NR2B是一種與學(xué)習(xí)記憶相關(guān)的基因,。一只具有較強(qiáng)的學(xué)習(xí)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(xué)論文發(fā)表在最新一期的國(guó)際權(quán)威期刊《公共科學(xué)圖書館·綜合》（PLoS ONE）雜志上。
由華東師大腦功能基因組學(xué)教育部及上海市重點(diǎn)實(shí)驗(yàn)室曹曉華教授,、西雙版納靈長(zhǎng)類模式動(dòng)物中心以及美國(guó)喬治亞醫(yī)科大學(xué)大腦與行為研究所所長(zhǎng)錢卓教授組成的聯(lián)合團(tuán)隊(duì),，共同構(gòu)建了這只轉(zhuǎn)基因的“聰明大鼠”，并進(jìn)一步證實(shí)了“NR2B基因”在大鼠的學(xué)習(xí)記憶功能中具有重要作用,?？茖W(xué)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(xué)習(xí)記憶作用的“NR2B基因”成功地在“哈卜杰”的前腦高量表達(dá),，并從分子,、細(xì)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(duì)“哈卜杰”進(jìn)行了多種行為測(cè)試,，以檢測(cè)它在學(xué)習(xí)記憶方面的功能,。水迷宮是大鼠學(xué)習(xí)記憶功能的其中一項(xiàng)實(shí)驗(yàn)?？蒲腥藛T在一個(gè)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(gè)直徑15厘米的平臺(tái),，并在水中添加白色食用染料,，將這個(gè)平臺(tái)隱藏起來(lái)，結(jié)果“哈卜杰”很快就到了水下隱藏的平臺(tái),，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(gè)平臺(tái)撤除,，“哈卜杰”潛入水后,，很快就找到了平臺(tái)原先所在的區(qū)域，在那里停留的時(shí)間也比非轉(zhuǎn)基因的“兄弟姐妹”長(zhǎng)得多,，這表明它學(xué)得快,、記得牢。
此外,，“哈卜杰”在新異物體識(shí)別和T－型迷宮的測(cè)試中,，也表現(xiàn)出學(xué)習(xí)記憶能力強(qiáng)的高智力。
20世紀(jì)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(xué)習(xí)記憶中的作用。隨后,，他領(lǐng)導(dǎo)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(jìn)一步證明了NMDA受體的NR2B是小鼠學(xué)習(xí)記憶的關(guān)鍵分子開關(guān),。
與小鼠相比,，大鼠是生物醫(yī)學(xué)研究比較理想的動(dòng)物模型。因?yàn)橛嘘P(guān)大鼠生理,、藥理和行為學(xué)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(jìn)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(jī)制,。
與此同時(shí),，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(rèn)為,，此項(xiàng)工作推動(dòng)了腦科學(xué)的發(fā)展，也為改善人腦的學(xué)習(xí)記憶功能提供了理論指導(dǎo)依據(jù),。
據(jù)悉,，研究工作得到了科技部973項(xiàng)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(diǎn)關(guān)注：2010廣州國(guó)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.
