Program in Neurosciences and Mental Health, The Hospital for Sick Children, and the Department of Physiology and Institute of Medical Sciences, University of Toronto, Toronto, Ont., Canada.
J Psychiatry Neurosci. 2010 Jul;35(4):221-8. doi: 10.1503/jpn.100015.
The goal of my research is to gain insight using rodent models into the fundamental molecular, cellular and systems that make up the base of memory formation. My work focuses on fear memories. Aberrant fear and/or anxiety may be at the heart of many psychiatric disorders. In this article, I review the results of my research group; these results show that particular neurons in the lateral amygdala, a brain region important for fear, are specifically involved in particular fear memories. We started by showing that the transcription factor CREB (cAMP/Ca(2+) response element binding protein) plays a key role in the formation of fear memories. Next, we used viral vectors to overexpress CREB in a subset of lateral amygdala neurons. This not only facilitated fear memory formation but also "drove" the memory into the neurons with relatively increased CREB function. Finally, we showed that selective ablation of the neurons overexpressing CREB in the lateral amygdala selectively erased the fear memory. These findings are the first to show disruption of a specific memory by disrupting select neurons within a distributed network.
我的研究目标是利用啮齿动物模型深入了解构成记忆形成基础的基本分子、细胞和系统。我的工作重点是恐惧记忆。异常的恐惧和/或焦虑可能是许多精神疾病的核心。在这篇文章中,我回顾了我所在研究小组的研究结果;这些结果表明,杏仁外侧核(大脑中对恐惧很重要的一个区域)中的特定神经元特别参与了特定的恐惧记忆。我们首先表明,转录因子 CREB(cAMP/Ca(2+)反应元件结合蛋白)在恐惧记忆的形成中起着关键作用。接下来,我们使用病毒载体在杏仁外侧核的一部分神经元中过表达 CREB。这不仅促进了恐惧记忆的形成,而且还“驱使”记忆进入具有相对增加的 CREB 功能的神经元。最后,我们表明,选择性消融杏仁外侧核中过表达 CREB 的神经元选择性地消除了恐惧记忆。这些发现首次表明,通过破坏分布式网络中的特定神经元,可以破坏特定的记忆。