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Food cue regulation of AGRP hunger neurons guides learning

Author

Listed:
  • Janet Berrios

    (Harvard Medical School)

  • Chia Li

    (National Institutes of Health
    National Institutes of Health)

  • Joseph C. Madara

    (Harvard Medical School)

  • Alastair S. Garfield

    (Harvard Medical School
    Rhythm Pharmaceuticals)

  • Jennifer S. Steger

    (Harvard Medical School
    Nanodropper)

  • Michael J. Krashes

    (National Institutes of Health
    National Institutes of Health)

  • Bradford B. Lowell

    (Harvard Medical School
    Harvard Medical School)

Abstract

Agouti-related peptide (AGRP)-expressing neurons are activated by fasting—this causes hunger1–4, an aversive state that motivates the seeking and consumption of food5,6. Eating returns AGRP neuron activity towards baseline on three distinct timescales: rapidly and transiently following sensory detection of food cues6–8, slowly and longer-lasting in response to nutrients in the gut9,10, and even more slowly and permanently with restoration of energy balance9,11. The rapid regulation by food cues is of particular interest as its neurobiological basis and purpose are unknown. Given that AGRP neuron activity is aversive6, the sensory cue-linked reductions in activity could function to guide behaviour. To evaluate this, we first identified the circuit mediating sensory cue inhibition and then selectively perturbed it to determine function. Here, we show that a lateral hypothalamic glutamatergic → dorsomedial hypothalamic GABAergic (γ-aminobutyric acid-producing)12 → AGRP neuron circuit mediates this regulation. Interference with this circuit impairs food cue inhibition of AGRP neurons and, notably, greatly impairs learning of a sensory cue-initiated food-acquisition task. This is specific for food, as learning of an identical water-acquisition task is unaffected. We propose that decreases in aversive AGRP neuron activity6 mediated by this food-specific circuit increases the incentive salience13 of food cues, and thus facilitates the learning of food-acquisition tasks.

Suggested Citation

  • Janet Berrios & Chia Li & Joseph C. Madara & Alastair S. Garfield & Jennifer S. Steger & Michael J. Krashes & Bradford B. Lowell, 2021. "Food cue regulation of AGRP hunger neurons guides learning," Nature, Nature, vol. 595(7869), pages 695-700, July.
  • Handle: RePEc:nat:nature:v:595:y:2021:i:7869:d:10.1038_s41586-021-03729-3
    DOI: 10.1038/s41586-021-03729-3
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    Cited by:

    1. Predrag Jovanovic & Allan-Hermann Pool & Nancy Morones & Yidan Wang & Edward Novinbakht & Nareg Keshishian & Kaitlyn Jang & Yuki Oka & Celine E. Riera, 2023. "A sex-specific thermogenic neurocircuit induced by predator smell recruiting cholecystokinin neurons in the dorsomedial hypothalamus," Nature Communications, Nature, vol. 14(1), pages 1-19, December.
    2. Qin Wang & Rui-Yue Sun & Jia-Xue Hu & Yan-Hui Sun & Chun-Yue Li & Huiqian Huang & Hao Wang & Xiao-Ming Li, 2024. "Hypothalamic-hindbrain circuit for consumption-induced fear regulation," Nature Communications, Nature, vol. 15(1), pages 1-14, December.

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