Cortical dynamics underlying visual working memory

下棋、开车，甚至是读这句话，都需要大脑在短时间内保留和整合信息。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以让我们保持和比较我们的想法，使我们能够对自己和世界产生连贯的意识。此外，了解信息在工作记忆中的保留方式是理解老年工作记忆受损病理基础的关键一步。对人类和非人类灵长类动物的开创性研究提出了一种假设，即工作记忆是由相互连接的皮层区域的层次结构维持的。有几个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观点。然而，每个区域对工作记忆的因果贡献仍然未知。在该奖项的指导阶段，拟议的研究将为小鼠开发视觉工作记忆任务。这将为使用新的方法在系统和细胞水平上研究视觉工作记忆打开一扇机会之窗，使用小鼠中可用的复杂实验工具。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，使用固有成像来识别不同的视觉皮质区域，并使用激光扫描galvo系统来定位光遗传扰动的光。这种方法将允许我，在独立的奖项阶段，评估工作记忆中视觉或非视觉皮层区域的因果关系。在独立获奖阶段，我希望带领一个研究小组确定哪些皮层和皮层下区域是视觉工作记忆所必需的，以及它们之间的相互作用如何使记忆痕迹得以维持。此外，本研究将根据我的实验观察发展一个工作记忆的计算模型。该奖项的指导阶段的拟议环境是在Massimo Scanziani博士的指导下的UCSF。斯坎齐亚尼博士是世界知名的视觉皮层回路专家，也是著名的造林和支持年轻科学家的导师。UCSF在视觉研究和系统神经科学方面非常强大，并将为我提供大量的资源，技术支持和协作环境，以确保我成功过渡到独立研究者。

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.