Fragile X syndrome is the most common inherited cause of mental retardation. The disorder is caused by mutation in a gene, FMR1, that encodes the fragile X mental retardation protein (FMRP). How loss of FMRP produces mental retardation is not known. FMR1 knockout mice have been produced, providing a mouse model for fragile X syndrome. The experiments proposed in this application will use the mouse olfactory system to investigate the normal function of FMRP and the consequences of the protein's absence in knockout mice. FMRP is normally expressed in olfactory brain structures. The project has three specific aims. First, behavioral analyses will be conducted to determine how lack of FMRP results in impairment of memory formation for olfactory information. Second, electrophysiological methods will be used to determine how absence of FMRP alters synaptic function and synaptic plasticity in the primary olfactory cortex. Third, olfactory stimulation and learning paradigms will be used to determine how expression of FMRP is regulated by neuronal activity in the olfactory system. The results of these studies should provide new information regarding the function of FMRP in the normal brain and may identify behavioral or physiological functions that are reliably disrupted in mice lacking this important protein. Such new information would be vital for evaluating novel treatment strategies for a class of developmental disabilities. ? ?
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