Role of the prefrontal cortex in behavioral modulation of basal forebrain activit

描述（由申请人提供）：前额叶皮层（PFC）是参与目标导向行为和自上而下调节感觉处理的关键区域。虽然已经做了大量工作来研究PFC中与任务相关的活动，但其职能组织的基本原则仍然不清楚。在这里，我建议调查的有趣的可能性，PFC神经元之间的功能相似性是密切相关的共享的投射目标，使用PFC投射到基底前脑（BF）作为一个例子。这条通路被认为部分介导了PFC对感觉加工的自上而下的调节，但这一想法仍然缺乏实验支持。使用最先进的逆行病毒追踪技术，我将首先对PFC-BF通路进行详细的解剖学表征。下一步将是将联合收割机与清醒的行为小鼠的双光子钙成像相结合，以识别PFC中的BF投射细胞，并测量它们与任务相关的活动，将其与该区域内的其他细胞群进行对比。这些结果将有助于了解前额叶皮层的功能组织，以及感觉加工自上而下调制的电路基础。这些知识具有很大的潜在临床意义，因为PFC和BF参与了几种神经系统疾病，如阿尔茨海默病，精神分裂症和帕金森病相关的痴呆症。

DESCRIPTION (provided by applicant): The prefrontal cortex (PFC) is a crucial region involved in goal-directed behavior and top-down modulation of sensory processing. Although much work has been done to study task-related activity in the PFC, the principles underlying its functional organization remain unclear. Here I propose to investigate the intriguing possibility that the functional similarity between PFC neurons is closely related to their shared projection targets, using the PFC projection to the basal forebrain (BF) as a case in point. This pathway is thought to partly mediate PFC's top-down modulation of sensory processing, but this idea still lacks experimental support. Using state-of-the- art retrograde viral tracing techniques, I will firt perform a detailed anatomical characterization of the PFC-BF pathway. The next step will be to combine such techniques with two-photon calcium imaging in awake, behaving mice to identify BF- projecting cells in the PFC and measure their task-related activity, contrasting it with other cell populations within the region. The results will shed light on the functional organization of te PFC, as well as the circuit underpinnings of top-down modulation of sensory processing. Such knowledge is of great potential clinical relevance, given the involvement of PFC and BF in several neurological disorders, such as Alzheimer's disease, schizophrenia, and Parkinson's disease-related dementia.