An enteric neuron ionotropic receptor regulates salt stress resistance

. Here we show that the I3 pharyngeal enteric neuron responds to cations via an I3-specific ionotropic receptor to regulate salt stress tolerance. The GLR-9 ionotropic receptor and the GLR-7 IR25a co-receptor orthologue localize to the gut lumen-exposed sensory ending of I3, and are necessary and sufficient for salt sensation. Salt detection by I3 protects specifically against high-salt stress, as glr-9 mutants show reduced tolerance of hypertonic salt but not of sugar solutions, with or without prior acclimatization. Whereas cholinergic signalling from I3 promotes tolerance of acute high-salt stress, peptidergic signalling from I3 during acclimatization is essential for resistance to a subsequent high-salt challenge. Transcriptomic and reporter gene analyses show that I3 modulates salt tolerance in part by regulating the expression of salt stress response genes in distal tissues. Correspondingly, mutations in a subset of salt- and GLR-9-regulated genes reduce salt stress resistance. Our results describe the mechanisms by which chemosensation mediated by a defined enteric neuron regulates physiological homeostasis in response to a specific abiotic stress.