神經(jīng)細(xì)胞之間通過(guò)特異的通訊結(jié)構(gòu)——“突觸”——形成功能性神經(jīng)環(huán)路來(lái)傳遞和存儲(chǔ)信息。突觸在神經(jīng)細(xì)胞持續(xù)活動(dòng)影響下可發(fā)生特異性的結(jié)構(gòu)和功能變化,，這稱之為“突觸可塑性”。它在神經(jīng)系統(tǒng)發(fā)育和學(xué)習(xí)記憶中起著至關(guān)重要的作用,。在神經(jīng)環(huán)路組成中，釋放神經(jīng)遞質(zhì)谷氨酸和γ—氨基丁酸（GABA）的神經(jīng)元分別傳遞興奮性和抑制性信息,。其中占總細(xì)胞少數(shù)（約10% —20%）的GABA能神經(jīng)元卻對(duì)神經(jīng)環(huán)路的功能平衡,，復(fù)雜性以及計(jì)算建構(gòu)起著關(guān)鍵作用，其突觸傳遞在神經(jīng)信息的編碼,、分選和傳遞中發(fā)揮重要作用,。 然而，對(duì)這些少數(shù)的GABA能突觸的可塑性發(fā)生機(jī)理卻知之甚少,。
2008年10月26日《自然—神經(jīng)學(xué)》（Nature Neuroscience）在線提前發(fā)表了中科院神經(jīng)所博士研究生徐春和趙漫夏完成的關(guān)于GABA能突觸可塑性的發(fā)生模式和機(jī)理的重要研究工作,。該項(xiàng)工作是在蒲慕明研究員和章曉輝研究員指導(dǎo)下完成。在本項(xiàng)工作當(dāng)中,，作者在急性分離的大鼠海馬腦片中進(jìn)行了系統(tǒng)的電生理研究,，發(fā)現(xiàn)發(fā)育早期GABA能突觸的可塑性表現(xiàn)出神經(jīng)元活動(dòng)頻率依賴的特性——高頻率神經(jīng)元相關(guān)活動(dòng)引起突觸效能的長(zhǎng)時(shí)程增強(qiáng)（LTP）；而低頻活動(dòng)則引起長(zhǎng)時(shí)程減弱（LTD）,。并且,，GABA能突觸傳遞中的GABAB受體信號(hào)在高頻活動(dòng)誘導(dǎo)的長(zhǎng)時(shí)程增強(qiáng)（LTP）中起著門控機(jī)制，能調(diào)制此突觸可塑性的頻率依賴性,。作者通過(guò)進(jìn)一步的研究表明,，高頻神經(jīng)元活動(dòng)通過(guò)增強(qiáng)了突觸后細(xì)胞胞內(nèi)CaMKII激酶活性和細(xì)胞膜上Cl—轉(zhuǎn)運(yùn)體活動(dòng)，進(jìn)而改變胞內(nèi)Cl—濃度而產(chǎn)生LTP,。GABA突觸在發(fā)育早期介導(dǎo)興奮性的傳遞,，對(duì)神經(jīng)網(wǎng)絡(luò)的形成和重塑起著關(guān)鍵作用。因此,，這項(xiàng)研究工作揭示了發(fā)育中GABA能突觸可塑性的發(fā)生模式和細(xì)胞分子機(jī)制,，闡明了神經(jīng)環(huán)路建立中GABA能突觸連接的自我精細(xì)修整（refinement）的工作方式。
該項(xiàng)研究工作受科技部973項(xiàng)目（2006CB806600 和2006CB943900）資助,。（生物谷Bioon.com）
生物谷推薦原始出處：
Nature Neuroscience,，doi:10.1038/nn.2215，Chun Xu, Man-xia Zhao, Mu-ming Poo, Xiao-hui Zhang
GABAB receptor activation mediates frequency-dependent plasticity of developing GABAergic synapses
Chun Xu1, Man-xia Zhao1, Mu-ming Poo1,2 & Xiao-hui Zhang1
AbstractActivity-induced long-term modification of glutamatergic synapses depends on the frequency of synaptic activation. We found that long-term modification of developing rat hippocampal GABAergic synapses that was induced by repetitive coincident pre- and postsynaptic spiking was also frequency dependent. Spiking at 20–50 Hz resulted in synaptic potentiation, whereas spiking at 5 Hz led to synaptic depression. The potentiation was abolished by blocking GABAB receptors (GABABRs), whereas the depression was independent of GABABR activation and could be converted to potentiation by elevating GABABR activity. The potentiation could be attributed to a local postsynaptic increase in Na+/K+/2Cl- co-transporter activity near activated synapses. The activity of postsynaptic Ca2+/calmodulin-dependent protein kinase II was necessary for long-term potentiation of these developing GABAergic synapses and its phosphorylation at Thr286 could be enhanced by activating GABABRs with baclofen. Together with our finding that activation of GABABRs is frequency dependent, these results indicate that postsynaptic GABABR activation mediates frequency-dependent potentiation of developing GABAergic synapses.
1 Institute of Neuroscience, State Key Laboratory of Neuroscience, Shanghai Institutes for Biological Sciences, Chinese Academy of Sciences, 320 Yue-Yang Road Shanghai 200031, China.
2 Division of Neurobiology, Department of Molecular & Cell Biology, Helen Wills Neuroscience Institute, University of California Berkeley, 221 LSA, Berkeley, California 94720, USA.
