Role of auditory experience in the regulation of plasticity in the developing and adult 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 and adult brain. My research plan for the next five years is divided into three main axes, described below, each focusing on investigating specific factors that influence brain plasticity, as well as their consequences on behavior. The experiments proposed combine state-of-the-art in-vivo electrophysiology, behavior, pharmacology and histology in the rat primary auditory cortex (A1), a powerful system to study brain plasticity with which we have years of experience. **Axis I. Determining how auditory input statistics regulate plasticity in the developing and adult 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 showed 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. These findings demonstrate that auditory experience is a strong modulator of plasticity and indicate there must be a specialized brain mechanism that continuously monitors the level of patterned activity in A1. 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 induce plasticity in the mature A1. We will then determine whether parvalbumin positive cells, a specific group interneurons linked to A1 maturation might be involved in pattern detection and, if yes, whether manipulating their activity artificially could trigger or block A1 plasticity.**Axis II. Determining the role of experience on the selectivity of "top-down" modulation in A1. The sensitivity of A1 to various sounds is strongly modulated according to what we need to hear in the context of a specific task. This system is essential to improve the robustness of auditory processing in noisy situations or in the presence of competing auditory inputs. Growing correlational evidence in humans suggest that frontal cortical fields are involved in this top-down modulation. The main focus of Axis II is to use our rodent model and cortical inactivation techniques to determine if that is truly the case, and understand how auditory experiences and more specifically auditory training can modulate the strength and quality of A1-frontal interaction to improve the fidelity of auditory coding.**Axis III: Establishing the mechanisms of regulation of cross-modal plasticity. It is now well established that the visual cortex of blind individuals can under certain circumstance re-specialize into an auditory processing field. For unknown reasons, this process known as cross-modal plasticity displays substantial inter-individual variability. Correlational data in humans suggest that the quantity of residual visual and competing auditory inputs might be an important factor contributing to this variability. In this research Axis our goal is to determine in rats with different degree of blindness and living in various levels of auditory enrichment how sensory experience drives and modulates the crossmodal takeover of de-afferented cortex. **The integrative research plan we propose will provide a rich integrative training environment for a minimum of 15 students over the next five years. The experimental results we anticipate will bring a novel in-depth understanding of the way sensory experience regulates brain plasticity and are likely to contribute, as we have shown before to the development of new neuroplasticity-based therapeutic strategies for our population.