Starvation transforms signal encoding in C. elegans thermoresponsive neurons and suppresses heat avoidance via bidirectional glutamatergic and peptidergic signaling

Animals must continuously adapt their behavioral outputs in response to changes in internal state, including nutritional state. Here, we show that starvation induces a profound and progressive suppression of thermonociceptive behavior in Caenorhabditis elegans. The thermoresponsive sensory neurons AWCs mediate robust heat-evoked reversals over a broad range of stimulus intensities via glutamate and FLP-6 neuropeptide signaling, each covering distinct heat intensity ranges. After six hours of food deprivation, heat-evoked reversal responses are nearly abolished, independently of any external food odor cues. Prolonged food deprivation triggers a switch in AWC heat-evoked activity patterns, transitioning from a predictable, stimulus-locked response mode to a heterogeneous and stochastic regime. This switch relies on ASI neurons, proposed to work as internal state-sensing neurons. INS-32 and NLP-18 neuropeptide signals from ASI switch from a reversal-promoting to a reversal-inhibiting effect. Glutamatergic transmission from non-AWC neurons is also engaged to suppress reversals. Our findings define a circuit logic by which nociceptive responsiveness gating by internal nutritional state is linked to dynamic modulation of sensory neuron activity patterns and orchestrated by bidirectional glutamatergic and neuropeptidergic signals. More broadly, this study illustrates how sensory systems integrate metabolic information to prioritize behavioral outputs under changing physiological conditions, providing mechanistic insight into the plastic coupling between sensation, internal state, and action selection.