IDEAS home Printed from https://ideas.repec.org/a/nat/natcom/v16y2025i1d10.1038_s41467-025-59686-2.html
   My bibliography  Save this article

Energy state guides reward seeking via an extended amygdala to lateral hypothalamus pathway

Author

Listed:
  • Kuldeep Shrivastava

    (Rutgers Robert Wood Johnson Medical School)

  • Vikshar Athreya

    (Rutgers Robert Wood Johnson Medical School)

  • Yi Lu

    (Rutgers Robert Wood Johnson Medical School)

  • Jorge Luis-Islas

    (Rutgers Robert Wood Johnson Medical School)

  • Ashley Han

    (Rutgers Robert Wood Johnson Medical School)

  • Tess F. Kowalski

    (Rutgers Robert Wood Johnson Medical School)

  • Mark A. Rossi

    (Rutgers Robert Wood Johnson Medical School
    Rutgers Robert Wood Johnson Medical School
    Rutgers Robert Wood Johnson Medical School
    Rutgers University)

Abstract

Impaired regulation of food intake underlies numerous health problems, including obesity and type 2 diabetes, yet how brain systems controlling reward seeking become dysregulated to promote overeating is unknown. Glutamatergic neurons of the lateral hypothalamic area (LHA) are thought to act as a brake on feeding, which is dysregulated during diet-induced obesity. These neurons receive input from the extended amygdala, including the bed nucleus of the stria terminalis (BNST). However, the circuit mechanisms underlying the ability of this pathway to control feeding behavior and how they contribute to dysregulated eating are unclear. Here, we discover that BNST projections to LHA (BNST→LHA) promote reward seeking in an energy state-dependent manner by combining optogenetics, in vivo multiphoton calcium imaging, and electrophysiology in mice. Synaptic strength and neuronal function within the BNST→LHA pathway are dynamically regulated according to energy state to guide reward seeking. These findings suggest that hormonal factors modulate the function of the BNST→LHA pathway to align food seeking with current energy needs.

Suggested Citation

  • Kuldeep Shrivastava & Vikshar Athreya & Yi Lu & Jorge Luis-Islas & Ashley Han & Tess F. Kowalski & Mark A. Rossi, 2025. "Energy state guides reward seeking via an extended amygdala to lateral hypothalamus pathway," Nature Communications, Nature, vol. 16(1), pages 1-16, December.
  • Handle: RePEc:nat:natcom:v:16:y:2025:i:1:d:10.1038_s41467-025-59686-2
    DOI: 10.1038/s41467-025-59686-2
    as

    Download full text from publisher

    File URL: https://www.nature.com/articles/s41467-025-59686-2
    File Function: Abstract
    Download Restriction: no

    File URL: https://libkey.io/10.1038/s41467-025-59686-2?utm_source=ideas
    LibKey link: if access is restricted and if your library uses this service, LibKey will redirect you to where you can use your library subscription to access this item
    ---><---

    References listed on IDEAS

    as
    1. Sung-Yon Kim & Avishek Adhikari & Soo Yeun Lee & James H. Marshel & Christina K. Kim & Caitlin S. Mallory & Maisie Lo & Sally Pak & Joanna Mattis & Byung Kook Lim & Robert C. Malenka & Melissa R. Ward, 2013. "Diverging neural pathways assemble a behavioural state from separable features in anxiety," Nature, Nature, vol. 496(7444), pages 219-223, April.
    2. Ou Fu & Yuu Iwai & Masataka Narukawa & Ayako W. Ishikawa & Kentaro K. Ishii & Ken Murata & Yumiko Yoshimura & Kazushige Touhara & Takumi Misaka & Yasuhiko Minokoshi & Ken-ichiro Nakajima, 2019. "Hypothalamic neuronal circuits regulating hunger-induced taste modification," Nature Communications, Nature, vol. 10(1), pages 1-14, December.
    3. Joshua H. Jennings & Dennis R. Sparta & Alice M. Stamatakis & Randall L. Ung & Kristen E. Pleil & Thomas L. Kash & Garret D. Stuber, 2013. "Distinct extended amygdala circuits for divergent motivational states," Nature, Nature, vol. 496(7444), pages 224-228, April.
    4. Yong Wang & JungMin Kim & Matthew B. Schmit & Tiffany S. Cho & Caohui Fang & Haijiang Cai, 2019. "A bed nucleus of stria terminalis microcircuit regulating inflammation-associated modulation of feeding," Nature Communications, Nature, vol. 10(1), pages 1-13, December.
    5. Huan Sheng & Chao Lei & Yu Yuan & Yali Fu & Dongyang Cui & Li Yang & Da Shao & Zixuan Cao & Hao Yang & Xinli Guo & Chenshan Chu & Yaxian Wen & Zhangyin Cai & Ming Chen & Bin Lai & Ping Zheng, 2023. "Nucleus accumbens circuit disinhibits lateral hypothalamus glutamatergic neurons contributing to morphine withdrawal memory in male mice," Nature Communications, Nature, vol. 14(1), pages 1-16, December.
    6. Young Hee Lee & Yu-Been Kim & Kyu Sik Kim & Mirae Jang & Ha Young Song & Sang-Ho Jung & Dong-Soo Ha & Joon Seok Park & Jaegeon Lee & Kyung Min Kim & Deok-Hyeon Cheon & Inhyeok Baek & Min-Gi Shin & Eun, 2023. "Lateral hypothalamic leptin receptor neurons drive hunger-gated food-seeking and consummatory behaviours in male mice," Nature Communications, Nature, vol. 14(1), pages 1-16, December.
    Full references (including those not matched with items on IDEAS)

