生物谷：我们的经历——例如我们看到的、听到的东西以及所做的事情——都能引起大脑中神经元之间连接的强度的长期改变，并且这些持久的改变是我们大脑编译信息的方式。根据发表在本周的Neuron上的文章，来自Johns Hopkins大学的科学家们发现了一种记忆存储的生物化学机制，而这一机制可能和上瘾行为有关。
在这之前，科学家们认为神经元之间连接的长期改变只包含一种快速的大脑电信号形式，它大约只持续百分之一秒时间。但是现在，神经科学教授David Linden博士和他的同事发现了另外一种比之前认为的慢得多的电信号形式，这种电信号持续时间大约为一秒，它也能通过经历而得到长期的改变。
科学家们通过对老鼠的大脑切片施加一个短的电刺激来激发自然的大脑运动，然后测量通过脑部神经细胞的电流强度。在重复电流刺激之后，慢的神经信号强度出现了大幅度的下降，并且这种下降在电流刺激中断之后的30分钟内仍然保持在比较低的强度范围内。
小组发现这些慢速神经信号是通过一种被称为mGluR1的神经细胞受体产生的，在之前的研究中科学家曾发现该受体与上瘾和癫痫症有关。Linden说：“这些疾病都包含了神经连接功能的长期变化，因此除了进一步进行记忆存储的基础研究外，设计用于改变mGluR1的药物将可能用于治疗成瘾、癫痫和其它记忆相关的疾病。”（援引教育部科技发展中心网）
原始出处:
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
sangjkim@snu.ac.kr
Corresponding author
David J. Linden
dlinden@jhmi.edu
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.
