Cortico-limbic circuits for learning and memory

用于学习和记忆的皮质边缘回路

• 批准号: 7808-2011
• 负责人: Phillips, Anthony
• 金额: $ 3.42万
• 依托单位: University of British Columbia
• 依托单位国家: 加拿大
• 项目类别: Discovery Grants Program - Individual
• 财政年份: 2014
• 资助国家: 加拿大
• 起止时间: 2014-01-01 至 2015-12-31
• 项目状态: 已结题
• 来源: https://www.nserc-crsng.gc.ca/ase-oro/Details-Detailles_eng.asp?id=544450
• 关键词: Cortico; limbic; circuits; learning; memory

The main objective of this NSERC-funded research project is to extend our understanding of the neural mechanisms by which newly learned behaviours are instantiated into long-term memories. Using a small 'interference peptide' (patent-pending), we are able to block the internalization of the AMPA class of ionotropic glutamate receptors and thereby block the final step required for a form of synaptic plasticity called Long-term Potentation (LTD.) We use this molecular tool in conjunction with sophisticated and behavioural tests to assess the role of synaptic plasticity in specific aspects of learning and memory, several of which we have refined in our recent studies. This research program will build on recent success in linking LTD to processes responsible for response flexibility and extinction of previously acquired memory. Following initial experiments in which the drugs are injected via the intravenous route, and selective memory disruption achieved in a specific behavioural test, subsequent experiments will attempt to localize the neural structure(s) in which a disruption of LTD reproduces the effects observed with systemic drug administration. With the advent of these new tools for manipulating LTD in the brain, we can now examine directly the functional effects of 'depotentiation" of LTP, by induction of LTD, on our brain-stimulation signal detection procedure. Our working hypothesis maintains that enhanced signal detection following LTP will be reversed by an 'LTD' stimulation protocol and that this effect can be blocked by administration of our 'interference peptide'. This project has important theoretical implication and should provide new insights into synaptic plasticity and information processing in brain.

这个NSERC资助的研究项目的主要目标是扩展我们对神经机制的理解，通过这些机制，新学习的行为被实例化为长期记忆。使用一种小的“干扰肽”（正在申请专利），我们能够阻断AMPA类离子型谷氨酸受体的内化，从而阻断一种称为长时程增强（LTD）的突触可塑性形式所需的最后一步。我们使用这种分子工具结合复杂的行为测试来评估突触可塑性在学习和记忆的特定方面的作用，其中一些我们已经在最近的研究中进行了改进。这项研究计划将建立在最近成功地将LTD与负责反应灵活性和先前获得的记忆消退的过程联系起来的基础上。 在最初的实验中，药物通过静脉途径注射，并在特定的行为测试中实现选择性记忆破坏，随后的实验将试图定位神经结构，其中LTD的破坏再现了全身给药时观察到的效果。随着这些在大脑中操纵LTD的新工具的出现，我们现在可以直接检查LTP的“去增强”的功能效应，通过LTD的诱导，对我们的脑刺激信号检测程序。 我们的工作假设认为，增强信号检测LTP后将被逆转的“LTD”刺激协议，这种效果可以通过管理我们的“干扰肽”。 本研究具有重要的理论意义，为研究突触可塑性和脑内信息加工提供了新的视角。