Prefrontal and amygdalar pathways to memory-related medial temporal cortex

描述(申请人提供)：拟议研究的目标是调查前额叶和杏仁核通路对内侧颞叶(MTL)记忆相关皮质的贡献。最重要的假设是，这些通路与MTL鼻皮质的相互作用构成了一个整合了注意背景与情绪和助记信息的电路。前扣带回(ACC)内侧前额叶皮质的尾侧部分被认为参与监测与先前学习结果的记忆有关的正在进行的行为，但该皮质如何影响MTL的通路尚不清楚。最近的证据表明，内侧前额叶皮质促进了MTL鼻侧皮质之间的交流。这些发现表明，ACC在皮质-海马体的处理中起着重要的作用，这一问题因以下事实而变得更加复杂：进出海马体的信息传递是通过鼻皮质中的局部抑制来实现的。这项拟议的研究将探讨Acc和杏仁核与恒河猴MTL内兴奋和抑制系统的突触相互作用，以研究：1)从内侧前额叶皮质到鼻皮质的投射；2)ACC轴突是否与鼻皮质中不同类别的抑制和兴奋回路突触；3)ACC和杏仁核的投射是否在鼻皮质协同作用。前额叶通路将被多个不同的神经示踪剂结合双重或三重标记的免疫组织化学标记，以定位MTL内的轴突终末以及兴奋性和抑制性神经元。将在光、共焦和电子显微镜水平收集数据以进行定量分析。了解ACC和杏仁核如何冲击鼻皮质助记回路，进而了解注意环境如何与助记和情绪信息整合，对于理解名义记忆功能和深入了解焦虑症的病理机制至关重要。

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.