Cortical dynamics underlying visual working memory

下一盘棋，开车，甚至读这句话，都需要大脑在短时间内保持和整合信息。这种信息的保留和整合是通过工作记忆完成的。同样的潜在机制也可能允许我们持有和比较我们的想法，并使我们能够对自己和世界产生一致的认识。此外，了解信息是如何在工作记忆中保留的，是了解老年工作记忆受损的病理基础的关键一步。在人类和非人类灵长类动物中进行的开创性研究导致了一种假设，即工作记忆是由相互关联的大脑皮层区域组成的层次结构维持的。几个大脑皮层区域显示出与工作记忆相关的活动，这一事实支持了这一点。然而，每个区域对工作记忆的因果贡献仍不清楚。在该奖项的指导阶段，拟议的研究将为小鼠开发一项视觉工作记忆任务。这将打开一扇机会之窗，利用老鼠可用的复杂实验工具，在系统和细胞水平上使用新的方法来研究视觉工作记忆。此外，在指导阶段，我将开发一种方法来选择性地沉默小鼠不同的视觉皮质区域，使用本征成像来识别不同的视觉皮质区域，并使用激光扫描电流系统来定位光的光遗传扰动。这一方法将使我能够在奖项的独立阶段评估工作记忆中视觉或非视觉皮质区域的因果参与。在该奖项的独立阶段，我希望带领一个研究团队来确定视觉工作记忆需要哪些皮质和皮质下区域，以及它们之间的相互作用如何使记忆痕迹得以维持。此外，这项拟议的研究将开发一个受我的实验观察约束的工作记忆的计算模型。该奖项的指导阶段的拟议环境是加州大学旧金山分校，由Massimo Scanziani博士指导。斯坎齐亚尼博士是世界著名的视觉皮层环路专家，也是著名的森林和支持年轻科学家的导师。加州大学旧金山分校在视觉研究和系统神经科学方面非常强大，将为我提供大量的资源、技术支持和协作环境，以确保我成功地过渡到一名独立的研究人员。

Playing a game of chess, driving a car, or even reading this sentence all require that the brain retain and integrate information over short periods of time. This retaining and integration of information is accomplished by working memory. The same underlying mechanisms may also allow us to hold and compare our thoughts and enable us to create a coherent awareness about our self and the world. Further, understanding how information is retained during working memory is a critical step in understanding the pathological basis of impaired working memory in advanced age. Pioneering studies in humans and non-human primates have led to the hypothesis that working memory is maintained by a hierarchy of interconnected cortical areas. This is supported by the fact that several cortical areas show working memory related activity. Yet, the causal contribution of each area to working memory remains unknown. In the mentored phase of the award, the proposed study will develop a visual working memory task for mice. This will open a window of opportunity for using novel approaches to study visual working memory at both the systems and cellular level using the sophisticated experimental tools available in the mouse. In addition, during the mentored phase I will develop an approach to selectively silence distinct visual cortical areas in the mouse, using intrinsic imaging for identification of the distinct visual cortical areas and a laser scanning galvo system for localizing the light for optogenetic perturbations. This approach will allow me, during the independent phase of the award, to assess the causal involvement of visual or non-visual cortical areas in working memory. In the independent phase of the award, I hope to lead a research team to determine which cortical and subcortical areas are required for visual working memory and how their interaction enables the maintenance of the memory trace. Further, the proposed study will develop a computational model of working memory constrained by my experimental observations. The proposed environment for the mentored phase of the award is UCSF under the mentorship of Dr. Massimo Scanziani. Dr. Scanziani is a world-renowned expert in visual cortical circuits and a reputed mentor for foresting and supporting young scientists. UCSF is very strong in vision research and systems neuroscience, and will provide me with substantial resources, technical support, and a collaborative environment to ensure my successful transition into an independent investigator.