Plasticity and variation in brain organization and behaviour

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Mammalian brains change throughout the course of a lifetime, but the impact of early life experience has the most profound effect on how the brain is constructed. Specifically, changes in connectivity and organization of the neocortex and the behavior it directs give mammals (humans included) enormous flexibility to adapt to novel environments. Such experience-based plasticity has been demonstrated by enhancing or depriving sensorimotor experience, which generally enlarges and shrinks corresponding body part representations, respectively. For example, trimming the whiskers of rats and mice causes the cortical whisker representation to shrink and that of the forelimb to grow. Training rodents to reach with their forelimbs enlarges the paw representation. The additional neural processing possible in larger representations is thought to underlie enhanced abilities of the corresponding body parts. Most studies of brain plasticity manipulate one variable at a time (e.g. whisker trimming or reach training). But outside of the laboratory, multiple factors together alter the brain and behavior. The complex interaction of factors shaping brains in the real world points to the need for several complementary lines of inquiry. My research program aims to understand how experience shapes the brain. In this proposal, our objectives are to: (1) Determine the extent to which a given genotype can produce variable cortical phenotypes, i.e., how much can the brain change in one lifetime? (2) Determine how multiple complementary changes in experience common in nature, but so far absent in the laboratory interact to shape brain organization. (3) Measure the magnitude of individual variation in sensorimotor skills and relate this to variation in brain organization. The techniques proposed here are well established, but will be implemented in new ways and combinations. This will be the first examination of neural plasticity combining complementary enhancement of one body part (forelimb) and deprivation of another (whiskers). Forelimb reach training will be far more pervasive and will begin far earlier than any previous study. Together these innovations address fundamental questions about the limits of brain plasticity, the impact of complex environments on brain organization, and the relationship between brain organization and skill. Our inquiries will contribute to neuroscientists' understanding of how brains develop and change. As well as being a fundamental question about the nature of humans and other mammals, how animals adapt to complex, changing environments has implications for their responses to climate change and other human impacts on the environment. For humans, the basic question of how changeable and variable the brain is has implications for education, health and societal attitudes about which parts of behavior are fixed and which are mutable.