生物谷：我們的經(jīng)歷——例如我們看到的、聽到的東西以及所做的事情——都能引起大腦中神經(jīng)元之間連接的強度的長期改變,，并且這些持久的改變是我們大腦編譯信息的方式,。根據(jù)發(fā)表在本周的Neuron上的文章，來自Johns Hopkins大學(xué)的科學(xué)家們發(fā)現(xiàn)了一種記憶存儲的生物化學(xué)機制,，而這一機制可能和上癮行為有關(guān),。
在這之前，科學(xué)家們認為神經(jīng)元之間連接的長期改變只包含一種快速的大腦電信號形式,，它大約只持續(xù)百分之一秒時間,。但是現(xiàn)在，神經(jīng)科學(xué)教授David Linden博士和他的同事發(fā)現(xiàn)了另外一種比之前認為的慢得多的電信號形式,，這種電信號持續(xù)時間大約為一秒,，它也能通過經(jīng)歷而得到長期的改變。
科學(xué)家們通過對老鼠的大腦切片施加一個短的電刺激來激發(fā)自然的大腦運動,，然后測量通過腦部神經(jīng)細胞的電流強度,。在重復(fù)電流刺激之后，慢的神經(jīng)信號強度出現(xiàn)了大幅度的下降,，并且這種下降在電流刺激中斷之后的30分鐘內(nèi)仍然保持在比較低的強度范圍內(nèi),。
小組發(fā)現(xiàn)這些慢速神經(jīng)信號是通過一種被稱為mGluR1的神經(jīng)細胞受體產(chǎn)生的，在之前的研究中科學(xué)家曾發(fā)現(xiàn)該受體與上癮和癲癇癥有關(guān),。Linden說：“這些疾病都包含了神經(jīng)連接功能的長期變化,，因此除了進一步進行記憶存儲的基礎(chǔ)研究外，設(shè)計用于改變mGluR1的藥物將可能用于治療成癮,、癲癇和其它記憶相關(guān)的疾病,。”（援引教育部科技發(fā)展中心網(wǎng)）
原始出處:
Copyright © 2007 Cell Press. All rights reserved.
Neuron, Vol 55, 277-287, 19 July 2007
Article
Long-Term Depression of mGluR1 Signaling
Yunju Jin,1 Sang Jeong Kim,1, Jun Kim,1 Paul F. Worley,2 and David J. Linden2,
1 Department of Physiology, Seoul National University College of Medicine and Neuroscience Research Institute Medical Research Center, Korea
2 Department of Neuroscience, Johns Hopkins University School of Medicine, Baltimore, MD 21205, USA
Corresponding author
Sang Jeong Kim
[email protected]
Corresponding author
David J. Linden
[email protected]
Summary
Glutamate produces both fast excitation through activation of ionotropic receptors and slower actions through metabotropic receptors (mGluRs). To date, ionotropic but not metabotropic neurotransmission has been shown to undergo long-term synaptic potentiation and depression. Burst stimulation of parallel fibers releases glutamate, which activates perisynaptic mGluR1 in the dendritic spines of cerebellar Purkinje cells. Here, we show that the mGluR1-dependent slow EPSC and its coincident Ca transient were selectively and persistently depressed by repeated climbing fiber-evoked depolarization of Purkinje cells in brain slices. LTD(mGluR1) was also observed when slow synaptic current was evoked by exogenous application of a group I mGluR agonist, implying a postsynaptic expression mechanism. Ca imaging further revealed that LTD(mGluR1) was expressed as coincident attenuation of both limbs of mGluR1 signaling: the slow EPSC and PLC/IP3-mediated dendritic Ca mobilization. Thus, different patterns of neural activity can evoke LTD of either fast ionotropic or slow mGluR1-mediated synaptic signaling.
