Effects of disinhibition of neurons in the dorsomedial hypothalamus on central respiratory drive
Effects of disinhibition of neurons in the dorsomedial hypothalamus on central respiratory drive
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DOI：
10.1152/ajpregu.00503.2007
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发表时间：
2007-10-01
影响因子：
2.8
通讯作者：
Dampney, Roger A. L.
中科院分区：
文献类型：
--
作者：
McDowall, Lachlan M.;Horiuchi, Jouji;Dampney, Roger A. L.
下丘脑背内侧（DMH）内的神经元在心理应激下的心血管和神经内分泌反应中起关键作用。呼吸活动的增加也是对心理应激的生理反应的一个特征，但关于DMH神经元在调节呼吸活动中的作用的研究很少。在本研究中，我们测定了DMH神经元激活对自主呼吸的大鼠呼吸活动的影响（通过测量膈神经活动，PNA来评估），以及引起的呼吸活动变化与交感血管舒缩活动变化之间的关系。在DMH中微量注射双库兰（4-40 pmol / 20 nl）可引起PNA爆发频率和幅度的剂量依赖性增加。这些都伴随着平均气管二氧化碳水平的剂量依赖性下降，表明过度通气。在对照实验中，向DMH附近的位点微量注射双球茎碱引起的PNA变化要小得多，甚至没有变化。在测量肾交感神经活动（RSNA）的实验中，周期触发平均显示静息条件下的RSNA与PNA部分相关，但在DMH去抑制的反应中，RSNA呼吸相关变化的幅度没有一致的变化。结果表明，DMH神经元可以对呼吸活动产生强大的刺激作用，引起过度通气。这与PNA和RSNA之间耦合程度的增加无关，表明dmh诱发的RSNA增加不是中枢呼吸驱动增加的结果。
Neurons within the dorsomedial hypothalamus (DMH) play a critical role in subserving the cardiovascular and neuroendocrine response to psychological stress. An increase in respiratory activity is also a characteristic feature of the physiological response to psychological stress, but there have been few studies of the role of DMH neurons in regulating respiratory activity. In this study we determined the effects of activation of DMH neurons on respiratory activity (assessed by measuring phrenic nerve activity, PNA) and the relationship between evoked changes in respiratory activity and changes in sympathetic vasomotor activity in spontaneously breathing urethane-anesthetized rats. Microinjections of bicuculline (4-40 pmol in 20 nl) into the DMH evoked dose-dependent increases in PNA burst frequency and amplitude. These were accompanied by dose-dependent decreases in mean tracheal CO2 levels, indicative of hyperventilation. In control experiments, microinjections of bicuculline, into sites adjacent to the DMH evoked much smaller or no changes in PNA. In experiments where renal sympathetic nerve activity (RSNA) was also measured, cycle-triggered averaging revealed that RSNA under resting conditions was partly correlated with the PNA, but in response to DMH disinhibition there was no consistent change in the amplitude of the respiratory-related variations in RSNA. The results indicate that DMH neurons can exert a powerful stimulatory effect on respiratory activity, causing hyperventilation. This is not associated with an increase in the degree of coupling between PNA and RSNA, indicating that the DMH-evoked increase in RSNA is not a consequence of increased central respiratory drive.