Hewitt Sarah A, Wamsteeker Jaclyn I, Kurz Ebba U, Bains Jaideep S
Hotchkiss Brain Institute, University of Calgary, Calgary, Alberta, Canada.
Nat Neurosci. 2009 Apr;12(4):438-43. doi: 10.1038/nn.2274. Epub 2009 Mar 1.
In mammals, stress elicits a stereotyped endocrine response that requires an increase in the activity of hypothalamic parvocellular neuroendocrine neurons. The output of these cells is normally constrained by powerful GABA-mediated synaptic inhibition. We found that acute restraint stress in rats released the system from inhibitory synaptic drive in vivo by down-regulating the transmembrane anion transporter KCC2. This manifested as a depolarizing shift in the reversal potential of GABA(A)-mediated synaptic currents that rendered GABA inputs largely ineffective. Notably, repetitive activation of GABA synapses after stress resulted in a more rapid collapse of the anion gradient and was sufficient to increase the activity of neuroendocrine cells. Our data indicate that hypothalamic neurons integrate psychological cues to mount the endocrine response to stress by regulating anion gradients.
在哺乳动物中，应激会引发一种刻板的内分泌反应，这需要下丘脑小细胞神经内分泌神经元的活动增加。这些细胞的输出通常受到强大的GABA介导的突触抑制的限制。我们发现，大鼠的急性束缚应激通过下调跨膜阴离子转运体KCC2，在体内使该系统从抑制性突触驱动中释放出来。这表现为GABA(A)介导的突触电流反转电位的去极化转变，使GABA输入基本无效。值得注意的是，应激后GABA突触的重复激活导致阴离子梯度更快地崩溃，并且足以增加神经内分泌细胞的活动。我们的数据表明，下丘脑神经元通过调节阴离子梯度来整合心理线索，以启动对应激的内分泌反应。
