Yu Zhang, Ph.D.

Andreas Frick, Ph.D., Principal Investigator
Yu Zhang, Ph.D., Postdoctoral Fellow NeuroCentre Magendie
Bordeaux, France

FRAXA Awards:
  $45,000 in 2010

by Andreas Frick, 4/2010

The mammalian neocortex is central for processes as diverse as sensory information processing, perception or control of motor activity, and cortical defects have devastating neurological and psychiatric consequences. In humans, the consequences of Fragile X Syndrome include hypersensitivity to sensory stimuli, autistic behavior, seizures, and learning and memory deficits.

Ion channel defects (channelopathies) are increasingly being recognized as a crucial feature of many central nervous system disorders, but have—with the exception of few studies—not been implicated in Fragile X Syndrome. The mRNAs of several ion channel subunits are regulated by FMRP. Ion channels strongly determine the properties of dendrites, the ‘brains’ of neurons regulating information processing, information storage, and the action potential output of these neurons and thereby of the entire neuronal circuit. Thus, any change in the expression pattern and properties of ion channels will alter these parameters.

Data from our own lab indeed strongly suggest significant changes in the dendritic function of neocortical neurons of Fmr1KO mice. Based on these data and other studies we therefore hypothesize that alterations in ion channel function are a crucial feature of Fragile X Syndrome, and that these alterations might provide “drugable” targets for new therapeutic strategies treating Fragile X Syndrome and Autism Spectrum Disorders. Strong focus of our project will be given at aiming to rescue dendritic information processing in vitro and in vivo using existing and novel drugs. The concept of ‘channelopathy’ promises new avenues for therapeutic treatment and a better understanding of Fragile X Syndrome and Autism Spectrum Disorders in general.