University of California, Irvine 3119 Gillespie Neuroscience Res Fac Mail Code: 4292 Irvine, CA 92697
Fragile X (FX) syndrome and Down Syndrome ((DS) are developmental intellectual disability disorders, and both are characterized by abnormalities in the dendritic spines of cortical pyramidal cells. Dendritic spines are small protrusions on a neuron’s dendrite that receive input from other cells and are the site for synaptic strength and plasticity. Our work utilizes mouse models of both FX (Fmr1 knockout) and DS (Ts65Dn) to investigate how synaptic mechanisms that promote learning and memory are perturbed in these disorders. In particular, we have shown that Fmr1 knockout mice have deficient hippocampal Long Term Potentiation (LTP), the presumable cellular substrate of memory, and learning deficits. Moreover, we have found that signaling pathways that regulate the actin cytoskeleton in hippocampal dendritic spines are selectively perturbed in Fmr1 knockouts. Current studies are extending this work to evaluate the same signaling pathways in the Ts65Dn model of Down syndrome and in human DS biopsy cortical tissue to determine if both FX and DS share common defects.