Applying in vitro recording techniques to extinction of conditioned fear

应用体外记录技术消除条件性恐惧

• 批准号: 0842159
• 负责人: James Porter
• 金额: $ 40万
• 依托单位: Ponce School of Medicine
• 依托单位国家: 美国
• 项目类别: Continuing Grant
• 财政年份: 2009
• 资助国家: 美国
• 起止时间: 2009-06-01 至 2013-05-31
• 项目状态: 已结题
• 来源: https://www.nsf.gov/awardsearch/showAward?AWD_ID=0842159&HistoricalAwards=false
• 关键词: Applying; vitro; recording; techniques; extinction

The ability to adapt behavioral response to environmental cues is critical for survival and requires learning to associate a given cue with a given consequence so that an appropriate response can be made. The extinction of Pavlovian fear conditioning is a commonly used model of associative learning in which an animal must learn that a neutral stimulus (tone) that was previously paired with an aversive stimulus (footshock) no longer predicts the aversive stimulus. Rather than erase fear memory, extinction is thought to form a new memory that signals safety. Activity in the medial prefrontal cortex (mPFC) is critical for the recall of fear extinction memory. In this project investigators from two Puerto Rican institutions will combine their expertise in slice recording and neural systems of fear learning to examine the intrinsic cellular mechanisms that mediate the extinction-induced enhancement of mPFC activity. The investigators will use a multidisciplinary approach combining in vitro patch-clamp electrophysiology, histology, in vivo single neuron recordings, behavioral training, and in vitro and in vivo neuropharmacology.The investigators expect to demonstrate that extinction training enhances the intrinsic excitability of mPFC neurons, that metabotropic glutamate receptor subtype 5 (mGluR5) controls the intrinsic excitability in mPFC neurons, and that the stimulation of mGluR5 receptors in vivo augments the recall of extinction memory. The results of this study will provide important groundwork for understanding how extinction memory is encoded at the level of single neurons.This project creates a unique opportunity for Puerto Rican graduate and undergraduate students to learn a multidisciplinary and collaborative approach to science. Students in both laboratories will be involved in the project and will present their results at the Society for Neuroscience Annual Meetings.

使行为反应适应环境线索的能力对于生存至关重要，并且需要学习将给定线索与给定后果联系起来，以便做出适当的反应。巴甫洛夫恐惧条件反射的消失是一种常用的联想学习模型，其中动物必须学习先前与厌恶刺激（电击脚）配对的中性刺激（音调）不再预测厌恶刺激。灭绝并不是消除恐惧记忆，而是形成一个新的记忆，标志着安全。内侧前额叶皮层（mPFC）的活动对于恐惧消退记忆的回忆至关重要。在这个项目中，来自两个波多黎各机构的研究人员将联合收割机结合他们在切片记录和恐惧学习的神经系统方面的专业知识，以研究介导预防诱导的mPFC活性增强的内在细胞机制。研究人员将采用多学科方法，结合体外膜片钳电生理学、组织学、体内单神经元记录、行为训练以及体外和体内神经药理学。研究人员希望证明，消退训练增强mPFC神经元的内在兴奋性，代谢型谷氨酸受体亚型5（mGluR5）控制mPFC神经元的内在兴奋性，并且体内mGluR5受体的刺激增强了消退记忆的回忆。这项研究的结果将为理解灭绝记忆是如何在单个神经元的水平上编码提供重要的基础。该项目为波多黎各的研究生和本科生创造了一个独特的机会，学习多学科和协作的科学方法。两个实验室的学生都将参与该项目，并将在神经科学学会年会上展示他们的成果。