Murakami Dean M, Erkman Linda, Hermanson Ola, Rosenfeld Michael G, Fuller Charles A
Section of Neurobiology, Physiology, and Behavior, University of California, Davis, CA 95619-8519, USA.
Proc Natl Acad Sci U S A. 2002 Dec 24;99(26):17078-82. doi: 10.1073/pnas.252652299. Epub 2002 Dec 4.
Physiological responses to changes in the gravitational field and body position, as well as symptoms of patients with anxiety-related disorders, have indicated an interrelationship between vestibular function and stress responses. However, the relative significance of cochlear and vestibular information in autonomic regulation remains unresolved because of the difficulties in distinguishing the relative contributions of other proprioceptive and interoceptive inputs, including vagal and somatic information. To investigate the role of cochlear and vestibular function in central and physiological responses, we have examined the effects of increased gravity in wild-type mice and mice lacking the POU homeodomain transcription factor Brn-3.1 (Brn-3bPou4f3). The only known phenotype of the Brn-3.1(-/-) mouse is related to hearing and balance functions, owing to the failure of cochlear and vestibular hair cells to differentiate properly. Here, we show that normal physiological responses to increased gravity (2G exposure), such as a dramatic drop in body temperature and concomitant circadian adjustment, were completely absent in Brn-3.1(-/-) mice. In line with the lack of autonomic responses, the massive increase in neuronal activity after 2G exposure normally detected in wild-type mice was virtually abolished in Brn-3.1(-/-) mice. Our results suggest that cochlear and vestibular hair cells are the primary regulators of autonomic responses to altered gravity and provide genetic evidence that these cells are sufficient to alter neural activity in regions involved in autonomic and neuroendocrine control.
对重力场和身体位置变化的生理反应，以及焦虑相关障碍患者的症状，都表明前庭功能与应激反应之间存在相互关系。然而，由于难以区分包括迷走神经和躯体信息在内的其他本体感受和内感受输入的相对贡献，耳蜗和前庭信息在自主调节中的相对重要性仍未得到解决。为了研究耳蜗和前庭功能在中枢和生理反应中的作用，我们检测了野生型小鼠和缺乏POU同源结构域转录因子Brn-3.1（Brn-3bPou4f3）的小鼠在重力增加时的影响。Brn-3.1(-/-)小鼠唯一已知的表型与听力和平衡功能有关，这是由于耳蜗和前庭毛细胞未能正常分化所致。在这里，我们表明，Brn-3.1(-/-)小鼠完全没有对重力增加（暴露于2G）的正常生理反应，如体温急剧下降和随之而来的昼夜节律调整。与自主反应的缺乏一致，在野生型小鼠中通常检测到的2G暴露后神经元活动的大量增加在Brn-3.1(-/-)小鼠中几乎被消除。我们的结果表明，耳蜗和前庭毛细胞是对重力改变的自主反应的主要调节因子，并提供了遗传证据，证明这些细胞足以改变参与自主和神经内分泌控制的区域的神经活动。