    Most related items

    These are the items that most often cite the same works as this one and are cited by the same works as this one.
    1. Anna J. Bowen & Y. Waterlily Huang & Jane Y. Chen & Jordan L. Pauli & Carlos A. Campos & Richard D. Palmiter, 2023. "Topographic representation of current and future threats in the mouse nociceptive amygdala," Nature Communications, Nature, vol. 14(1), pages 1-16, December.
    2. Young Hee Lee & Yu-Been Kim & Kyu Sik Kim & Mirae Jang & Ha Young Song & Sang-Ho Jung & Dong-Soo Ha & Joon Seok Park & Jaegeon Lee & Kyung Min Kim & Deok-Hyeon Cheon & Inhyeok Baek & Min-Gi Shin & Eun, 2023. "Lateral hypothalamic leptin receptor neurons drive hunger-gated food-seeking and consummatory behaviours in male mice," Nature Communications, Nature, vol. 14(1), pages 1-16, December.
    3. 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.
    4. Ren-Wen Han & Zi-Yi Zhang & Chen Jiao & Ze-Yu Hu & Bing-Xing Pan, 2024. "Synergism between two BLA-to-BNST pathways for appropriate expression of anxiety-like behaviors in male mice," Nature Communications, Nature, vol. 15(1), pages 1-18, December.
    5. Robert N. Fetcho & Baila S. Hall & David J. Estrin & Alexander P. Walsh & Peter J. Schuette & Jesse Kaminsky & Ashna Singh & Jacob Roshgodal & Charlotte C. Bavley & Viraj Nadkarni & Susan Antigua & Th, 2023. "Regulation of social interaction in mice by a frontostriatal circuit modulated by established hierarchical relationships," Nature Communications, Nature, vol. 14(1), pages 1-15, December.
    6. Jing-Jing Yan & Xiao-Jing Ding & Ting He & Ai-Xiao Chen & Wen Zhang & Zi-Xian Yu & Xin-Yu Cheng & Chuan-Yao Wei & Qiao-Dan Hu & Xiao-Yao Liu & Yan-Li Zhang & Mengge He & Zhi-Yong Xie & Xi Zha & Chun X, 2022. "A circuit from the ventral subiculum to anterior hypothalamic nucleus GABAergic neurons essential for anxiety-like behavioral avoidance," Nature Communications, Nature, vol. 13(1), pages 1-16, December.
    7. Lingli Luo & Wei Jing & Yiqing Guo & Dan Liu & Aodi He & Youming Lu, 2025. "A cell-type-specific circuit of somatostatin neurons in the habenula encodes antidepressant action in male mice," Nature Communications, Nature, vol. 16(1), pages 1-19, December.
    8. 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.
    9. Li Shen & Guang-Wei Zhang & Can Tao & Michelle B. Seo & Nicole K. Zhang & Junxiang J. Huang & Li I. Zhang & Huizhong W. Tao, 2022. "A bottom-up reward pathway mediated by somatostatin neurons in the medial septum complex underlying appetitive learning," Nature Communications, Nature, vol. 13(1), pages 1-15, December.
    10. Lihong Yan & Xin Zhang & Liling Jin & Yin Li & Yang Chen & Jubiao Zhang & Zhenning Sun & Junxia Qi & Changqing Qu & Guanzhong Dong & Yongjie Zhang & Qin Jiang & An Liu & Juxue Li, 2025. "The ARCCRABP1 neurons play a crucial role in the regulation of energy homeostasis," Nature Communications, Nature, vol. 16(1), pages 1-16, December.
    11. 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.

    More about this item

    Statistics

    Access and download statistics

    Corrections

    All material on this site has been provided by the respective publishers and authors. You can help correct errors and omissions. When requesting a correction, please mention this item's handle: RePEc:nat:natcom:v:16:y:2025:i:1:d:10.1038_s41467-025-59686-2. See general information about how to correct material in RePEc.

    If you have authored this item and are not yet registered with RePEc, we encourage you to do it here. This allows to link your profile to this item. It also allows you to accept potential citations to this item that we are uncertain about.

    If CitEc recognized a bibliographic reference but did not link an item in RePEc to it, you can help with this form .

    If you know of missing items citing this one, you can help us creating those links by adding the relevant references in the same way as above, for each refering item. If you are a registered author of this item, you may also want to check the "citations" tab in your RePEc Author Service profile, as there may be some citations waiting for confirmation.

    For technical questions regarding this item, or to correct its authors, title, abstract, bibliographic or download information, contact: Sonal Shukla or Springer Nature Abstracting and Indexing (email available below). General contact details of provider: http://www.nature.com .

    Please note that corrections may take a couple of weeks to filter through the various RePEc services.

    IDEAS is a RePEc service. RePEc uses bibliographic data supplied by the respective publishers.