Wen-Biao Gan

Wen-Biao Gan, PhD
Principal Investigator
Feng Pan, PhD
Postdoctoral Fellow
New York University

FRAXA Awards:
  $45,000 in 2008 
  $40,000 in 2007 

 
In Vivo Imaging of Synaptic Abnormalities in a Mouse Model of Fragile X Syndrome

By Feng Pan 4/2007

Feng Pan

Fragile X syndrome (FXS) is the most common form of inherited mental retardation. Previous studies have revealed an overabundance of long and thin postsynaptic dendritic spines in the brains of FXS patients, suggesting that abnormal formation and plasticity of neuronal connections play important roles in behavioral and learning deficits associated with FXS.

Using a newly-developed transcranial two-photon imaging technique and a mouse model of FXS in which the fragile X mental retardation protein (FMRP) is knocked out, we will examine the development and dynamics of synapses by following individual postsynaptic dendritic spines and presynaptic axonal boutons over extended periods of time in living mouse cortex. We will determine, for the first time, whether and when abnormal pre- and postsynaptic structural plasticity occurs in the mouse model of FXS. In addition, we will determine whether abnormal structural plasticity of synapses can be reversed upon the acute and/or long-term treatment of drugs that have been shown to successfully alleviate behavior problems in fly and mouse models of FXS.

Together, the proposed study will provide new insight into the mechanisms underlying abnormal synaptic plasticity in FMRP deficient mice and a solid basis for developing new therapeutic interventions.