Cellular Basis for Learning Impairment in Fragile X Syndrome
Technical Report,01 Aug 2014,31 Jul 2015
University of Illinois at Chicago Chicago United States
Pagination or Media Count:
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 third 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 how synaptic plasticity is disrupted in fragile X model mice. 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 regulation of neurogenesis in the hippocampus and olfactory bulb as well as to determine the effect of FMRP deficiency on inhibitory synaptic transmission in the olfactory cortex. 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.