Adult single-nucleus neuronal transcriptomes of insulin signaling mutants reveal regulators of behavior and learning

Gene expression in individual neurons can change during development to adulthood and can have large effects on behavior. Additionally, the insulin/insulin-like signaling (IIS) pathway regulates many of the adult functions of Caenorhabditis elegans, including learning and memory, via transcriptional changes. We used the deep resolution of single-nucleus RNA sequencing to define the adult transcriptome of each neuron in wild-type and daf-2 mutants, revealing expression differences between L4 larval and adult neurons in chemoreceptors, synaptic genes, and learning/memory genes. We used these data to identify adult new AWC-specific regulators of chemosensory function that emerge upon adulthood. daf-2 gene expression changes correlate with improved cognitive functions, particularly in the AWC sensory neuron that controls learning and associative memory; behavioral assays of AWC-specific daf-2 genes revealed their roles in cognitive function. Combining technology and functional validation, we identified conserved genes that function in specific adult neurons to control behavior, including learning and memory.