5-羥色胺是一種傳遞神經(jīng)信號的物質(zhì),，最新研究發(fā)現(xiàn)無法產(chǎn)生神經(jīng)遞質(zhì)5-羥色胺的小鼠的焦慮程度較正常小鼠更低,，但是保持恐懼記憶的時間更長,。5-羥色胺是與一大批行為有關(guān)的重要的信號傳導(dǎo)分子,，但是和抑郁,、焦慮以及創(chuàng)傷后應(yīng)激障礙（PSTD）特別有關(guān),，所有這些都常常與學(xué)習(xí)和記憶困難有聯(lián)系,。中科院神經(jīng)所丁玉強(qiáng)及其同事此前開發(fā)了一種遺傳方法,，用于從小鼠的腦中移除制造5-羥色胺的神經(jīng)元，同時完整地保留其它神經(jīng)元——其中許多擁有5-羥色胺的受體,。
研究人員通過比較缺乏5-羥色胺的小鼠和對照組的小鼠,，實驗把小鼠置于被設(shè)計用于引發(fā)焦慮或恐懼的環(huán)境中。缺乏5-羥色胺的小鼠在一個高架迷宮的開口部分游蕩的時候比對照組小鼠更加放松,，這提示它們焦慮程度更低,。在小鼠被置于特制的籠子里接受腳部電擊的實驗中，缺乏5-羥色胺的小鼠似乎比對照組小鼠保持對這個籠子的不愉快的記憶時間更長,，而且更不容易忘記被電擊,。這組科學(xué)家報告說，向缺乏5-羥色胺的小鼠腦中直接注射5-羥色胺似乎可以消除這種顯示小鼠因為它們的經(jīng)歷而產(chǎn)生壓力的行為,。（生物谷Bioon.com）
生物谷推薦原始出處：
PNAS published ahead of print August 11, 2008, doi:10.1073/pnas.0801329105
Enhanced contextual fear memory in central serotonin-deficient mice
Jin-Xia Dai*,†, Hui-Li Han†,‡, Meng Tian‡, Jun Cao‡, Jian-Bo Xiu*, Ning-Ning Song*, Ying Huang*, Tian-Le Xu*, Yu-Qiang Ding*,§, and Lin Xu‡,§,¶
+Author Affiliations
*Institute of Neuroscience and State Key Laboratory of Neuroscience, Chinese Academy of Sciences, Shanghai 200031, China;
‡Key Laboratory of Animal Models and Human Disease Mechanisms, Kunming Institute of Zoology, Chinese Academy of Sciences, Kunming 650223, China; and
¶Mental Health Institute, Second Xiangya Hospital of Central South University, Changsha 410011, China
↵†J.-X.D and H.-L.H contributed equally to this work.
Edited by Tomas Hökfelt, Karolinska Institutet, Stockholm, Sweden, and approved June 6, 2008 (received for review February 12, 2008)
Abstract
Central serotonin (5-HT) dysregulation contributes to the susceptibility for mental disorders, including depression, anxiety, and posttraumatic stress disorder, and learning and memory deficits. We report that the formation of hippocampus-dependent spatial memory is compromised, but the acquisition and retrieval of contextual fear memory are enhanced, in central 5-HT-deficient mice. Genetic deletion of serotonin in the brain was achieved by inactivating Lmx1b selectively in the raphe nuclei of the brainstem, resulting in a near-complete loss of 5-HT throughout the brain. BIOONThese 5-HT-deficient mice exhibited no gross abnormality in brain structures and had normal locomotor activity. Spatial learning in the Morris water maze was unaffected, but the retrieval of spatial memory was impaired. In contrast, contextual fear learning and memory induced by foot-shock conditioning was markedly enhanced, but this enhancement could be prevented by intracerebroventricular administration of 5-HT. Foot shock impaired long-term potentiation and facilitated long-term depression in hippocampal slices in WT mice but had no effect in 5-HT-deficient mice. Furthermore, bath application of 5-HT in 5-HT-deficient mice restored foot shock-induced alterations of hippocampal synaptic plasticity. Thus, central 5-HT regulates hippocampus-dependent contextual fear memory, and 5-HT modulation of hippocampal synaptic plasticity may be the underlying mechanism. The enhanced fear memory in 5-HT-deficient mice supports the notion that 5-HT deficiency confers susceptibility to posttraumatic stress disorder in humans.
