Kuzmiski J Brent, Pittman Quentin J, Bains Jaideep S
Hotchkiss Brain Institute, University of Calgary, Calgary, AB T2N4N1, Canada.
Neuron. 2009 Jun 25;62(6):839-49. doi: 10.1016/j.neuron.2009.05.027.
Neural networks that regulate an organism's internal environment must sense perturbations, respond appropriately, and then reset. These adaptations should be reflected as changes in the efficacy of the synapses that drive the final output of these homeostatic networks. Here we show that hemorrhage, an in vivo challenge to fluid homeostasis, induces LTD at glutamate synapses onto hypothalamic magnocellular neurosecretory cells (MNCs). LTD requires the activation of postsynaptic alpha2-adrenoceptors and the production of endocannabinoids that act in a retrograde fashion to inhibit glutamate release. In addition, both hemorrhage and noradrenaline downregulate presynaptic group III mGluRs. This loss of mGluR function allows high-frequency activity to potentiate these synapses from their depressed state. These findings demonstrate that noradrenaline controls a form of metaplasticity that may underlie the resetting of homeostatic networks following a successful response to an acute physiological challenge.
调节生物体内部环境的神经网络必须感知扰动、做出适当反应，然后进行重置。这些适应性变化应表现为驱动这些稳态网络最终输出的突触效能的改变。在这里，我们表明出血作为对液体稳态的一种体内挑战，可诱导下丘脑大细胞神经分泌细胞（MNCs）上谷氨酸突触的长时程抑制（LTD）。LTD需要激活突触后α2-肾上腺素能受体并产生以内向逆行方式作用以抑制谷氨酸释放的内源性大麻素。此外，出血和去甲肾上腺素均可下调突触前III组代谢型谷氨酸受体（mGluRs）。mGluR功能的这种丧失使高频活动能够将这些突触从其抑制状态增强。这些发现表明去甲肾上腺素控制着一种可塑性变化形式，这可能是在对急性生理挑战做出成功反应后稳态网络重置的基础。
