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Deconstruction of a neural circuit for hunger

Author

Listed:
  • Deniz Atasoy

    (Janelia Farm Research Campus, Howard Hughes Medical Institute)

  • J. Nicholas Betley

    (Janelia Farm Research Campus, Howard Hughes Medical Institute)

  • Helen H. Su

    (Janelia Farm Research Campus, Howard Hughes Medical Institute)

  • Scott M. Sternson

    (Janelia Farm Research Campus, Howard Hughes Medical Institute)

Abstract

Hunger is a complex behavioural state that elicits intense food seeking and consumption. These behaviours are rapidly recapitulated by activation of starvation-sensitive AGRP neurons, which present an entry point for reverse-engineering neural circuits for hunger. Here we mapped synaptic interactions of AGRP neurons with multiple cell populations in mice and probed the contribution of these distinct circuits to feeding behaviour using optogenetic and pharmacogenetic techniques. An inhibitory circuit with paraventricular hypothalamus (PVH) neurons substantially accounted for acute AGRP neuron-evoked eating, whereas two other prominent circuits were insufficient. Within the PVH, we found that AGRP neurons target and inhibit oxytocin neurons, a small population that is selectively lost in Prader–Willi syndrome, a condition involving insatiable hunger. By developing strategies for evaluating molecularly defined circuits, we show that AGRP neuron suppression of oxytocin neurons is critical for evoked feeding. These experiments reveal a new neural circuit that regulates hunger state and pathways associated with overeating disorders.

Suggested Citation

  • Deniz Atasoy & J. Nicholas Betley & Helen H. Su & Scott M. Sternson, 2012. "Deconstruction of a neural circuit for hunger," Nature, Nature, vol. 488(7410), pages 172-177, August.
  • Handle: RePEc:nat:nature:v:488:y:2012:i:7410:d:10.1038_nature11270
    DOI: 10.1038/nature11270
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    Cited by:

    1. Shaowen Qian & Sumei Yan & Ruiqi Pang & Jing Zhang & Kai Liu & Zhiyue Shi & Zhaoqun Wang & Penghui Chen & Yanjie Zhang & Tiantian Luo & Xianli Hu & Ying Xiong & Yi Zhou, 2022. "A temperature-regulated circuit for feeding behavior," Nature Communications, Nature, vol. 13(1), pages 1-17, December.
    2. Aki Takahashi & Romain Durand-de Cuttoli & Meghan E. Flanigan & Emi Hasegawa & Tomomi Tsunematsu & Hossein Aleyasin & Yoan Cherasse & Ken Miya & Takuya Okada & Kazuko Keino-Masu & Koshiro Mitsui & Lon, 2022. "Lateral habenula glutamatergic neurons projecting to the dorsal raphe nucleus promote aggressive arousal in mice," Nature Communications, Nature, vol. 13(1), pages 1-18, December.
    3. Takashi Nagashima & Suguru Tohyama & Kaori Mikami & Masashi Nagase & Mieko Morishima & Atsushi Kasai & Hitoshi Hashimoto & Ayako M. Watabe, 2022. "Parabrachial-to-parasubthalamic nucleus pathway mediates fear-induced suppression of feeding in male mice," Nature Communications, Nature, vol. 13(1), pages 1-17, December.
    4. Taku Hasegawa & Satomi Chiken & Kenta Kobayashi & Atsushi Nambu, 2022. "Subthalamic nucleus stabilizes movements by reducing neural spike variability in monkey basal ganglia," Nature Communications, Nature, vol. 13(1), pages 1-15, December.
    5. Mingming Xing & Yang Li & Yuqi Zhang & Juemou Zhou & Danting Ma & Mengqi Zhang & Minglei Tang & Ting Ouyang & Fumiao Zhang & Xiaofeng Shi & Jianyuan Sun & Zuxin Chen & Weiping J. Zhang & Shuli Zhang &, 2024. "Paraventricular hypothalamic RUVBL2 neurons suppress appetite by enhancing excitatory synaptic transmission in distinct neurocircuits," Nature Communications, Nature, vol. 15(1), pages 1-21, December.
    6. Roberto Luca & Stefano Nardone & Kevin P. Grace & Anne Venner & Michela Cristofolini & Sathyajit S. Bandaru & Lauren T. Sohn & Dong Kong & Takatoshi Mochizuki & Bianca Viberti & Lin Zhu & Antonino Zit, 2022. "Orexin neurons inhibit sleep to promote arousal," Nature Communications, Nature, vol. 13(1), pages 1-15, December.
    7. Stephan Dodt & Noah V. Widdershooven & Marie-Luise Dreisow & Lisa Weiher & Lukas Steuernagel & F. Thomas Wunderlich & Jens C. Brüning & Henning Fenselau, 2024. "NPY-mediated synaptic plasticity in the extended amygdala prioritizes feeding during starvation," Nature Communications, Nature, vol. 15(1), pages 1-16, December.

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