Cortico-limbic circuits for learning and memory

这项研究的主要目的是在新的方向上推广一种非常成功的策略，以识别涉及记忆特定方面(物体识别、时间顺序和空间记忆)的神经通路和相关的神经递质。我们的主要“工作假说”认为，记忆功能的不同方面依赖于独立和不同的神经回路，在计划未来行动时，前额叶皮质在使用记忆方面发挥着关键作用。作为行为神经科学领域的一个项目，人们认真注意使用复杂可靠的行为测试来评估学习和记忆的具体方面。关键的神经通路是通过将可逆脑损伤应用于大脑相对大脑半球中选定通路的起点或末端区域来识别的。一旦给定的神经通路与记忆功能的某一方面联系起来，就有可能发现哪些神经递质和受体参与其中。利用大脑微透析和适当的化学分析，我们可以在额叶和相关的大脑区域扩展对工作和时间顺序记忆功能的神经化学分析。我们还建议研究额叶在记忆中对先前学习到的联想和行为反应的“消亡”的作用，以提高对消亡的神经生物学基础的认识。总而言之，这一研究计划的结果将带来对涉及记忆功能关键方面的神经系统的新见解。此外，它们还将为开发新化合物提供临床前平台，这些化合物可能会增强与年龄相关的记忆缺陷相关的弱记忆功能，或者阻止导致焦虑和相关心理障碍的侵入性记忆。

The main objective of this research is to extend, in new directions, a highly successful strategy for identifying neural pathways and related neurotransmitters involved in specific aspects of memory (object recognition, temporal order and spatial memory). Our main 'working hypothesis' holds that different aspects of memory function depend on separate and distinct neural circuits, with a critical role for the prefrontal cortex in the use of memory in planning future action. As a project in the field of behavioural neuroscience, careful attention is paid to the use of sophisticated and reliable behavioural tests to assess specific aspects of learning and memory. Critical neural pathways are identified using reversible brain lesions applied to either the origin or terminal region of selected pathways in opposite brain hemispheres of the brain. Once a given neural pathway has been linked to an aspect of memory function, it is then possible to discover which neurotransmitters and receptors are involved. Using brain microdialysis and appropriate chemical assays, we can extend the neurochemical analyses of working and temporal order memory function, in the frontal lobes and related brain regions.   We also propose to study the role of the frontal lobes in memory for 'extinction' of previously learned associations and behavioural responses to improve knowledge of neurobiological bases of extinction. Collectively, results of this program of research will lead to novel insights into the neural systems involved in key aspects of memory function.  They will also provide a preclinical platform for the development of novel compounds that may enhance 'weak' memory function associated with age-related memory deficits or block intrusive memories that underlie anxiety and related psychological disorders.