Spontaneous Release Regulates Synaptic Scaling in the Embryonic Spinal Network In Vivo
Spontaneous Release Regulates Synaptic Scaling in the Embryonic Spinal Network In Vivo
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DOI：
10.1523/jneurosci.4066-15.2016
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发表时间：
2016-07-06
影响因子：
5.3
通讯作者：
Wenner, Peter
中科院分区：
文献类型：
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作者：
Angel Garcia-Bereguiain, Miguel;Gonzalez-Islas, Carlos;Wenner, Peter
稳态可塑性机制通过突触强度或内在细胞兴奋性的代偿性变化维持细胞或网络尖峰活动在生理功能范围内。突触缩放（Synaptic scaling）是一种自稳态可塑性，它是在阻断峰值或神经传递后触发的，在这种情况下，细胞所有突触输入的强度以代偿方式成倍地向上或向下缩放。我们之前已经证明，在体内完全阻断峰值或GABA(A)受体（GABA(A)R）激活2天后，可以触发小鸡胚胎脊髓运动神经元突触升级。在这里，我们通过使用尼古丁调节剂或mGluR2激动剂慢性调节体内突触前GABA释放，以更生理相关的方式改变GABA(A)R的激活。以这种方式操纵GABA(A)R的激活触发了与完全阻断GABA(A)R诱导的尺度相似的机制。值得注意的是，我们发现改变动作电位（AP）独立的自发释放能够完全解释观察到的双向标度，而与自发网络活动相关的峰值活动的剧烈变化对量子振幅的影响很小。对ap独立过程的依赖挑战了可塑性与活胚胎脊髓网络中尖峰的关系。我们的研究结果对突触缩放的触发和功能有一定的影响，并表明自发释放功能在体内动态调节突触强度。
Homeostatic plasticity mechanisms maintain cellular or network spiking activity within a physiologically functional range through compensatory changes in synaptic strength or intrinsic cellular excitability. Synaptic scaling is one form of homeostatic plasticity that is triggered after blockade of spiking or neurotransmission in which the strengths of all synaptic inputs to a cell are multiplicatively scaled upward or downward in a compensatory fashion. We have shown previously that synaptic upscaling could be triggered in chick embryo spinal motoneurons by complete blockade of spiking or GABA(A) receptor (GABA(A)R) activation for 2 d in vivo. Here, we alter GABA(A)R activation in a more physiologically relevant manner by chronically adjusting presynaptic GABA release in vivo using nicotinic modulators or an mGluR2 agonist. Manipulating GABA(A)R activation in this way triggered scaling in a mechanistically similar manner to scaling induced by complete blockade of GABA(A)Rs. Remarkably, we find that altering action-potential (AP)-independent spontaneous release was able to fully account for the observed bidirectional scaling, whereas dramatic changes in spiking activity associated with spontaneous network activity had little effect on quantal amplitude. The reliance of scaling on an AP-independent process challenges the plasticity's relatedness to spiking in the living embryonic spinal network. Our findings have implications for the trigger and function of synaptic scaling and suggest that spontaneous release functions to regulate synaptic strength homeostatically in vivo.