生物谷：心患有焦慮癥的人常常將不明確的環(huán)境視作威脅，最近,，來自歐洲分子生物學實驗室（EMBL）的科學家發(fā)現(xiàn)了老鼠中焦慮的分子學基礎,。在最新的Nature Neuroscience中,，他們報導了一種血清胺（serotonin）受體和大腦海馬體中一種神經(jīng)回路在產(chǎn)生這種恐懼反應過程中起到了關鍵作用。??
老鼠能記住某些暗示,，例如在一個聲音之后常常跟著電擊,，因此它們會將這兩者聯(lián)系起來，即使在沒有電擊的時候,，老鼠聽到聲音也會害怕,。但在現(xiàn)實生活中情況沒有這么明顯。正常老鼠對于模糊暗示的恐懼程度要小于明確的威脅暗示,。??
由EMBL的Cornelius Gross領導的研究小組發(fā)現(xiàn)對于模糊的刺激反應需要血清胺的一種特殊受體分子,，血清胺是很多大腦細胞交流的信號,。缺少血清胺受體1A的老鼠對于處理模糊刺激存在問題，因此對它們會做出完全的威脅反應,。其中原因在于大腦細胞錯誤的聯(lián)系,。血清胺信號在大腦發(fā)育中非常重要，如果沒有1A,，大腦聯(lián)系會存在缺陷,，并且將影響老鼠的行為。??
利用一種關閉特定大腦細胞神經(jīng)活動的技術,，Gross和同事發(fā)現(xiàn)海馬體的一個特殊部位對于正確處理模糊刺激很重要,。海馬體是負責學習和記憶的區(qū)域，但是研究顯示它在評估信息方面也起著重要作用,。??
以上對于血清胺受體1A和海馬體在恐懼行為中作用的發(fā)現(xiàn)將有助于了解焦慮的神經(jīng)基礎,，并帶來新的治療手段。（引自教育部科技發(fā)展中）
原始出處:
Nature Neuroscience
Published online: 3 June 2007; | doi:10.1038/nn1919
Suppression of conditioning to ambiguous cues by pharmacogenetic inhibition of the dentate gyrus
Theodoros Tsetsenis1, Xiao-Hong Ma2, Luisa Lo Iacono1, Sheryl G Beck2 & Cornelius Gross1
1 European Molecular Biology Laboratory (EMBL), Mouse Biology Unit, Via Ramarini 32, 00015 Monterotondo, Italy.
2 Children's Hospital of Philadelphia, 3615 Civic Center Blvd., Philadelphia, Pennsylvania 19104, USA.
Serotonin receptor 1A knockout (Htr1aKO) mice show increased anxiety-related behavior in tests measuring innate avoidance. Here we demonstrate that Htr1aKO mice show enhanced fear conditioning to ambiguous conditioned stimuli, a hallmark of human anxiety. To examine the involvement of specific forebrain circuits in this phenotype, we developed a pharmacogenetic technique for the rapid tissue- and cell type–specific silencing of neural activity in vivo. Inhibition of neurons in the central nucleus of the amygdala suppressed conditioned responses to both ambiguous and nonambiguous cues. In contrast, inhibition of hippocampal dentate gyrus granule cells selectively suppressed conditioned responses to ambiguous cues and reversed the knockout phenotype. These data demonstrate that Htr1aKO mice have a bias in the processing of threatening cues that is moderated by hippocampal mossy-fiber circuits, and suggest that the hippocampus is important in the response to ambiguous aversive stimuli
