Cellular Basis for Learning Impairment in Fragile X Syndrome
Annual rept. 1 Aug 2013 - 31 Jul 2014
ILLINOIS UNIV AT CHICAGO
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This research combines behavioral, electrophysiological, and molecular approaches to elucidate the cellular basis for learning impairment in Fragile X Syndrome FXS, using olfactory learning in Fmr1-KO mice 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 second year of support were directed toward establishing a method to specifically upregulate neurogenesis in adult fragile X mice, test fragile X mice for learning deficits in hippocampal-independent tasks, and determine if learning affects NMDA receptor trafficking to synapses. 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 aging 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.
- Genetic Engineering and Molecular Biology
- Medicine and Medical Research