A distinct parabrachial-to-lateral hypothalamus circuit for motivational suppression of feeding by nociception

The motivation to eat is not only shaped by nutrition but also competed by external stimuli including pain. How the mouse hypothalamus, the feeding regulation center, integrates nociceptive inputs to modulate feeding is unclear. Within the key nociception relay center parabrachial nucleus (PBN), we...

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Main Authors: Phua, Siew Cheng, Tan, Yu Lin, Kok, Alison Maun Yeng, Senol, Esra, Chiam, Christine Jin Hui, Lee, Chun-Yao, Peng, Yanmin, Lim, Auriel Theodora Jacobea, Mohammad, Hasan, Lim, Jing-Xuan, Fu, Yu
Other Authors: Lee Kong Chian School of Medicine (LKCMedicine)
Format: Article
Language:English
Published: 2021
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Online Access:https://hdl.handle.net/10356/151045
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Institution: Nanyang Technological University
Language: English
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spelling sg-ntu-dr.10356-1510452023-03-05T16:44:54Z A distinct parabrachial-to-lateral hypothalamus circuit for motivational suppression of feeding by nociception Phua, Siew Cheng Tan, Yu Lin Kok, Alison Maun Yeng Senol, Esra Chiam, Christine Jin Hui Lee, Chun-Yao Peng, Yanmin Lim, Auriel Theodora Jacobea Mohammad, Hasan Lim, Jing-Xuan Fu, Yu Lee Kong Chian School of Medicine (LKCMedicine) Singapore Bioimaging Consortium, A*STAR Science::Medicine Brain Neurons The motivation to eat is not only shaped by nutrition but also competed by external stimuli including pain. How the mouse hypothalamus, the feeding regulation center, integrates nociceptive inputs to modulate feeding is unclear. Within the key nociception relay center parabrachial nucleus (PBN), we demonstrated that neurons projecting to the lateral hypothalamus (LHPBN) are nociceptive yet distinct from danger-encoding central amygdala–projecting (CeAPBN) neurons. Activation of LHPBN strongly suppressed feeding by limiting eating frequency and also reduced motivation to work for food reward. Refined approach-avoidance paradigm revealed that suppression of LHPBN, but not CeAPBN, sustained motivation to obtain food. The effect of LHPBN neurons on feeding was reversed by suppressing downstream LHVGluT2 neurons. Thus, distinct from a circuit for fear and escape responses, LHPBN neurons channel nociceptive signals to LHVGluT2 neurons to suppress motivational drive for feeding. Our study provides a new perspective in understanding feeding regulation by external competing stimuli. Agency for Science, Technology and Research (A*STAR) Published version This work was supported by an A*STAR Investigatorship provided by the Biomedical Research Council (BMRC) of A*STAR (1530700142 to Y.F.). 2021-06-25T06:39:34Z 2021-06-25T06:39:34Z 2021 Journal Article Phua, S. C., Tan, Y. L., Kok, A. M. Y., Senol, E., Chiam, C. J. H., Lee, C., Peng, Y., Lim, A. T. J., Mohammad, H., Lim, J. & Fu, Y. (2021). A distinct parabrachial-to-lateral hypothalamus circuit for motivational suppression of feeding by nociception. Science Advances, 7(19), eabe4323-. https://dx.doi.org/10.1126/sciadv.abe4323 2375-2548 https://hdl.handle.net/10356/151045 10.1126/sciadv.abe4323 33962958 2-s2.0-85105631394 19 7 eabe4323 en 1530700142 Science Advances © 2021 The Authors, some rights reserved; exclusive licensee American Association for the Advancement of Science. No claim to original U.S. Government Works. Distributed under a Creative Commons Attribution License 4.0 (CC BY). application/pdf
institution Nanyang Technological University
building NTU Library
continent Asia
country Singapore
Singapore
content_provider NTU Library
collection DR-NTU
language English
topic Science::Medicine
Brain
Neurons
spellingShingle Science::Medicine
Brain
Neurons
Phua, Siew Cheng
Tan, Yu Lin
Kok, Alison Maun Yeng
Senol, Esra
Chiam, Christine Jin Hui
Lee, Chun-Yao
Peng, Yanmin
Lim, Auriel Theodora Jacobea
Mohammad, Hasan
Lim, Jing-Xuan
Fu, Yu
A distinct parabrachial-to-lateral hypothalamus circuit for motivational suppression of feeding by nociception
description The motivation to eat is not only shaped by nutrition but also competed by external stimuli including pain. How the mouse hypothalamus, the feeding regulation center, integrates nociceptive inputs to modulate feeding is unclear. Within the key nociception relay center parabrachial nucleus (PBN), we demonstrated that neurons projecting to the lateral hypothalamus (LHPBN) are nociceptive yet distinct from danger-encoding central amygdala–projecting (CeAPBN) neurons. Activation of LHPBN strongly suppressed feeding by limiting eating frequency and also reduced motivation to work for food reward. Refined approach-avoidance paradigm revealed that suppression of LHPBN, but not CeAPBN, sustained motivation to obtain food. The effect of LHPBN neurons on feeding was reversed by suppressing downstream LHVGluT2 neurons. Thus, distinct from a circuit for fear and escape responses, LHPBN neurons channel nociceptive signals to LHVGluT2 neurons to suppress motivational drive for feeding. Our study provides a new perspective in understanding feeding regulation by external competing stimuli.
author2 Lee Kong Chian School of Medicine (LKCMedicine)
author_facet Lee Kong Chian School of Medicine (LKCMedicine)
Phua, Siew Cheng
Tan, Yu Lin
Kok, Alison Maun Yeng
Senol, Esra
Chiam, Christine Jin Hui
Lee, Chun-Yao
Peng, Yanmin
Lim, Auriel Theodora Jacobea
Mohammad, Hasan
Lim, Jing-Xuan
Fu, Yu
format Article
author Phua, Siew Cheng
Tan, Yu Lin
Kok, Alison Maun Yeng
Senol, Esra
Chiam, Christine Jin Hui
Lee, Chun-Yao
Peng, Yanmin
Lim, Auriel Theodora Jacobea
Mohammad, Hasan
Lim, Jing-Xuan
Fu, Yu
author_sort Phua, Siew Cheng
title A distinct parabrachial-to-lateral hypothalamus circuit for motivational suppression of feeding by nociception
title_short A distinct parabrachial-to-lateral hypothalamus circuit for motivational suppression of feeding by nociception
title_full A distinct parabrachial-to-lateral hypothalamus circuit for motivational suppression of feeding by nociception
title_fullStr A distinct parabrachial-to-lateral hypothalamus circuit for motivational suppression of feeding by nociception
title_full_unstemmed A distinct parabrachial-to-lateral hypothalamus circuit for motivational suppression of feeding by nociception
title_sort distinct parabrachial-to-lateral hypothalamus circuit for motivational suppression of feeding by nociception
publishDate 2021
url https://hdl.handle.net/10356/151045
_version_ 1759854006951215104