Reduction in endocannabinoid tone is a homeostatic mechanism for specific inhibitory synapses.
Reduction in endocannabinoid tone is a homeostatic mechanism for specific inhibitory synapses.
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DOI：
10.1038/nn.2517
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发表时间：
2010-05
影响因子：
25
通讯作者：
Alger, Bradley E.
中科院分区：
文献类型：
--
作者：
Kim, Jimok;Alger, Bradley E.
当神经元活动发生慢性改变时，网络增益由突触强度的全局稳态缩放来维持，但微电路的稳定性可以通过不同于全局变化的独特适应来控制。突触调谐的特异性是如何实现的还不清楚。在这里，我们报告说，虽然大量的抑制性突触在长期不活动后被稳态缩小，但内源性大麻素张力的降低特异性地增强了表达大麻素受体的GABA能突触的一个子集。在大鼠的海马切片培养物中，神经元放电的3-5天阻断促进花生四烯酸的摄取和降解。大麻素受体的基础刺激随之减少，增加了GABA释放的可能性，从而促进了突触抑制和按需去抑制的快速抑制。这种新的调节机制，介导的活性依赖性的变化，紧张性内源性大麻素水平，允许选择性的局部调整抑制性突触在海马网络。
When chronic alterations in neuronal activity occur, network gain is maintained by global homeostatic scaling of synaptic strength, but the stability of microcircuits can be controlled by unique adaptations that differ from the global changes. It is not understood how specificity of synaptic tuning is achieved. Here we report that, while a large population of inhibitory synapses is homeostatically scaled down after chronic inactivity, decreased endocannabinoid tone specifically strengthens a subset of GABAergic synapses that express cannabinoid receptors. In hippocampal slice cultures of rats, a 3–5 day blockade of neuronal firing facilitates uptake and degradation of anandamide. The consequent reduction in basal stimulation of cannabinoid receptors augments GABA release probability, thus fostering rapid depression of synaptic inhibition and on-demand disinhibition. This novel regulatory mechanism, mediated by activity-dependent changes in tonic endocannabinoid level, permits selective local tuning of inhibitory synapses in hippocampal networks.
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