|Alterations in Neocortical Neuron Excitability Associated with Fragile X
by Charles Cox, 9/1/2005
While it is clear that fragile X syndrome results from a single gene defect, the consequences of this alteration can produce a variety of changes in the nervous system. The circuit activity of neuronal
networks is ultimately influenced by the intrinsic excitability of individual neurons, and their
synaptic connectivity. Recent studies have indicated robust modifications in the dendritic structures of neurons in the fragile X conditions, but the functional signicance of these changes is unclear. Furthermore, multiple studies in the hippocampus have indicated alterations in synaptic plasticity
associated with fragile X, but less is known regarding alterations in the neocortex.
Our experiments are designed to determine whether there are alterations in the intrinsic excitability of individual neurons within the visual neocortex. We will use modern intracellular recording techniques to determine if there are alterations in intrinsic properties or synaptic transmission within neocortical
neurons. In addition, we will investigate alterations in long-term potentiation (LTP) within the neocortex, with an emphasis on metabotropic glutamate receptor mediated plasticity. Differences in these fundamental properties of neurons could greatly impact the cell's normal function and its ability to communicate with surrounding neurons, potentially providing possible explanations for neural deficits associated with fragile X syndrome.