The activity of neuronal circuits depends on the properties of the constituent neurons and their underlying synaptic and intrinsic currents. We describe the effects of extreme changes in extracellular pH – from pH 5.5 to 10.4 – on two central pattern generating networks, the stomatogastric and cardiac ganglia of the crab, Cancer borealis. Given that the physiological properties of ion channels are known to be sensitive to pH within the range tested, it is surprising that these rhythms generally remained robust from pH 6.1 to pH 8.8. The pH sensitivity of these rhythms was highly variable between animals and, unexpectedly, between ganglia. Animal-to-animal variability was likely a consequence of similar network performance arising from variable sets of underlying conductances. Together, these results illustrate the potential difficulty in generalizing the effects of environmental perturbation across circuits, even within the same animal.

Animals integrate changes in external and internal environments to generate behavior. While neural circuits detecting external cues have been mapped, less is known about how internal states like hunger are integrated into behavioral outputs. Here, we use the nematode C. elegans to examine how changes in internal nutritional status affect chemosensory behaviors. We show that acute food deprivation leads to a reversible decline in repellent, but not attractant, sensitivity. This behavioral change requires two conserved transcription factors MML-1 (MondoA) and HLH-30 (TFEB), both of which translocate from the intestinal nuclei to the cytoplasm during food deprivation. Next, we identify the insulin-like peptide INS-31 as a candidate ligand relaying food-status signals from the intestine to other tissues. Further, we show that neurons likely use the DAF-2 insulin receptor and AGE-1/PI-3 Kinase, but not DAF-16/FOXO to integrate these intestine-released peptides. Altogether, our study shows how internal food status signals are integrated by transcription factors and intestine-neuron signaling to generate flexible behaviors via the gut-brain axis.

Animals and their neuronal circuits must maintain function despite significant environmental fluctuations. The crab, Cancer borealis, experiences daily changes in ocean temperature and pH. Here, we describe the effects of extreme changes in extracellular pH -from pH 5.5 to 10.4 -on two central pattern generating networks, the stomatogastric and cardiac ganglia of C. borealis. Given that the physiological properties of ion channels are known to be sensitive to pH within the range tested, it is surprising that these rhythms generally remained robust from pH 6.1 to pH 8.8. Unexpectedly, the stomatogastric ganglion was more sensitive to acid while the cardiac ganglion was more sensitive to base. Considerable animal-to-animal variability was likely a consequence of similar network performance arising from variable sets of underlying conductances.Together, these results illustrate the potential difficulty in generalizing the effects of environmental perturbation across circuits, even within the same animal.

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