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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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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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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DOI: https://doi.org/10.1038/s41583-021-00532-x
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