Neuron
Volume 105, Issue 6, 18 March 2020, Pages 1094-1111.e10
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Article
Estimation of Current and Future Physiological States in Insular Cortex

https://doi.org/10.1016/j.neuron.2019.12.027Get rights and content
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Highlights

  • InsCtx ongoing activity patterns reflect current bodily state, not behavioral state

  • Hypothalamic hunger/thirst neurons gate InsCtx responses to food/water cues

  • Hypothalamic hunger/thirst neurons do not gate InsCtx ongoing activity

  • Food/water cues drive transient “simulations” of future bodily states in InsCtx

Summary

Interoception, the sense of internal bodily signals, is essential for physiological homeostasis, cognition, and emotions. While human insular cortex (InsCtx) is implicated in interoception, the cellular and circuit mechanisms remain unclear. We imaged mouse InsCtx neurons during two physiological deficiency states: hunger and thirst. InsCtx ongoing activity patterns reliably tracked the gradual return to homeostasis but not changes in behavior. Accordingly, while artificial induction of hunger or thirst in sated mice via activation of specific hypothalamic neurons (AgRP or SFOGLUT) restored cue-evoked food- or water-seeking, InsCtx ongoing activity continued to reflect physiological satiety. During natural hunger or thirst, food or water cues rapidly and transiently shifted InsCtx population activity to the future satiety-related pattern. During artificial hunger or thirst, food or water cues further shifted activity beyond the current satiety-related pattern. Together with circuit-mapping experiments, these findings suggest that InsCtx integrates visceral-sensory signals of current physiological state with hypothalamus-gated amygdala inputs that signal upcoming ingestion of food or water to compute a prediction of future physiological state.

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