A gene expression program activated by neuronal inactivity

Long term synaptic plasticity requires transcriptional changes in response to neuronal activity. While neuronal activity rapidly increases transcription of activity-regulated genes, it is less clear how neurons respond to neuronal inactivity. The plasticity gene Pura encodes a Rho1 GEF whose rhythmic expression drives 24 hour rhythms in the retraction of the projections of Drosophila LNv circadian pacemaker neurons. We found that Pura transcription in LNvs is repressed by neuronal activity and induced by neuronal inactivity - the opposite of canonical activity-regulated genes. We identified the Pax6 transcription factor Toy as the relevant activator of Pura transcription, and found that toy transcription itself is induced by neuronal inactivity and by reducing intracellular calcium. Thus we propose that neurons contain complementary gene expression programs that are activated by either increased or decreased neuronal activity.