Modulation by NPY/NPF-like receptor underlies experience-dependent, sexually dimorphic learning

Sonu Peedikayil-Kurien, Rizwanul Haque, Asaf Gat and Meital Oren-Suissa ()
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Sonu Peedikayil-Kurien: Weizmann Institute of Science
Rizwanul Haque: Weizmann Institute of Science
Asaf Gat: Weizmann Institute of Science
Meital Oren-Suissa: Weizmann Institute of Science

Nature Communications, 2025, vol. 16, issue 1, 1-16

Abstract: Abstract The evolutionary paths taken by each sex within a given species sometimes diverge, resulting in behavioral differences. Given their distinct needs, the mechanism by which each sex learns from a shared experience is still an open question. Here, we reveal sexual dimorphism in learning: C. elegans males do not learn to avoid the pathogenic bacteria PA14 as efficiently and rapidly as hermaphrodites. Notably, neuronal activity following pathogen exposure was dimorphic: hermaphrodites generate robust representations, while males, in line with their behavior, exhibit contrasting representations. Transcriptomic and behavioral analysis revealed that the neuropeptide receptor npr-5, an ortholog of the mammalian NPY/NPF-like receptor, regulates male learning by modulating neuronal activity. Furthermore, we show the dependency of the males’ decision-making on their sexual status and demonstrate the role of npr-5 as a modulator of incoming sensory cues. Taken together, these findings illustrate how neuromodulators drive sex-specific behavioral plasticity in response to a shared experience.

Date: 2025
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DOI: 10.1038/s41467-025-55950-7

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