Medullary pathways mediating specific sympathetic responses to activation of dorsomedial hypothalamus
Medullary pathways mediating specific sympathetic responses to activation of dorsomedial hypothalamus
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DOI：
10.1016/j.neuroscience.2004.03.013
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发表时间：
2004-01-01
期刊：
影响因子：
3.3
通讯作者：
Morrison, SF
中科院分区：
文献类型：
--
作者：
Cao, WH;Fan, W;Morrison, SF
我们试图确定哪些髓质交感前运动神经元介导由尿烷/氯醛糖麻醉、人工通气大鼠的下丘脑背内侧 (DMH) 神经元激活引起的心血管和产热效应。通过显微注射荷包牡丹碱（2 mM，30 nl）对 DMH 中的神经元进行单侧去抑制，导致棕色脂肪组织交感神经活动显着增加（BAT SNA，+828+/-169% 对照，n=16）、心脏 SNA（+516+/-82% 对照，n=16）、肾 SNA（RSNA，+203+/-25% 对照，n=28）并且，伴随着 BAT 温度（+1.6+/-0.3 摄氏度，n=11）、呼气末二氧化碳（+0.7+/-0.1%，n=15）、心率（+113+/-7 次/分钟，n=32）、动脉压（+19+/-2 mm Hg，n=32）以及血浆肾上腺素和去甲肾上腺素浓度的增加。通过显微注射蝇蕈醇（6 mM，60 nl）抑制中缝苍白核（RPa）神经元，消除了 BAT SNA 和 BAT 温度的增加，并减少了 DMH 神经元去抑制引起的心动过速。通过显微注射蝇蕈醇（6 mM，60 nl）抑制 RVLM 中的神经元，显着减少 RSNA 的增加，但不影响诱发的心动过速或动脉压的增加。结合谷氨酸脱羧酶 (GAD-67) 免疫细胞化学和来自 BAT 的伪狂犬病病毒逆行追踪表明 BAT 交感神经通路中 GABA 能末端和 DMH 神经元之间的紧密结合。总之，这些结果表明，DMH 中神经元存在紧张活性、GABA 能抑制输入，并且阻断这种抑制会通过激活功能上特定的交感前运动神经元群体，增加交感神经向生热和心血管靶标的流出：BAT SNA 和 BAT 生热作用的兴奋是通过 RPa 中推定的交感前运动神经元介导的，而 RSNA 的激活则依赖于 RVLM 中的交感前运动神经元。这些数据增加了我们对调节交感神经介导的生热作用变化的中心途径的理解，该生热作用在温度调节、应激反应和能量平衡中被激活。 (C) 2004 年国际广播组织。由爱思唯尔有限公司出版。保留所有权利。
We sought to determine which medullary sympathetic premotor neurons mediate the cardiovascular and thermogenic effects resulting from activation of neurons in the dorsomedial hypothalamus (DMH) in urethane/chloralose-anesthetized, artificially ventilated rats. Unilateral disinhibition of neurons in the DMH with microinjection of bicuculline (2 mM, 30 nl) caused significant increases in brown adipose tissue sympathetic nerve activity (BAT SNA, +828+/-169% of control, n=16), cardiac SNA (+516+/-82% of control, n=16), renal SNA (RSNA, +203+/-25% of control, n=28) and, accompanied by increases in BAT temperature (+1.6+/-0.3 degreesC, n=11), end-tidal CO2 (+0.7+/-0.1%, n=15), heart rate (+113+/-7 beats/min, n=32), arterial pressure (+19+/-2 mm Hg, n=32) and plasma epinephrine and norepinephrine concentrations. Inhibition of neurons in the rostral raphe pallidus (RPa) with microinjection of muscimol (6 mM, 60 nl) abolished the increases in BAT SNA and BAT temperature and reduced the tachycardia induced by disinhibition of DMH neurons. Inhibition of neurons in the RVLM with microinjection of muscimol (6 mM, 60 nl) markedly reduced the increase in RSNA, but did not affect the evoked tachycardia or the increase in arterial pressure. Combined glutamic acid decarboxylase (GAD-67) immunocytochemistry and pseudorabies viral retrograde tracing from BAT indicated close appositions between GABAergic terminals and DMH neurons in sympathetic pathways to BAT. In conclusion, these results demonstrate the existence of a tonically active, GABAergic inhibitory input to neurons in the DMH and that blockade of this inhibition increases sympathetic outflow to thermogenic and cardiovascular targets by activating functionally specific populations of sympathetic premotor neurons: the excitation of BAT SNA and BAT thermogenesis is mediated through putative sympathetic premotor neurons in the RPa, while the activation in RSNA is dependent on those in RVLM. These data increase our understanding of the central pathways mediating changes in sympathetically mediated thermogenesis that is activated in thermoregulation, stress responses and energy balance. (C) 2004 IBRO. Published by Elsevier Ltd. All rights reserved.