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

Fragile X syndrome is a neurodevelopmental disorder caused by silencing Fragile X messenger ribonucleoprotein 1 (Fmr1), which encodes the FMRP RNA-binding protein. Although Fmr1 is expressed in adult neurons, it has been challenging to separate acute from chronic effects of loss of Fmr1. Here we use the precision of Drosophila genetics to show that FMRP acutely regulates neuronal plasticity in adult small ventral lateral circadian pacemaker neurons (s-LNvs), which show daily rhythms in their structure. We find that Fmr1 is required for structural plasticity in s-LNvs, and that reducing Fmr1 expression for only 4 hours prevented s-LNv projections from retracting. Conversely, briefly overexpressing Fmr1 blocks the activity-dependent expansion of s-LNv projections without major changes to the circadian clock or to activity-regulated gene expression. One FMRP target we identify in s-LNvs is sif, which encodes a Rac1 Guanine nucleotide exchange factor. Our data suggest that FMRP normally reduces sif mRNA translation at dusk to reduce Rac1 activity and regulate adult neuronal plasticity.