大脑功能的正常行使建立在其神经环路电活动稳态的基础上。当环路电活动受到扰动时（例如发生癫痫时高兴奋性），神经环路其它组件, 包括突触信息传递、神经元兴奋性和形态结构等也相应地发生改变，从而重建新稳态或恢复正常活动水平。这种环路活动自我调节机制称之为稳态调节，其发生的细胞机制是脑功能可塑性研究中一个重要课题。
10月21日的《神经科学杂志》（Journal of Neuroscience）发表了中国科学院上海生命科学研究院神经科学研究所关于稳态调节的新细胞机制发现——兴奋性突触活动通过内源大麻受体调节抑制性突触传递。在章晓辉研究员和蒲慕明研究员两个研究组的合作下，博士研究生张思宇、徐敏、缪庆龙通过脑片电生理记录，发现皮层内微小兴奋性突触活动的数小时缺失可以显著地减弱抑制性突触的功能，从而相应地减弱皮层环路中的抑制性。这个对抑制性突触的稳态调节依赖于内源大麻（Endocannabinoid）信号通路，以及由真核延伸因子-2（Eukaryotic Elongation Factor-2，eEF2）介导的蛋白合成。该研究的意义在于揭示了一种新的异突触机制调节皮层环路中兴奋性和抑制性之间的平衡（稳态），且发现了内源大麻（Endocannabinoid）信号参与稳态调节的新功能。这个研究发现可能为今后药物干预神经活动异常提供新的思路和途径。
该研究受到科技部“脑结构和功能的可塑性”973项目的资助。（生物谷Bioon.com）
生物谷推荐原始出处：
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.
