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Cellular Basis for Learning Impairment in Fragile X Syndrome

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Annual rept. 1 Aug 2012-31 Jul 2013

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This research combines behavioral, electrophysiological, and molecular approaches to elucidate the cellular basis for learning impairment in a mouse model for fragile X syndrome FXS, using olfactory learning as a model system. We hypothesize that FMRP, the protein missing in FXS, participates in two aspects of circuit function that are critical to learning synaptic plasticity and the generation and survival of new neurons in the adult brain. Efforts in the first year of support were directed to laying the groundwork for the experimental studies of the project, which we expect to complete in years two and three. Colonies of mice with the needed mutations have been established and all of the personnel for the studies are in place and trained. Significant advances have been made in the establishment of behavioral paradigms to test both hippocampal -dependent and - independent forms of olfactory learning. Experimental paradigms have also been refined for the study of neurogenesis in the olfactory bulb, glutamate receptor expression as it relates to olfactory learning in olfactory cortex and hippocampus, and the effects of age on glutamate receptor expression. These studies are likely to advance our understanding of intellectual disability and autism in addition to the specific condition of fragile X syndrome. This knowledge will be necessary for the development of rational strategies for prevention and treatment of cognitive impairments from a variety of causes.

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  • Medicine and Medical Research

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