Prefrontal and amygdalar pathways to memory-related medial temporal cortex

描述（由申请人提供）：拟议研究的目的是研究前额叶和杏仁核通路对内侧颞叶（MTL）记忆相关皮层的贡献。最重要的假设是，这些通路与MTL鼻皮层的相互作用构成了一个将注意力背景与情感和记忆信息整合在一起的回路。前扣带（ACC）内侧前额叶皮层的尾侧部分被认为参与监控与先前学习结果的记忆有关的持续行为，但该皮层的通路如何影响MTL尚不清楚。最近的证据表明，内侧前额叶皮层促进了MTL的鼻皮质之间的交流。这些发现表明，ACC在皮质海马处理中起着重要作用，这一问题由于信息传递到海马和从海马的信息传递是通过鼻皮质内的局部抑制来控制的这一事实而复杂化。拟进行的研究将探讨猕猴MTL中ACC和杏仁核与兴奋和抑制系统之间的突触相互作用，以研究：1)内侧前额叶皮层向鼻皮质的投射；2) ACC轴突在鼻皮层是否具有不同类型的抑制性和兴奋性回路；3) ACC和杏仁核的投射是否在鼻皮质中协同作用。前额叶通路将使用多种不同的神经示踪剂结合双或三重标记免疫组织化学来标记轴突末端以及MTL内的兴奋性和抑制性神经元。数据将收集在光，共聚焦和电子显微镜水平进行定量分析。了解前扣带皮层和杏仁核如何影响鼻皮层记忆回路，进而了解注意背景如何与记忆和情绪信息相结合，对于理解名义记忆功能和深入了解焦虑障碍中观察到的病理至关重要。

DESCRIPTION (provided by applicant): The goal of the proposed studies is to investigate the contribution of prefrontal and amygdalar pathways to memory-related cortices in the medial temporal lobe (MTL). The overarching hypothesis is that the interaction of these pathways with MTL rhinal cortices constitutes a circuit that integrates attentional context with emotional and mnemonic information. The caudal portion of the medial prefrontal cortex in the anterior cingulate (ACC) is thought to be involved in monitoring on-going behavior pertaining to memory of previously learned outcomes, but how pathways from this cortex impinge on the MTL is not well understood. Recent evidence has shown that the medial prefrontal cortex facilitates communication between the rhinal cortices of the MTL. These findings suggest that ACC plays an important role in corticohippocampal processing, an issue compounded by the fact that information transfer, both to, and from the hippocampus is gated via local inhibition within the rhinal cortices. The proposed studies will address the largely unexplored synaptic interactions of the ACC and amygdala with excitatory and inhibitory systems within the rhesus monkey MTL to investigate: 1) projections from the medial prefrontal cortex to rhinal cortices; 2) whether ACC axons synapse with distinct classes of inhibitory and excitatory circuits in rhinal cortices; 3) whether projections from the ACC and amygdala are positioned to act synergistically in rhinal cortices. Prefrontal pathways will be labeled with multiple distinct neural tracers combined with double or triple labeling immunohistochemistry to map axonal terminations as well as excitatory and inhibitory neurons within MTL. Data will be collected at the light, confocal and electron microscope level for quantitative analyses. Understanding how the ACC and the amygdala impinge upon the rhinal cortical mnemonic circuit, and by extension how attentional context is integrated with mnemonic and emotional information, is critical for understanding nominal memory function and for gaining insight into the pathologies observed in anxiety disorders. PUBLIC HEALTH RELEVANCE: Clinical findings and imaging studies in patients suffering from anxiety disorders, including post traumatic stress disorder, indicate that symptoms may manifest due to disruptions in the ACC- amygdala-rhinal cortical circuit affecting the integration of context with emotionally salient memories. The proposed studies address the synaptic interactions underlying the synthesis of contextual (ACC) and emotional (amygdala) information with memory related circuits (rhinal cortices), which is prerequisite to the development of therapies for these psychiatric disorders.