Schreihofer Ann M, Guyenet Patrice G
Department of Pharmacology, University of Virginia Health System, Charlotttesville, Virginia 22908-0735, USA.
J Neurophysiol. 2003 Mar;89(3):1265-77. doi: 10.1152/jn.00737.2002. Epub 2002 Nov 20.
GABAergic neurons in the caudal ventrolateral medulla (CVLM) are believed to mediate the sympathetic baroreceptor reflex by inhibiting presympathetic neurons in the rostral ventrolateral medulla (RVLM). Accordingly, some CVLM neurons are activated by increased arterial pressure (AP; baro-activated), have activity strongly modulated by the AP pulse (pulse-modulated), and can be antidromically activated from the RVLM. This study examined whether baro-activated, pulse-modulated CVLM neurons are indeed GABAergic and examined their structures. We recorded extracellularly from 19 baro-activated, pulse-modulated CVLM neurons in chloralose-anesthetized rats. Most of these cells (13/19) were silenced by decreasing AP with nitroprusside, but some (6/19) remained active at low AP levels. They were also excited by phenyl biguanide (17/17) but inhibited by noxious tail pinch (8/11). Twelve baro-activated cells were filled with biotinamide and examined for expression of GAD67 mRNA. Because adjacent vagal motor neurons are also activated by increased AP, we examined choline acetyltransferase (ChAT) immunoreactivity. Most baro-activated cells (9/12) expressed high levels of GAD67 mRNA, the rest (3/12) displayed lower levels of GAD67 mRNA, but none showed ChAT immunoreactivity. In contrast, adjacent baro-inhibited CVLM cells had no GAD67 mRNA (n = 5) but were instead tyrosine hydroxylase immunoreactive (n = 7). Reconstruction of baro-activated CVLM neurons revealed axons that projected dorsomedially and rostrally with several axon collaterals. These data demonstrate the existence of GABAergic CVLM neurons with the physiological characteristics expected of interneurons that mediate the sympathetic baroreceptor reflex. In addition, baro-activated GABAergic CVLM neurons appear to integrate several types of inputs and provide inhibition to multiple targets.
延髓尾端腹外侧区（CVLM）的γ-氨基丁酸能神经元被认为通过抑制延髓头端腹外侧区（RVLM）的交感神经节前神经元来介导交感压力感受器反射。因此，一些CVLM神经元会因动脉血压（AP）升高而被激活（压力激活型），其活动受到AP脉冲的强烈调节（脉冲调制型），并且可以从RVLM进行逆向激活。本研究检测了压力激活型、脉冲调制型CVLM神经元是否确实为γ-氨基丁酸能神经元，并研究了它们的结构。我们在水合氯醛麻醉的大鼠中，对19个压力激活型、脉冲调制型CVLM神经元进行了细胞外记录。这些细胞中的大多数（13/19）会因硝普钠降低AP而沉默，但有些（6/19）在低AP水平时仍保持活跃。它们也会被苯乙双胍兴奋（17/17），但会被有害的尾部夹捏抑制（8/11）。12个压力激活型细胞用生物素酰胺填充，并检测GAD67 mRNA的表达。由于相邻的迷走运动神经元也会因AP升高而被激活，我们检测了胆碱乙酰转移酶（ChAT）免疫反应性。大多数压力激活型细胞（9/12）表达高水平的GAD67 mRNA，其余（3/12）显示较低水平的GAD67 mRNA，但均未显示ChAT免疫反应性。相比之下，相邻的压力抑制型CVLM细胞没有GAD67 mRNA（n = 5），但具有酪氨酸羟化酶免疫反应性（n = 7）。对压力激活型CVLM神经元的重建显示，轴突向背内侧和头端投射，并带有几个轴突侧支。这些数据证明了存在具有介导交感压力感受器反射的中间神经元预期生理特征的γ-氨基丁酸能CVLM神经元。此外，压力激活型γ-氨基丁酸能CVLM神经元似乎整合了多种类型的输入，并对多个靶点提供抑制作用。
