Soma to neuron communication links stress adaptation to stress avoidance behavior

In multicellular organisms, signaling from the nervous system to the peripheral tissues can activate physiological responses to stress. Here, we show that inter-tissue stress communication can also function in reverse, i.e. from the peripheral tissue to the nervous system. osm-8 mutants, which activate the physiological osmotic stress response in the C. elegans skin, also exhibit defective osmotic avoidance (Osm) behavior, via a direct and specific effect on ASH osmosensory neuron excitability. Both osm-8 and the Patched-related gene ptr-23 , mutations in which suppress all osm-8 phenotypes, function in the hypodermal lysosomes to regulate both physiology and behavior. Unbiased lipidomics shows that osm-8 leads to a ptr-23 -dependent elevation of the lysosome specific lipid bis(monoacylglycero)phosphate (BMP) and expansion of the pool of hypodermal lysosomes. Just as genetic activation of the osmotic stress response by loss of osm-8 in the hypodermis causes an Osm phenotype, acute physiological exposure to osmotic stress also confers a reversible Osm phenotype. Behavioral and genetic plasticity requires biosynthesis of the compatible solute glycerol, a key physiological output of the organismal osmotic stress response. However, ptr-23 is only required for osm-8 induced behavioral plasticity and not physiological plasticity. Instead, both genetic and physiologically induced Osm phenotypes require the unusual non-neuronal lysosomal V-ATPase subunit vha-5 , which is also critical for organismal osmotic stress survival. Together, these data reveal that genetic or physiological activation of stress signaling from the skin elicits lysosome-associated signals that modulate organismal neurophysiology to attenuate a sensory neuron circuit. Such ‘body-brain’ interoceptive communication may allow organisms to better match neuronal decision-making with organismal physiological state.