Compensatory changes in cellular excitability, not synaptic scaling, contribute to homeostatic recovery of embryonic network activity.
Compensatory changes in cellular excitability, not synaptic scaling, contribute to homeostatic recovery of embryonic network activity.
复制标题
细胞兴奋性的代偿性变化，而不是突触缩放，有助于胚胎网络活动的稳态恢复。
DOI：
10.1073/pnas.0813058106
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发表时间：
2009
影响因子：
11.1
通讯作者：
Wenner,Peter
中科院分区：
文献类型：
--
作者：
Wilhelm,JenniferC;Rich,MarkM;Wenner,Peter
当神经元活动在一段时间内减少时，突触强度和/或细胞兴奋性的代偿性变化被触发，这被认为是以稳态恢复正常活动水平的方式起作用。稳态突触强度和细胞兴奋性发生变化的时间过程尚不清楚。虽然许多研究表明，1-2天的活动阻滞是必要的，以触发兴奋性量子强度的增加，很少有研究能够检查这些机制是否实际上是网络活动恢复的基础。在这里，我们研究了在体内阻断兴奋性GABA能或谷氨酸能输入后胚胎运动活动恢复的机制。我们发现，GABA受体阻滞剂触发细胞兴奋性的快速变化，发生在活动的恢复，但在突触缩放的变化之前。这种细胞兴奋性的增加部分由钠电流的增加和快速失活和钙激活钾电流的减少介导。这些发现表明，细胞兴奋性的代偿性变化，而不是突触缩放，有助于活动恢复。此外，我们发现一个特殊的作用，GABAA受体在触发活动扰动后的几个稳态机制，包括细胞兴奋性和GABA能和AMP能突触强度的变化。细胞兴奋性和突触强度的稳态变化表达的时间差异表明，有多种机制和途径参与调节网络活动，并且每种机制和途径可能具有时间上不同的功能。
When neuronal activity is reduced over a period of days, compensatory changes in synaptic strength and/or cellular excitability are triggered, which are thought to act in a manner to homeostatically recover normal activity levels. The time course over which changes in homeostatic synaptic strength and cellular excitability occur are not clear. Although many studies show that 1–2 days of activity block are necessary to trigger increases in excitatory quantal strength, few studies have been able to examine whether these mechanisms actually underlie recovery of network activity. Here, we examine the mechanisms underlying recovery of embryonic motor activity following block of either excitatory GABAergic or glutamatergic inputs in vivo. We find that GABAAreceptor blockade triggers fast changes in cellular excitability that occur during the recovery of activity but before changes in synaptic scaling. This increase in cellular excitability is mediated in part by an increase in sodium currents and a reduction in the fast-inactivating and calcium-activated potassium currents. These findings suggest that compensatory changes in cellular excitability, rather than synaptic scaling, contribute to activity recovery. Further, we find a special role for the GABAAreceptor in triggering several homeostatic mechanisms after activity perturbations, including changes in cellular excitability and GABAergic and AMPAergic synaptic strength. The temporal difference in expression of homeostatic changes in cellular excitability and synaptic strength suggests that there are multiple mechanisms and pathways engaged to regulate network activity, and that each may have temporally distinct functions.