Role of sensory experience in the regulation of plasticity in the developing, adult and aging brain

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The long-term objective of my research program is to determine how sensory experience modulates brain plasticity in the developing, adult, and aging brain. My research plan for the next five years is divided into three main axes, each focusing on investigating specific factors that influence brain plasticity. The experiments proposed to combine state-of-the-art in-vivo electrophysiology, chemo and optogenetics, behavior, pharmacology, and histology in the rat primary auditory cortex (A1), a powerful system to study brain plasticity. Axis I. Determining how sensory input characteristics regulate plasticity in the developing, adult, and aging A1. We have previously demonstrated that the presence of auditory input patterns in the environment was necessary for the maturation of A1 circuits both at a functional and structural level. We have also shown that a prolonged absence of such patterns during adult life can induce plasticity in the adult A1 and ultimately lead to destabilization of auditory cortical maps. The main objective of this research Axis is to determine precisely the sound input characteristics, in quality and quantity that are necessary to induce A1 maturation during development or to induce plasticity in the mature A1. Axis II. Determining the contribution of parvalbumin-positive (PV+) neurons and somatostatin-positive (SOM+) neuron to A1 plasticity in the developing, adult and, aging rat. There is extensive work showing the importance of cortical inhibition in the regulation of cortical plasticity, whether during early development, during adulthood, and aging. The closure of the CP, for example, requires an increase in cortical inhibition. The main focus of Axis II is to determine how inhibitory interneurons, particularly PV+ and SOM+ cells, participate in the regulation of cortical plasticity and how they are related to age-related map instability. We will also determine if manipulating the activity of these cells can normalize the regulation of plasticity in the aging brain. Axis III: Identifying the regulating mechanisms of cross-modal plasticity. It is now well established that the visual cortex of blind individuals is repurposed to process other sensory inputs. For unknown reasons, this process known as cross-modal plasticity displays substantial inter-individual variability. In this research Axis, our goal is to determine in rat models of sensory deprivation how various levels of auditory enrichment and sensory experience modulates the crossmodal takeover of the deafferented cortex. The integrative research plan I propose will provide a rich training environment for a minimum of 15 students over the next five years. The scientific outcomes we anticipate will bring a novel in-depth understanding of the way sensory experience regulates brain plasticity and are likely to contribute to the development of new neuroplasticity-based therapeutic strategies.