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

Abstract

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. During early food deprivation (1 hr without food), the thermoresponsive AWC sensory neurons 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 6 hr of food deprivation (prolonged starvation), heat-evoked reversal responses are nearly abolished, independently of external food odor cues. Starvation shifts the distribution of AWC heat-evoked calcium response polarity, from mostly excitatory responses to a heterogeneous pattern combining excitatory and inhibitory activities. This switch relies on ASI neurons, proposed to sense internal state. INS-32 and NLP-18 neuropeptide signals from ASI switch from reversal-promoting to reversal-inhibiting effects. In addition, reversal-promoting glutamatergic transmission by AWC is antagonized by glutamatergic transmission from non-AWC neurons that suppress FLP-6-dependent reversals. Our findings define a circuit logic by which gating of nociceptive responsiveness by internal nutritional state is linked to dynamic modulation of sensory neuron activity patterns and orchestrated by bidirectional glutamatergic and neuropeptidergic signals.