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  • Perspective
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A hypothalamomedullary network for physiological responses to environmental stresses

Nature Reviews Neuroscience volume 23, pages 35–52 (2022)Cite this article

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Abstract

Various environmental stressors, such as extreme temperatures (hot and cold), pathogens, predators and insufficient food, can threaten life. Remarkable progress has recently been made in understanding the central circuit mechanisms of physiological responses to such stressors. A hypothalamomedullary neural pathway from the dorsomedial hypothalamus (DMH) to the rostral medullary raphe region (rMR) regulates sympathetic outflows to effector organs for homeostasis. Thermal and infection stress inputs to the preoptic area dynamically alter the DMH → rMR transmission to elicit thermoregulatory, febrile and cardiovascular responses. Psychological stress signalling from a ventromedial prefrontal cortical area to the DMH drives sympathetic and behavioural responses for stress coping, representing a psychosomatic connection from the corticolimbic emotion circuit to the autonomic and somatic motor systems. Under starvation stress, medullary reticular neurons activated by hunger signalling from the hypothalamus suppress thermogenic drive from the rMR for energy saving and prime mastication to promote food intake. This Perspective presents a combined neural network for environmental stress responses, providing insights into the central circuit mechanism for the integrative regulation of systemic organs.

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Fig. 1: A schematic diagram of the central pathways for environmental stress signalling in rodents.
Fig. 2: A model of the network mechanism for physiological responses to environmental stresses.
Fig. 3: Preoptic area local circuit for thermal and infection stress responses.
Fig. 4: Indispensable roles of the DP/DTT → DMH pathway in physiological responses to psychological stress but not in basal homeostasis.
Fig. 5: A model of the hypothalamomedullary network mechanism for physiological responses to starvation stress.

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Acknowledgements

The authors have been supported by the Funding Program for Next Generation World-Leading Researchers from the Japan Society for the Promotion of Science (LS070 to K.N.); Grants-in-Aid for Scientific Research (20H03418, 16H05128, 15H05932, 26118508, 26713009 and 22689007 to K.N.; 21K06767, 17K08568, 26860159 and 23790271 to Y.N.; 19K06954 and 16K19006 to N.K.) from the Ministry of Education, Culture, Sports, Science and Technology of Japan; the PRESTO program (JPMJPR13M9 to K.N.) and Moonshot R&D (JPMJMS2023 to K.N.) of the Japan Science and Technology Agency; the Japan Agency for Medical Research and Development (JP21gm5010002 to K.N.; JP21wm0525002 to N.K.); and by grants from the Takeda Science Foundation, Nakajima Foundation, Uehara Memorial Foundation, Ono Medical Research Foundation, Brain Science Foundation, Kowa Life Science Foundation (to K.N.), Hori Sciences and Arts Foundation (to Y.N.), Kato Memorial Bioscience Foundation and Foundation of Kinoshita Memorial Enterprise (to N.K.).

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  1. Department of Integrative Physiology, Nagoya University Graduate School of Medicine, Nagoya, Japan

    Kazuhiro Nakamura, Yoshiko Nakamura & Naoya Kataoka

  2. Nagoya University Institute for Advanced Research, Nagoya, Japan

    Naoya Kataoka

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K.N. wrote the article. All the authors researched data for the article and made substantial contributions to discussions of its content and reviewed and edited the manuscript before submission.

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Nakamura, K., Nakamura, Y. & Kataoka, N. A hypothalamomedullary network for physiological responses to environmental stresses. Nat Rev Neurosci 23, 35–52 (2022). https://doi.org/10.1038/s41583-021-00532-x

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