Cortical dynamics underlying visual working memory

视觉工作记忆的皮层动力学

• 批准号: 9754448
• 负责人: Arbora Resulaj
• 金额: $ 4.16万
• 依托单位: UNIVERSITY OF CALIFORNIA, SAN FRANCISCO
• 依托单位国家: 美国
• 财政年份: 2019
• 资助国家: 美国
• 起止时间: 2019-05-01 至 2019-08-31
• 项目状态: 已结题
• 来源: https://reporter.nih.gov/project-details/9754448
• 关键词: Affect; Aging; Area; Attention; Automobile Driving; Award; Awareness; Behavior; Behavioral; Behavioral Paradigm; Biological Models; Brain; Computer Simulation; Data; Discrimination; Elderly; Electrophysiology (science); Ensure; Environment; Goals; Human; Image; Impairment; Lasers; Lead; Learning; Lesion; Light; Maintenance; Memory; Mentors; Mentorship; Modeling; Mus; Neurons; Neurosciences; Odors; Pathologic; Phase; Play; Population; Publishing; Reading; Recurrence; Research; Research Personnel; Resources; Role; Scanning; Scientist; Sensory; Short-Term Memory; Signal Transduction; Stimulus; Synapses; Synaptic plasticity; System; Technical Expertise; Techniques; Testing; Thalamic structure; Theoretical model; Thinking; Time; Vision research; Visual; Visual Cortex; Visual attention; Work; collaborative environment; experimental study; extrastriate visual cortex; forest; neural circuit; nonhuman primate; novel strategies; optogenetics; predictive modeling; relating to nervous system; therapy development; tool

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.

下棋、开车，甚至阅读这句话，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来完成的。相同的潜在机制也可能使我们能够保持和比较我们的想法，并使我们能够对自我和世界形成连贯的认识。此外，了解工作记忆中信息如何保留是了解高龄工作记忆受损的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得出了这样的假设：工作记忆是由相互关联的皮质区域的层次结构维持的。几个皮质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。这将为利用小鼠中可用的复杂实验工具在系统和细胞水平上使用新方法研究视觉工作记忆打开一扇机会之窗。此外，在指导阶段，我将开发一种选择性沉默小鼠不同视觉皮层区域的方法，使用固有成像来识别不同的视觉皮层区域，并使用激光扫描振镜系统来定位光遗传学扰动的光。这种方法将使我能够在奖励的独立阶段评估工作记忆中视觉或非视觉皮层区域的因果关系。在该奖项的独立阶段，我希望带领一个研究团队确定视觉工作记忆需要哪些皮层和皮层下区域，以及它们的相互作用如何实现记忆痕迹的维持。此外，拟议的研究将开发一个受我的实验观察限制的工作记忆计算模型。 该奖项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。 Scanziani 博士是视觉皮层回路领域的世界知名专家，也是造林和支持年轻科学家的著名导师。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，将为我提供大量资源、技术支持和协作环境，以确保我成功过渡为独立研究者。