大腦功能的正常行使建立在其神經(jīng)環(huán)路電活動穩(wěn)態(tài)的基礎上,。當環(huán)路電活動受到擾動時（例如發(fā)生癲癇時高興奮性）,，神經(jīng)環(huán)路其它組件, 包括突觸信息傳遞、神經(jīng)元興奮性和形態(tài)結(jié)構(gòu)等也相應地發(fā)生改變,，從而重建新穩(wěn)態(tài)或恢復正?；顒铀?。這種環(huán)路活動自我調(diào)節(jié)機制稱之為穩(wěn)態(tài)調(diào)節(jié),，其發(fā)生的細胞機制是腦功能可塑性研究中一個重要課題,。
10月21日的《神經(jīng)科學雜志》（Journal of Neuroscience）發(fā)表了中國科學院上海生命科學研究院神經(jīng)科學研究所關于穩(wěn)態(tài)調(diào)節(jié)的新細胞機制發(fā)現(xiàn)——興奮性突觸活動通過內(nèi)源大麻受體調(diào)節(jié)抑制性突觸傳遞。在章曉輝研究員和蒲慕明研究員兩個研究組的合作下,，博士研究生張思宇,、徐敏、繆慶龍通過腦片電生理記錄,，發(fā)現(xiàn)皮層內(nèi)微小興奮性突觸活動的數(shù)小時缺失可以顯著地減弱抑制性突觸的功能，從而相應地減弱皮層環(huán)路中的抑制性,。這個對抑制性突觸的穩(wěn)態(tài)調(diào)節(jié)依賴于內(nèi)源大麻（Endocannabinoid）信號通路,，以及由真核延伸因子-2（Eukaryotic Elongation Factor-2，eEF2）介導的蛋白合成,。該研究的意義在于揭示了一種新的異突觸機制調(diào)節(jié)皮層環(huán)路中興奮性和抑制性之間的平衡（穩(wěn)態(tài)）,，且發(fā)現(xiàn)了內(nèi)源大麻（Endocannabinoid）信號參與穩(wěn)態(tài)調(diào)節(jié)的新功能。這個研究發(fā)現(xiàn)可能為今后藥物干預神經(jīng)活動異常提供新的思路和途徑,。
該研究受到科技部“腦結(jié)構(gòu)和功能的可塑性”973項目的資助,。（生物谷Bioon.com）
生物谷推薦原始出處：
The Journal of Neuroscience, October 21, 2009, 29(42):13222-13231; doi:10.1523/JNEUROSCI.1710-09.2009
Endocannabinoid-Dependent Homeostatic Regulation of Inhibitory Synapses by Miniature Excitatory Synaptic Activities
Si-yu Zhang,1 * Min Xu,1 * Qing-long Miao,1 Mu-ming Poo,1,2 and Xiao-hui Zhang1
1Institute of Neuroscience and State Key Laboratory of Neuroscience, Shanghai Institutes for Biological Sciences, Chinese Academy of Sciences, Shanghai 200031, China, and 2Division of Neurobiology, Department of Molecular and Cell Biology, Helen Wills Neuroscience Institute, University of California, Berkeley, California 94720
Homeostatic regulation of synaptic strength in response to persistent changes of neuronal activity plays an important role in maintaining the overall level of circuit activity within a normal range. Absence of miniature EPSCs (mEPSCs) for a few hours is known to cause upregulation of excitatory synaptic strength, suggesting that mEPSCs contribute to the maintenance of excitatory synaptic functions. In the present study, we found that the absence of mEPSCs for 1–3 h also resulted in homeostatic suppression of presynaptic functions of inhibitory synapses in acute cortical slices from juvenile rats, as suggested by the reduced frequency (but not amplitude) of miniature IPSCs (mIPSCs) as well as the reduced amplitude of IPSCs. This homeostatic regulation depended on endocannabinoid (eCB) signaling, because blockade of either the activation of cannabinoid type-1 receptors (CB1Rs) or the synthesis of its endogenous ligand 2-arachidonoylglycerol (2-AG) abolished the suppression of inhibitory synapses caused by the absence of mEPSCs. Blockade of group I metabotropic glutamate receptors (mGluR-I) also abolished the suppression of inhibitory synapses, consistent with the mGluR-I requirement for eCB synthesis and release in cortical synapses. Furthermore, this homeostatic regulation also required eukaryotic elongation factor-2 (eEF2)-dependent protein synthesis, but not gene transcription. Activation of eEF2 alone was sufficient to suppress the mIPSC frequency, an effect abolished by inhibiting CB1Rs. Thus, mEPSCs contribute to the maintenance of inhibitory synaptic function and the absence of mEPSCs results in presynaptic suppression of inhibitory synapses via protein synthesis-dependent elevation of eCB signaling.
