Dergacheva Olga, Yamanaka Akihiro, Schwartz Alan R, Polotsky Vsevolod Y, Mendelowitz David
Department of Pharmacology and Physiology, The George Washington University, 2300 Eye Street, NW, Washington, DC 20037, USA.
Research Institute of Environmental Medicine, Nagoya University, Nagoya 464-8601, Japan.
Neuroscience. 2016 Dec 17;339:47-53. doi: 10.1016/j.neuroscience.2016.09.038. Epub 2016 Sep 28.
Orexin neurons are known to augment the sympathetic control of cardiovascular function, however the role of orexin neurons in parasympathetic cardiac regulation remains unclear. To test the hypothesis that orexin neurons contribute to parasympathetic control we selectively expressed channelrhodopsin-2 (ChR2) in orexin neurons in orexin-Cre transgenic rats and examined postsynaptic currents in cardiac vagal neurons (CVNs) in the dorsal motor nucleus of the vagus (DMV). Simultaneous photostimulation and recording in ChR2-expressing orexin neurons in the lateral hypothalamus resulted in reliable action potential firing as well as large whole-cell currents suggesting a strong expression of ChR2 and reliable optogenetic excitation. Photostimulation of ChR2-expressing fibers in the DMV elicited short-latency (ranging from 3.2ms to 8.5ms) postsynaptic currents in 16 out of 44 CVNs tested. These responses were heterogeneous and included excitatory glutamatergic (63%) and inhibitory GABAergic (37%) postsynaptic currents. The results from this study suggest different sub-population of orexin neurons may exert diverse influences on brainstem CVNs and therefore may play distinct functional roles in parasympathetic control of the heart.
已知食欲素神经元可增强对心血管功能的交感神经控制，然而食欲素神经元在副交感神经心脏调节中的作用仍不清楚。为了验证食欲素神经元参与副交感神经控制这一假设，我们在食欲素-Cre转基因大鼠的食欲素神经元中选择性表达了通道视紫红质-2（ChR2），并检测了迷走神经背核（DMV）中心脏迷走神经元（CVN）的突触后电流。在下丘脑外侧对表达ChR2的食欲素神经元进行同步光刺激和记录，结果显示可产生可靠的动作电位发放以及大的全细胞电流，这表明ChR2表达强烈且光遗传学激发可靠。对DMV中表达ChR2的纤维进行光刺激，在44个受试CVN中的16个中诱发了短潜伏期（3.2毫秒至8.5毫秒）的突触后电流。这些反应具有异质性，包括兴奋性谷氨酸能突触后电流（63%）和抑制性γ-氨基丁酸能突触后电流（37%）。本研究结果表明，不同亚群的食欲素神经元可能对脑干CVN产生不同影响，因此可能在心脏的副交感神经控制中发挥不同的功能作用。
