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Mechanisms of age- and experience-dependent neural plasticity and behavior

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PROJECT SUMMARY. We have made astounding progress in our understanding of how experience triggers change in the adult nervous system for learning and long-term memory formation. Learning in developing systems highlights a feature of learning often overlooked: the ability to learn from the same experience is not always equivalent. This means that properties of the brain can change such that sometimes they can learn and other times they cannot. Because early life experience can have profound and lasting effects on typical and atypical cognitive function and behavior, it is essential to understand what neural characteristics modulate experience-dependent plasticity. Learning requires integrated processes of receptivity and responsivity; a neural circuit must be established yet flexible such that it is possible to initiate experience-dependent change and effectively respond to experience. It is difficult to examine these features in adults, and with existing methodologies that limit integration of these two levels of cellular learning. Here, we propose a strategy that takes advantage of a model that undergoes extreme fluctuations in the ability to learn. A juvenile male zebra finch songbird can only form the memory of another ?tutor? bird?s song, which he uses to structure his own song, during 35 days in development. This occurs despite constant, daily exposure to singing birds. With this system as part of the experimental toolset, we can assay chromatin landscapes and enhancers in a brain area required for tutor song memorization to track baseline changes in cellular status that set receptivity. We can also use biochemical assays to selectively identify proteins actively synthesized after song experience. These two properties combined, in the context of birds we know can or cannot memorize tutor song, will provide unique, integrated maps of cell subtypes and molecular processes that promote and limit the ability to learn.
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