GEOapplication/xmlftp://ftp.ncbi.nlm.nih.gov/geo/series/GSE295nnn/GSE295724/primaryOK200GenomicsDanio rerioGenome binding/occupancy profiling by high throughput sequencing Expression profiling by high throughput sequencinghttps://www.ncbi.nlm.nih.gov/geo/query/acc.cgi?acc=GSE295724GEOGSEfalseNeuronal microexons modulate arousal via the cAMP-PKA-CREB pathway in zebrafishProper regulation of arousal maintains the balance of rest and activity and enables appropriate responses to stimuli; its disruption is a hallmark of many neurodevelopmental disorders. While transcriptional mechanisms of arousal control are well-defined, the contribution of post-transcriptional processes such as alternative splicing remains unclear. Here, we identify a critical role for the microexon splicing regulator srrm3 in maintaining arousal homeostasis in zebrafish. srrm3 mutants exhibit persistent hyperarousal characterized by sleep loss, sensory hypersensitivity, and elevated behavioural and neuronal activity. We identify the cAMP-PKA-CREB signaling axis as a central driver of mutant hyperarousal. Specifically, pharmacological inhibition of cAMP signalling rescues mutant hyperactivity and associated transcriptional changes while wild-type cAMP activation phenocopies the mutant. Downregulation of immediate early genes and a reduced CREB phosphorylation further suggest adaptation to sustained neuronal activation. These findings establish srrm3-dependent microexon splicing as a key molecular layer of arousal regulation linking RNA-processing defects to neuromodulatory imbalance.2026/04/24GSE295724GSM8956034GSM8956035GSM8956032GSM8956033GSM8956030GSM8956031GSM9345110GSM8956038GSM9345111GSM8956039GSM8956036GSM9345112GSM8956037GSM8956023GSM8956067GSM8956068GSM8956024GSM8956021GSM8956065GSM8956066GSM8956022GSM8956063GSM8956020GSM8956064GSM8956061GSM8956062GSM8956060GSM8956029GSM8956027GSM8956028GSM8956025GSM8956069GSM8956026GSM8956056GSM8956057GSM8956054GSM8956055GSM8956052GSM8956053GSM8956050GSM8956051GSM8956018GSM8956019GSM8956017GSM8956058GSM8956059GSM8956045GSM8956046GSM8956043GSM8956044GSM8956041GSM8956042GSM8956040GSM9345107GSM9345108GSM9345109GSM8956049GSM8956047GSM895604818413208283061424995295724Danio rerio