Dept. of Biological Sciences, Graduate School of Science, The University of Tokyo, 7-3-1 Hongo, Tokyo 113-0033, Japan.
J Neurophysiol. 2010 Mar;103(3):1375-84. doi: 10.1152/jn.00910.2009. Epub 2010 Jan 13.
The terminal nerve (TN)-gonadotropin-releasing hormone (GnRH) neurons have been suggested to function as a neuromodulatory system that regulates the motivational and arousal state of the animal and have served as a model system for the study of GnRH neuron physiology. To investigate the synaptic control of the TN-GnRH neurons, we analyzed electrophysiologically the effect of GABA on the TN-GnRH neurons. GABA generally hyperpolarizes most of the neurons in the adult brain by activating GABA(A) receptors while the activation of GABA(A) receptors depolarizes some specific neurons in the mature brain. Here we examined the GABA(A) receptor-mediated responses in the TN-GnRH neurons of adult teleost fish, the dwarf gourami, by means of gramicidin-perforated patch-clamp and cell-attached patch-clamp recordings. The reversal potential for the currents through GABA(A) receptors under the voltage clamp was depolarized relative to the resting membrane potential. GABA(A) receptor activation depolarized TN-GnRH neurons under the current clamp and had excitatory effect on their electrical activity, whereas the stronger GABA(A) receptor activation had bidirectional effect (excitatory-inhibitory). This excitatory effect is suggested to arise from high Cl(-) and was shown to be suppressed by bumetanide, the blocker of Cl(-)-accumulating sodium-potassium-2-chloride co-transporter (NKCC). The present results demonstrate that GABA(A) receptor activation induces excitation in TN-GnRH neurons, which may facilitate their neuromodulatory functions by increasing their spontaneous firing frequencies. The excitatory actions of GABA in the adult brain have recently been attracting much attention, and the easily accessible large TN-GnRH neurons should be a nice model system to analyze their physiological functions.
终端神经（TN）-促性腺激素释放激素（GnRH）神经元被认为是一种神经调节系统，调节动物的动机和唤醒状态，并作为 GnRH 神经元生理学研究的模型系统。为了研究 TN-GnRH 神经元的突触控制，我们分析了 GABA 对 TN-GnRH 神经元的电生理影响。GABA 通过激活 GABA(A)受体通常使成年大脑中的大多数神经元超极化，而在成熟大脑中，GABA(A)受体的激活使一些特定神经元去极化。在这里，我们通过革兰氏菌素穿孔膜片钳和细胞贴附膜片钳记录，研究了成年硬骨鱼， dwarf gourami 中的 TN-GnRH 神经元的 GABA(A)受体介导的反应。在电压钳下，通过 GABA(A)受体的电流的反转电位相对于静息膜电位去极化。GABA(A)受体的激活在电流钳下使 TN-GnRH 神经元去极化，并对其电活动产生兴奋作用，而更强的 GABA(A)受体激活具有双向作用（兴奋-抑制）。这种兴奋作用被认为是由高 Cl(-)引起的，并被 bumetanide（Cl(-)-积累钠钾-2-氯共转运体（NKCC）的阻断剂）抑制。本研究结果表明，GABA(A)受体的激活在 TN-GnRH 神经元中诱导兴奋，这可能通过增加其自发放电频率来促进其神经调节功能。最近，成年大脑中 GABA 的兴奋作用引起了广泛关注，而易于获得的大型 TN-GnRH 神经元应该是分析其生理功能的良好模型系统。
