| In Vivo Imaging of Synaptic Abnormalities in a Mouse Model of Fragile X Syndrome
By Feng Pan, 4/1/2007
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.
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