SRP174417 PRJNA511677 GSE124343 Differential regulation of gene expression in neurons by spontaneous or sensory-driven activity and its dysregulation with aging We identify a network of genes that change immediately after odor and light exposure in peripheral and central nervous system tissues in the model Drosophila melanogaster. We demonstrate in the antenna, that this regulation is dependent on olfactory signaling. This study provides several intriguing candidate genes that have potential for involvement in synaptic plasticity and learning and memory. We find that regulation of these genes is disrupted in ageing flies that are memory compromised. This provides a framework to both characterize this important class of genes and understand how their regulation contributes to the molecular mechanisms behind declining memory. Furthermore, many of our strongest candidates could prove to be valuable tools for neuronal circuit tracing in this amenable genetic model system. Overall design: Drosophila antenna: RNA-Seq profiles were generated with the Illumina NextSeq500 platform with biological replicates. Odor and light-treated antennal samples (stim) were compared to control antennal samples from flies that remained sensory deprived (0min). Drosophila brain time-series: RNA-Seq profiles were generated with the Illumina HiSeq2000 and NextSeq500 platforms with 3 biological replicates. Odor and light-stimulated brains were compared to samples from flies that remained sensory deprived (0min). Drosophila brain aging: RNA-Seq profiles were generated with the Illumina HiSeq2000 and NextSeq500 platforms with biological replicates. Odor and light-stimulated brains (stim) were compared to samples from flies that remained sensory deprived (0min) for 10- and 25-day old flies. Drosophila HDAC6 mutant brains: RNA-Seq profiles were generated with the Illumina NextSeq500 platform with biological replicates. Odor and light-treated brain samples (stim) were compared to control samples form flies that remained sensory deprived. GSE124343