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bioRxiv · 10.1101/2024.02.07.579364

Adult Single-nucleus Neuronal Transcriptomes of Insulin Signaling Mutants Reveal Regulators of Behavior and Learning

St. Ange, J.·Weng, Y.·Stevenson, M.·Kaletsky, R.·Moore, R. S.·Zhou, S.·Murphy, C.
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Abstract

The insulin/insulin-like signaling (IIS) pathway regulates many of C. elegans adult functions, including learning and memory1. While whole-worm and tissue-specific transcriptomic analyses have identified IIS targets2,3, a higher-resolution single-cell approach is required to identify changes that confer neuron-specific improvements in the long-lived insulin receptor mutant, daf-2. To understand how behaviors that are controlled by a small number of neurons change in daf-2 mutants, we used the deep resolution of single-nucleus RNA sequencing to define each neuron types transcriptome in adult wild-type and daf-2 mutants. First, we found surprising differences between wild-type L4 larval neurons and young adult neurons in chemoreceptor expression, synaptic genes, and learning and memory genes. These Day 1 adult neuron transcriptomes allowed us to identify adult AWC-specific regulators of chemosensory function and to predict neuron-to-neuron peptide/receptor pairs. We then identified gene expression changes that correlate with daf-2s improved cognitive functions, particularly in the AWC sensory neuron that controls learning and associative memory4, and used behavioral assays to test their roles in cognitive function. Combining deep single-neuron transcriptomics, genetic manipulation, and behavioral analyses enabled us to identify genes that may function in a single adult neuron to control behavior, including conserved genes that function in learning and memory. One-Sentence SummarySingle-nucleus sequencing of adult wild-type and daf-2 C. elegans neurons reveals functionally relevant transcriptional changes, including regulators of chemosensation, learning, and memory.

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St. Ange, J., Weng, Y., Stevenson, M., Kaletsky, R., Moore, R. S., Zhou, S., Murphy, C.. 2024-02-07. Adult Single-nucleus Neuronal Transcriptomes of Insulin Signaling Mutants Reveal Regulators of Behavior and Learning. https://doi.org/10.1101/2024.02.07.579364

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