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

Abstract

AbstractFragile X syndrome (FXS) is a neuro-developmental disorder caused by silencingFmr1, which encodes the RNA-binding protein FMRP. AlthoughFmr1is expressed in adult neurons, it has been challenging to separate acute from chronic effects of loss ofFmr1in models of FXS. We have used the precision ofDrosophilagenetics to test ifFmr1acutely affects adult neuronal plasticityin vivo, focusing on the s-LNv circadian pacemaker neurons that show 24 hour rhythms in structural plasticity. We found that over-expressingFmr1for only 4 hours blocks the activity-dependent expansion of s-LNv projections without altering the circadian clock or activity- regulated gene expression. Conversely, acutely reducingFmr1expression prevented s-LNv projections from retracting. One FMRP target that we identified in s-LNvs issif, which encodes a Rac1 GEF. Our data indicate that FMRP normally reducessifmRNA 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.