大腦細(xì)胞如何能既記住新記憶同時(shí)又不忘記舊記憶,?科學(xué)家已找到了這方面的答案,。他們發(fā)現(xiàn),大腦齒狀回區(qū)域中的特異神經(jīng)元在記憶形成中起了明顯作用,,取決于產(chǎn)生神經(jīng)元的神經(jīng)干細(xì)胞是年紀(jì)大還是年輕,。
這項(xiàng)研究將在三月三十日的Cell上,,它將記憶形成分子基礎(chǔ)與新神經(jīng)元產(chǎn)生聯(lián)系起來,這項(xiàng)發(fā)現(xiàn)將揭示治療記憶疾病的新一類藥物靶標(biāo),。
這項(xiàng)發(fā)現(xiàn)也表明,,大腦中年輕神經(jīng)元與年長(zhǎng)神經(jīng)元間的不平衡可能瓦解創(chuàng)傷后精神緊張性(精神)障礙(PTSD)與衰老期間的正常記憶形成。
在這項(xiàng)研究中,,作者測(cè)試了2類記憶過程小鼠。模式分離是大腦區(qū)分相似事件間不同的過程,,如記憶不同口味的馬德琳餅干,。相反,模式完成是用于喚起有限線索基礎(chǔ)上的詳細(xì)內(nèi)容記憶,,比如回想起當(dāng)時(shí)是與誰品味馬德琳餅干,。
模式分離形成不同經(jīng)驗(yàn)基礎(chǔ)上的獨(dú)特的新記憶;模式完成通過檢測(cè)相似來恢復(fù)記憶,。腦損傷或外傷的人可能無法回憶起他們每天都見的人,。PTSD病人不能忘記可怕的事件。受損的模式分離由于失去年輕神經(jīng)元可能有利于模式完成,,這可能突出在PTSD病人中觀察到的復(fù)發(fā)的可怕記憶回憶,。神經(jīng)科學(xué)家一直認(rèn)為這兩個(gè)對(duì)立且潛在競(jìng)爭(zhēng)的過程出現(xiàn)在不同神經(jīng)回路中。齒狀回,,是中樞神經(jīng)系統(tǒng)內(nèi)一個(gè)具顯著可塑性的結(jié)構(gòu),,它在抑郁、癲癇到可怕腦外傷中的作用被認(rèn)為涉及到分離模式和模式完成的CA3區(qū)域,。相反,,麻省理工學(xué)院研究人員發(fā)現(xiàn)齒狀回神經(jīng)元可能執(zhí)行模式分離或模式完成取決于它們細(xì)胞的年齡。
麻省理工學(xué)院研究人員在小鼠上評(píng)估了模式分離,,這些小鼠學(xué)會(huì)區(qū)分兩個(gè)相似但不同的房間:一間安全,,另一間與不愉快的腳電擊相關(guān)。為了測(cè)試它們的模式完成能力,,給老鼠逃離它們以前學(xué)會(huì)交涉的迷宮的有限線索,。將正常小鼠與缺少年輕神經(jīng)元或年老神經(jīng)元小鼠相比。小鼠表現(xiàn)出模式完成或分離的缺陷,,取決于哪一組神經(jīng)元被刪除,。
神經(jīng)電路遺傳學(xué)RIKEN-MIT中心(RIKEN-MIT Center for Neural Circuit Genetics),霍華德 · 休斯醫(yī)學(xué)研究所(Howard Hughes Medical Institute)大冢馬里蘭研究院(Otsuka Maryland Research Institute), Picower基金會(huì)(Picower Foundation)和NIH支持此項(xiàng)研究,。(生物谷bioon.com)
doi:10.1016/j.cell.2012.01.046
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Young Dentate Granule Cells Mediate Pattern Separation, whereas Old Granule Cells Facilitate Pattern Completion
Toshiaki Nakashiba, Jesse D. Cushman, Kenneth A. Pelkey, Sophie Renaudineau, Derek L. Buhl, Thomas J. McHugh, Vanessa Rodriguez Barrera, Ramesh Chittajallu, Keisuke S. Iwamoto, Chris J. McBain, Michael S. Fanselow, Susumu Tonegawa
dult-born granule cells (GCs), a minor population of cells in the hippocampal dentate gyrus, are highly active during the first few weeks after functional integration into the neuronal network, distinguishing them from less active, older adult-born GCs and the major population of dentate GCs generated developmentally. To ascertain whether young and old GCs perform distinct memory functions, we created a transgenic mouse in which output of old GCs was specifically inhibited while leaving a substantial portion of young GCs intact. These mice exhibited enhanced or normal pattern separation between similar contexts, which was reduced following ablation of young GCs. Furthermore, these mutant mice exhibited deficits in rapid pattern completion. Therefore, pattern separation requires adult-born young GCs but not old GCs, and older GCs contribute to the rapid recall by pattern completion. Our data suggest that as adult-born GCs age, their function switches from pattern separation to rapid pattern completion.