity in a very specific fashion. Then, we will manipulate inhibitory circuits in the brain to understand how plasticity is failing with aging and how it can potentially be recovered.