NR2B是一種與學習記憶相關(guān)的基因。一只具有較強的學習和記憶功能的NR2B轉(zhuǎn)基因“聰明大鼠”誕生了。這一研究的相關(guān)科學論文發(fā)表在最新一期的國際權(quán)威期刊《公共科學圖書館·綜合》（PLoS ONE）雜志上,。
由華東師大腦功能基因組學教育部及上海市重點實驗室曹曉華教授、西雙版納靈長類模式動物中心以及美國喬治亞醫(yī)科大學大腦與行為研究所所長錢卓教授組成的聯(lián)合團隊,，共同構(gòu)建了這只轉(zhuǎn)基因的“聰明大鼠”,，并進一步證實了“NR2B基因”在大鼠的學習記憶功能中具有重要作用?？茖W家根據(jù)目前流行的兒童圖話故事《聰明鼠哈卜杰環(huán)游世界》,，將這只黑白相間的聰明大鼠取名為“哈卜杰”（Hobbie－J）。
據(jù)介紹,，科研人員利用腦區(qū)特異性的轉(zhuǎn)基因技術(shù),，將具有學習記憶作用的“NR2B基因”成功地在“哈卜杰”的前腦高量表達，并從分子、細胞突觸和整體行為不同的層次分析了NR2B轉(zhuǎn)基因大鼠的表型,。
科研人員對“哈卜杰”進行了多種行為測試,，以檢測它在學習記憶方面的功能。水迷宮是大鼠學習記憶功能的其中一項實驗,?？蒲腥藛T在一個直徑150厘米、高50厘米,、水深30厘米的圓形水池內(nèi),，在水下約2厘米處放置一個直徑15厘米的平臺，并在水中添加白色食用染料,，將這個平臺隱藏起來,，結(jié)果“哈卜杰”很快就到了水下隱藏的平臺，比同窩的非轉(zhuǎn)基因的“兄弟姐妹”快得多,。此后,，科研人員將這個平臺撤除，“哈卜杰”潛入水后,，很快就找到了平臺原先所在的區(qū)域,，在那里停留的時間也比非轉(zhuǎn)基因的“兄弟姐妹”長得多，這表明它學得快,、記得牢,。
此外，“哈卜杰”在新異物體識別和T－型迷宮的測試中,，也表現(xiàn)出學習記憶能力強的高智力,。
20世紀90年代，華東師大錢卓教授曾利用特異性的基因剔除技術(shù),，證明了NMDA受體在學習記憶中的作用,。隨后，他領(lǐng)導的研究小組利用區(qū)域特異性的轉(zhuǎn)基因技術(shù),，創(chuàng)建了“聰明小鼠”,，進一步證明了NMDA受體的NR2B是小鼠學習記憶的關(guān)鍵分子開關(guān)。
與小鼠相比,，大鼠是生物醫(yī)學研究比較理想的動物模型,。因為有關(guān)大鼠生理、藥理和行為學方面已積累了大量的研究歷史資料,；而且大鼠的身體大（300克－500克,，小鼠僅為20克－35克）、腦體積也大,，更適于進行高密度群體神經(jīng)元在體記錄,，有利于從神經(jīng)元網(wǎng)絡(luò)水平研究腦功能的機制,。
與此同時，人類的NR2B基因與大鼠,、小鼠的NR2B基因非常相似,。業(yè)內(nèi)專家認為，此項工作推動了腦科學的發(fā)展,，也為改善人腦的學習記憶功能提供了理論指導依據(jù),。
據(jù)悉，研究工作得到了科技部973項目,、教育部,、上海市科委、云南省科技廳共同支持,。（生物谷Bioon.com）
熱點關(guān)注：2010廣州國際小型豬論壇
生物谷推薦原始出處：
PLoS ONE 4(10): e7486. doi:10.1371/journal.pone.0007486
Genetic Enhancement of Memory and Long-Term Potentiation but Not CA1 Long-Term Depression in NR2B Transgenic Rats
Deheng Wang1,2#, Zhenzhong Cui2#, Qingwen Zeng1, Hui Kuang1,3, L. Phillip Wang2,3, Joe Z. Tsien2*, Xiaohua Cao1*
1 Shanghai Institute of Brain Functional Genomics, the Key Laboratories of MOE and STCSM and College of Life Sciences, East China Normal University, Shanghai, China, 2 Brain and Behavior Discovery Institute and Department of Neurology, School of Medicine, Medical College of Georgia, Augusta, Georgia, United States of America, 3 Yunnan Banna Primate Model Research Center, Xishuang-Banna, Yunnan, China
One major theory in learning and memory posits that the NR2B gene is a universal genetic factor that acts as rate-limiting molecule in controlling the optimal NMDA receptor's coincidence-detection property and subsequent learning and memory function across multiple animal species. If so, can memory function be enhanced via transgenic overexpression of NR2B in another species other than the previously reported mouse species? To examine these crucial issues, we generated transgenic rats in which NR2B is overexpressed in the cortex and hippocampus and investigated the role of NR2B gene in NMDA receptor-mediated synaptic plasticity and memory functions by combining electrophysiological technique with behavioral measurements. We found that overexpression of the NR2B subunit had no effect on CA1-LTD, but rather resulted in enhanced CA1-LTP and improved memory performances in novel object recognition test, spatial water maze, and delayed-to-nonmatch working memory test. Our slices recordings using NR2A- and NR2B-selective antagonists further demonstrate that the larger LTP in transgenic hippocampal slices was due to contribution from the increased NR2B-containing NMDARs. Therefore, our genetic experiments suggest that NR2B at CA1 synapses is not designated as a rate-limiting factor for the induction of long-term synaptic depression, but rather plays a crucial role in initiating the synaptic potentiation. Moreover, our studies provide strong evidence that the NR2B subunit represents a universal rate-limiting molecule for gating NMDA receptor's optimal coincidence-detection property and for enhancing memory function in adulthood across multiple mammalian species.
