Department of Pharmacology, University of Virginia, Charlottesville, VA 22908, USA.
J Neurosci. 2013 Feb 13;33(7):3164-77. doi: 10.1523/JNEUROSCI.1046-12.2013.
Activation of rostral ventrolateral medullary catecholaminergic (RVLM-CA) neurons e.g., by hypoxia is thought to increase sympathetic outflow thereby raising blood pressure (BP). Here we test whether these neurons also regulate breathing and cardiovascular variables other than BP. Selective expression of ChR2-mCherry by RVLM-CA neurons was achieved by injecting Cre-dependent vector AAV2-EF1α-DIO-ChR2-mCherry unilaterally into the brainstem of dopamine-β-hydroxylase(Cre/0) mice. Photostimulation of RVLM-CA neurons increased breathing in anesthetized and conscious mice. In conscious mice, photostimulation primarily increased breathing frequency and this effect was fully occluded by hypoxia (10% O(2)). In contrast, the effects of photostimulation were largely unaffected by hypercapnia (3 and 6% CO(2)). The associated cardiovascular effects were complex (slight bradycardia and hypotension) and, using selective autonomic blockers, could be explained by coactivation of the sympathetic and cardiovagal outflows. ChR2-positive RVLM-CA neurons expressed VGLUT2 and their projections were mapped. Their complex cardiorespiratory effects are presumably mediated by their extensive projections to supraspinal sites such as the ventrolateral medulla, the dorsal vagal complex, the dorsolateral pons, and selected hypothalamic nuclei (dorsomedial, lateral, and paraventricular nuclei). In sum, selective optogenetic activation of RVLM-CA neurons in conscious mice revealed two important novel functions of these neurons, namely breathing stimulation and cardiovagal outflow control, effects that are attenuated or absent under anesthesia and are presumably mediated by the numerous supraspinal projections of these neurons. The results also suggest that RVLM-CA neurons may underlie some of the acute respiratory response elicited by carotid body stimulation but contribute little to the central respiratory chemoreflex.
延髓头端腹外侧区儿茶酚胺能神经元（RVLM-CA）的激活，例如由缺氧引起的激活，被认为会增加交感神经输出，从而升高血压（BP）。在这里，我们测试这些神经元是否还调节除血压以外的呼吸和心血管变量。通过将 Cre 依赖性载体 AAV2-EF1α-DIO-ChR2-mCherry 单侧注射到多巴胺-β-羟化酶（Cre/0）小鼠的脑干中，实现了 RVLM-CA 神经元中 ChR2-mCherry 的选择性表达。RVLM-CA 神经元的光刺激增加了麻醉和清醒小鼠的呼吸。在清醒小鼠中，光刺激主要增加呼吸频率，而这种效应被缺氧（10% O(2)）完全阻断。相比之下，光刺激的效应受高碳酸血症（3%和 6% CO(2)）的影响不大。相关的心血管效应较为复杂（轻微的心动过缓和低血压），并且使用选择性自主神经阻滞剂，可以通过交感神经和迷走神经输出的共同激活来解释。ChR2 阳性 RVLM-CA 神经元表达 VGLUT2，并且它们的投射被映射。它们复杂的心肺效应可能是通过其广泛投射到延髓腹外侧区、迷走神经复合体、脑桥背外侧、以及选定的下丘脑核（背内侧、外侧和旁室核）等上位脑区来介导的。总之，在清醒小鼠中选择性光遗传学激活 RVLM-CA 神经元揭示了这些神经元的两个重要新功能，即呼吸刺激和迷走神经输出控制，这些效应在麻醉下减弱或不存在，并且可能是由这些神经元的众多上位投射介导的。结果还表明，RVLM-CA 神经元可能是颈动脉体刺激引起的一些急性呼吸反应的基础，但对中枢呼吸化学反射的贡献很小。
