于翔研究組發(fā)表了題為“Postsynaptic spiking homeostatically induces cell-autonomous regulation of inhibitory inputs via retrograde signaling”的文章，文中闡述了神經(jīng)網(wǎng)絡(luò)電活動增強(qiáng)快速調(diào)控抑制性突觸穩(wěn)態(tài)可塑性的分子機(jī)制,，這一研究成果公布在The Journal of Neuroscience雜志封面上,。
發(fā)育中的神經(jīng)網(wǎng)絡(luò)需要兼顧生長與穩(wěn)定這兩種相輔相成的需求。穩(wěn)態(tài)可塑性可通過調(diào)節(jié)興奮性或抑制性突觸傳遞從而維持神經(jīng)網(wǎng)絡(luò)的穩(wěn)定,。已報道的關(guān)于穩(wěn)態(tài)可塑性機(jī)制方面的研究主要集中在其對興奮性突觸傳遞的調(diào)節(jié),，很少關(guān)注其對抑制性突觸的調(diào)控。
研究人員發(fā)現(xiàn),，在體外培養(yǎng)的海馬神經(jīng)元中,，持續(xù)增強(qiáng)神經(jīng)元電活動4小時能夠誘導(dǎo)抑制性突觸傳遞的穩(wěn)態(tài)上調(diào),，且這一過程明顯早于興奮性突觸的變化。抑制性突觸傳遞的穩(wěn)態(tài)調(diào)節(jié)依賴于突觸后神經(jīng)元自身電活動的改變,，是一種自我調(diào)節(jié)方式,。這種調(diào)控通過突觸后神經(jīng)元分泌的腦源性神經(jīng)營養(yǎng)因子（BDNF）逆突觸作用于突觸前的抑制性神經(jīng)末梢，從而增強(qiáng)其自身的抑制性突觸輸入,。重要的是,，對幼年大鼠腹腔注射紅藻氨酸，從而在體增強(qiáng)神經(jīng)電活動,，能夠在海馬CA1區(qū)域的錐體神經(jīng)元中誘導(dǎo)出這種抑制性突觸傳遞的穩(wěn)態(tài)調(diào)控,。這些結(jié)果提示，抑制性突觸傳遞的自治性穩(wěn)態(tài)調(diào)控是神經(jīng)元應(yīng)對網(wǎng)絡(luò)電活動增強(qiáng)的一個快速代償性保護(hù)反應(yīng),。（生物谷Bioon.com）
生物谷推薦原文出處：
The Journal of Neuroscience doi:10.1523/JNEUROSCI.3085-10.2010
Postsynaptic Spiking Homeostatically Induces Cell-Autonomous Regulation of Inhibitory Inputs via Retrograde Signaling
Yi-Rong Peng,1,2 * Si-Yu Zeng,1,2 * He-Ling Song,1 Min-Yin Li,1,2 Maki K. Yamada,3,4 and Xiang Yu1
1Institute of Neuroscience and State Key Laboratory of Neuroscience, Shanghai Institutes for Biological Sciences, Chinese Academy of Sciences, Shanghai 200031, China, 2Graduate School of the Chinese Academy of Sciences, Shanghai 200031, China, 3PRESTO (Precursory Research for Embryonic Science and Technology), Japan Science and Technology Agency, Saitama 332-0012, Japan, and 4Department of Cellular Neurobiology, Graduate School of Medicine, The University of Tokyo, Tokyo 113-0033, Japan
Correspondence should be addressed to Xiang Yu at the above address. Email: [email protected]
Developing neural circuits face the dual challenge of growing in an activity-induced fashion and maintaining stability through homeostatic mechanisms. Compared to our understanding of homeostatic regulation of excitatory synapses, relatively little is known about the mechanism mediating homeostatic plasticity of inhibitory synapses, especially that following activity elevation. Here, we found that elevating neuronal activity in cultured hippocampal neurons for 4 h significantly increased the frequency and amplitude of mIPSCs, before detectable change at excitatory synapses. Consistently, we observed increases in presynaptic and postsynaptic proteins of GABAergic synapses, including GAD65, vGAT, and GABAAR1. By suppressing activity-induced increase of neuronal firing with expression of the inward rectifier potassium channel Kir2.1 in individual neurons, we showed that elevation in postsynaptic spiking activity is required for activity-dependent increase in the frequency and amplitude of mIPSCs. Importantly, directly elevating spiking in individual postsynaptic neurons, by capsaicin activation of overexpressed TRPV1 channels, was sufficient to induce increased mIPSC amplitude and frequency, mimicking the effect of elevated neuronal activity. Downregulating BDNF expression in the postsynaptic neuron or its extracellular scavenging prevented activity-induced increase in mIPSC frequency, consistent with a role of BDNF-dependent retrograde signaling in this process. Finally, elevating activity in vivo by kainate injection increased both mIPSC amplitude and frequency in CA1 pyramidal neurons. Thus, spiking-induced, cell-autonomous upregulation of GABAergic synaptic inputs, through retrograde BDNF signaling, represents an early adaptive response of neural circuits to elevated network activity.
