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.
Working memory is greatly affected by aging. Understanding where in the brain and how working memory is maintained is a critical step in understanding the pathological basis of impaired working memory in advanced age. The proposed research will determine which cortical and subcortical areas are required for visual working memory and how their interaction enables the maintenance of the memory trace.
