Department of Cellular and Integrative Physiology, College of Medicine, University of Texas Health Science Center at San Antonio, San Antonio, Texas.
Department of Physiology, College of Medicine, University of Kentucky, Lexington, Kentucky.
J Neurophysiol. 2019 Nov 1;122(5):2130-2141. doi: 10.1152/jn.00039.2019. Epub 2019 Oct 9.
The dorsal motor nucleus of the vagus (DMV) contains the preganglionic motor neurons important in the regulation of glucose homeostasis and gastrointestinal function. Despite the role of sex in the regulation of these processes, few studies examine the role of sex and/or ovarian cycle in the regulation of synaptic neurotransmission to the DMV. Since GABAergic neurotransmission is critical to normal DMV function, the present study used in vitro whole cell patch-clamping to investigate whether sex differences exist in GABAergic neurotransmission to DMV neurons. It additionally investigated whether the ovarian cycle plays a role in those sex differences. The frequency of phasic GABA receptor-mediated inhibitory postsynaptic currents in DMV neurons from females was lower compared with males, and this effect was TTX sensitive and abolished by ovariectomy (OVX). Amplitudes of GABAergic currents (both phasic and tonic) were not different. However, females demonstrated significantly more variability in the amplitude of both phasic and tonic GABA receptor currents. This difference was eliminated by OVX in females, suggesting that these differences were related to reproductive hormone levels. This was confirmed for GABAergic tonic currents by comparing females in two ovarian stages, estrus versus diestrus. Female mice in diestrus had larger tonic current amplitudes compared with those in estrus, and this increase was abolished after administration of a 5α-reductase inhibitor but not modulation of estrogen. Taken together, these findings demonstrate that DMV neurons undergo GABA receptor activity plasticity as a function of sex and/or sex steroids. Results show that GABAergic signaling in dorsal vagal motor neurons (DMV) demonstrates sex differences and fluctuates across the ovarian cycle in females. These findings are the first to demonstrate that female GABA receptor activity in this brain region is modulated by 5α-reductase-dependent hormones. Since DMV activity is critical to both glucose and gastrointestinal homeostasis, these results suggest that sex hormones, including those synthesized by 5α-reductase, contribute to visceral, autonomic function related to these physiological processes.
迷走神经背核（DMV）中的背运动核含有调节葡萄糖稳态和胃肠道功能的重要节前运动神经元。尽管性别在这些过程的调节中起作用，但很少有研究检查性别和/或卵巢周期在调节迷走神经背核的突触神经传递中的作用。由于 GABA 能神经传递对 DMV 正常功能至关重要，因此本研究使用体外全细胞膜片钳技术研究 DMV 神经元的 GABA 能神经传递是否存在性别差异。它还研究了卵巢周期是否在这些性别差异中起作用。与雄性相比，雌性 DMV 神经元中 GABA 受体介导的突触后抑制性电流的相频较低，这种效应对 TTX 敏感，并被卵巢切除术（OVX）消除。GABA 能电流（包括相频和紧张）的幅度没有差异。然而，雌性在相频和紧张性 GABA 受体电流的幅度上表现出明显更大的可变性。OVX 消除了雌性的这种差异，表明这些差异与生殖激素水平有关。通过比较发情期和发情间期的两个卵巢阶段的雌性来证实 GABA 能紧张性电流的这种差异。发情间期的雌性小鼠比发情期的雌性小鼠具有更大的紧张性电流幅度，并且这种增加在给予 5α-还原酶抑制剂后被消除，但雌激素的调节没有被消除。综上所述，这些发现表明 DMV 神经元作为性别和/或性激素的函数经历 GABA 受体活性可塑性。结果表明，背侧迷走运动神经元（DMV）中的 GABA 能信号传递存在性别差异，并在雌性中随卵巢周期而波动。这些发现是首次表明该脑区的雌性 GABA 受体活性受 5α-还原酶依赖性激素调节。由于 DMV 活性对葡萄糖和胃肠道稳态至关重要，这些结果表明，性激素，包括由 5α-还原酶合成的性激素，有助于与这些生理过程相关的内脏、自主功能。
