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

Area of Science:

• Neuroscience
• Genetics
• Molecular Biology

Background:

• The insulin/insulin-like signaling (IIS) pathway is crucial for adult functions in *C. elegans*, including learning and memory.
• Previous transcriptomic analyses lacked the resolution to identify neuron-specific changes in IIS pathway mutants like *daf-2*.

Approach:

• Utilized single-nucleus RNA sequencing to profile transcriptomes of individual neuron types in adult wild-type and *daf-2* mutant *C. elegans*.
• Compared Day 1 adult neuron transcriptomes with L4 larval stages to identify developmental and mutation-specific changes.
• Integrated transcriptomic data with behavioral assays and genetic manipulation to validate findings.

Key Points:

• Identified significant differences in chemoreceptor, synaptic, and learning/memory gene expression between larval and adult neurons.
• Discovered adult AWC neuron-specific regulators of chemosensory function and predicted neuron-to-neuron peptide/receptor interactions.
• Found gene expression changes in *daf-2* mutants, particularly in the AWC neuron, correlating with enhanced learning and memory.

Conclusions:

• Single-nucleus sequencing provides high-resolution insights into neuron-specific transcriptomic alterations.
• Identified conserved genes functioning in single neurons that regulate behavior, including learning and memory.
• The *daf-2* mutation confers neuron-specific improvements in cognitive functions through transcriptional regulation.