A rapid and dynamic role for FMRP in the plasticity of adult neurons.

Fragile X syndrome (FXS) is a neuro-developmental disorder caused by silencing , which encodes the RNA-binding protein FMRP. Although is expressed in adult neurons, it has been challenging to separate acute from chronic effects of loss of in models of FXS. We have used the precision of genetics to test if acutely affects adult neuronal plasticity , focusing on the s-LNv circadian pacemaker neurons that show 24 hour rhythms in structural plasticity. We found that over-expressing for only 4 hours blocks the activity-dependent expansion of s-LNv projections without altering the circadian clock or activity-regulated gene expression. Conversely, acutely reducing expression prevented s-LNv projections from retracting. One FMRP target that we identified in s-LNvs is , which encodes a Rac1 GEF. Our data indicate that FMRP normally reduces mRNA translation at dusk to reduce Rac1 activity. Overall, our data reveal a previously unappreciated rapid and direct role for FMRP in acutely regulating neuronal plasticity in adult neurons, and underscore the importance of RNA-binding proteins in this process.