Environmental enrichment results in increased levels of Fmrp in brain and increased dendritic complexity. The present experiment evaluated activity-dependent increases in Fmrp levels in the motor cortex in response to training on a skilled forelimb reaching task in the CGG KI mouse model of the fragile X premutation. Fmrp, Arc, and c-Fos protein levels were quantified by Western blot in the contralateral motor cortex of mice following training to reach for sucrose pellets with a non-preferred paw and compared to levels in the ipsilateral motor cortex. After training, all mice showed increases in Fmrp, Arc, and c-Fos protein levels in the contralateral compared to the ipsilateral hemisphere; however, the increase in CGG KI mice was less than wildtype mice. Increases in Fmrp and Arc proteins scaled with learning, whereas this relationship was not observed with the c-Fos levels. These data suggest the possibility that reduced levels of activity-dependent proteins associated with synaptic plasticity such as Fmrp and Arc may contribute to the neurocognitive phenotype reported in the CGG KI mice and the fragile X premutation.

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Keywords Arc, C-Fos, CGG KI mouse, Endophenotype, Fmrp, Fragile X premutation, Western blot
Persistent URL dx.doi.org/10.1016/j.nlm.2014.01.011, hdl.handle.net/1765/76394
Journal Neurobiology of Learning and Memory
Citation
von Leden, R.E, Curley, L.C, Greenberg, G.D, Hunsaker, M.R, Willemsen, R, & Berman, R.F. (2014). Reduced activity-dependent protein levels in a mouse model of the fragile X premutation. Neurobiology of Learning and Memory, 109, 160–168. doi:10.1016/j.nlm.2014.01.011