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

描述（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的感觉加工调节的关键区域。尽管已经做了很多工作来研究PFC中与任务相关的活动，但其功能组织的基本原理仍不清楚。在这里，我建议研究一个有趣的可能性，即PFC神经元之间的功能相似性与它们共同的投射目标密切相关，以PFC投射到基底前脑（BF）为例。这条通路被认为部分地介导了PFC自上而下的感觉处理调节，但这一观点仍缺乏实验支持。使用最先进的逆行病毒追踪技术，我将首先对PFC-BF途径进行详细的解剖表征。下一步将是将这种技术与双光子钙成像结合起来，在清醒的行为小鼠中识别PFC中的BF-突起细胞，测量它们的任务相关活动，并将其与该区域内的其他细胞群进行对比。这些结果将揭示PFC的功能组织，以及自上而下的感觉处理调制的电路基础。鉴于PFC和BF与多种神经系统疾病（如阿尔茨海默病、精神分裂症和帕金森病相关痴呆）有关，这些知识具有巨大的潜在临床意义。

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.