GABA轉(zhuǎn)運體通過控制突觸間隙的GABA濃度及其受體GABA（A）介導(dǎo)的抑制性效應(yīng),，調(diào)節(jié)海馬腦區(qū)theta節(jié)律刺激（TBS）誘導(dǎo)的LTP以及theta振蕩
12月16日，美國《神經(jīng)科學(xué)雜志》（Journal of Neuroscience）在線發(fā)表了中國科學(xué)院上海生命科學(xué)研究院神經(jīng)科學(xué)研究所徐天樂研究組的最新研究成果――“GABA Transporter-1 Activity Modulates Hippocampal Theta Oscillation and Theta Burst Stimulation-Induced Long-Term Potentiation”,。大腦的網(wǎng)絡(luò)振蕩活動和突觸可塑性被認(rèn)為與學(xué)習(xí)記憶的形成密切相關(guān),。近年來,，腦內(nèi)最主要的抑制性神經(jīng)遞質(zhì)GABA以及GABA能中間神經(jīng)元在神經(jīng)網(wǎng)絡(luò)活動中的作用一直是神經(jīng)科學(xué)熱點課題之一。GABA轉(zhuǎn)運體主要負(fù)責(zé)突觸釋放的GABA的重攝取,，進(jìn)而控制細(xì)胞外GABA的濃度,。幾年前同濟(jì)大學(xué)費儉研究組成功制備出了1型GABA轉(zhuǎn)運體（GAT1）基因敲除小鼠，該動物模型為研究腦內(nèi)GABA及其受體在學(xué)習(xí)記憶等腦認(rèn)知活動中的作用提供了一個重要工具,。徐天樂研究員指導(dǎo)的博士后龔能及合作者利用GAT1敲除小鼠和GAT1特異性抑制劑No711,，發(fā)現(xiàn)在小鼠海馬CA1區(qū)，GABA通過作用于其受體GABA(A)調(diào)節(jié)theta節(jié)律刺激（theta burst stimulation,，TBS）誘導(dǎo)的長時程增強(qiáng)（LTP）形式的突觸可塑性。這種theta節(jié)律性的刺激模式來源于腦電中觀察到的theta振蕩（theta oscillation）。通過在活體動物觀察GAT1敲除后海馬區(qū)的theta振蕩,，發(fā)現(xiàn)GAT1敲除顯著降低theta節(jié)律的振蕩頻率,。在觀察到網(wǎng)絡(luò)振蕩和可塑性發(fā)生改變的同時，還發(fā)現(xiàn)GAT1敲除小鼠海馬依賴的空間學(xué)習(xí)記憶能力明顯受損,。這項研究進(jìn)一步證實了GABA及其受體在節(jié)律性神經(jīng)網(wǎng)絡(luò)活動（特別是theta振蕩）,，突觸可塑性以及學(xué)習(xí)記憶等腦認(rèn)知行為中重要作用。同時,，由于抑制GABA(A)受體可逆轉(zhuǎn)GAT1敲除小鼠受損的海馬突觸可塑性,，這一研究也為開發(fā)針對學(xué)習(xí)記憶受損的腦認(rèn)知相關(guān)疾病的有效藥物提供了新線索。（生物谷Bioon.com）
生物谷推薦原始出處：
The Journal of Neuroscience, December 16, 2009, 29(50):15836-15845; doi:10.1523/JNEUROSCI.4643-09.2009
GABA Transporter-1 Activity Modulates Hippocampal Theta Oscillation and Theta Burst Stimulation-Induced Long-Term Potentiation
Neng Gong,1 Yong Li,2 Guo-Qiang Cai,3 Rui-Fang Niu,4 Qi Fang,1,5 Kun Wu,1,6 Zhong Chen,5 Long-Nian Lin,4 Lin Xu,1,6 Jian Fei,3 and Tian-Le Xu1
1Institute of Neuroscience and State Key Laboratory of Neuroscience, Shanghai Institutes for Biological Sciences, Chinese Academy of Sciences, Shanghai 200031, China, 2Department of Neurobiology, Institutes of Medical Sciences, Shanghai Jiaotong University, Shanghai 200025, China, 3School of Life Science and Technology, Tongji University, Shanghai 200092, China, 4Shanghai Institute of Brain Functional Genomics, East China Normal University, Shanghai 200062, 5College of Pharmaceutical Sciences, Zhejiang University, Hangzhou 310058, China, and 6Kunming Institute of Zoology, Chinese Academy of Sciences, Kunming 650223, China
The network oscillation and synaptic plasticity are known to be regulated by GABAergic inhibition, but how they are affected by changes in the GABA transporter activity remains unclear. Here we show that in the CA1 region of mouse hippocampus, pharmacological blockade or genetic deletion of GABA transporter-1 (GAT1) specifically impaired long-term potentiation (LTP) induced by theta burst stimulation, but had no effect on LTP induced by high-frequency stimulation or long-term depression induced by low-frequency stimulation. The extent of LTP impairment depended on the precise burst frequency, with significant impairment at 3–7 Hz that correlated with the time course of elevated GABAergic inhibition caused by GAT1 disruption. Furthermore, in vivo electrophysiological recordings showed that GAT1 gene deletion reduced the frequency of hippocampal theta oscillation. Moreover, behavioral studies showed that GAT1 knock-out mice also exhibited impaired hippocampus-dependent learning and memory. Together, these results have highlighted the important link between GABAergic inhibition and hippocampal theta oscillation, both of which are critical for synaptic plasticity and learning behaviors.
