RII Track-4:Acquiring and propagating expertise in closed-loop precision optical control of neuronal activity using spatial light modulation (SLM) combined with multiphoton imaging

非技术描述：脑功能在很大程度上是由相互作用的神经细胞的复杂回路决定的。这些电路的排列和神经细胞相互作用的方式是复杂的，目前还不太清楚。该项目将利用密歇根大学的专业知识和设施来开发利用关键新技术的技能，该技术将深入了解这些神经回路的工作原理。这项技术允许使用光精确控制大脑中的神经细胞，使科学家能够确定神经元如何在电路中协同工作。这将有助于科学家了解我们如何感知、感知、移动和思考的机制。同样，它将为神经和精神疾病中出现的问题以及治疗这些问题的策略提供见解。获得这些关键的新技术将对PI产生广泛而持久的影响。年代的事业。这个项目将使PI能够发展和改进他的工作，从而在理解大脑运作方面取得根本性的进步。最后，将这项技术转让给布朗大学的其他科学家和学生，并将提高罗德岛州的研究能力。技术描述：神经科学的一个重要目标是了解神经元在电路行为中的因果作用。光遗传学在不同程度上解决了这个问题。视蛋白可以在基因靶向的神经元类型中表达，这样这些细胞就可以被光刺激。空间光调制（SLM）的最新创新使得精确控制光选择神经元成为可能。利用这种技术，PI将在体感皮质丘脑（CT）系统中进行实验。使用SLM光遗传学，将确定有效丘脑调节必须激活的CT细胞的数量，以及CT细胞非同步激活改变结果的程度。作为该项目的一部分，PI将接受使用全光闭环SLM系统的培训，该系统目前正在密歇根大学开发。在这个系统中，神经活动将使用指示器GCaMP6进行分析，GCaMP6在Ca存在时发出光信号。这些信号将被反馈到激光控制器，以保持理想的刺激水平。改进后的功能将为神经功能的行为研究提供关键的机会，闭环SLM在这项工作中具有潜在的变革潜力。更普遍的是，多光子显微镜正变得越来越便宜，并且可能在几年内被许多有合理资金支持的神经生理学实验室所使用。随着这些显微镜在当地实验室的普及，PI所获得的知识将变得越来越有价值。

Non-technical Description:Brain function is largely determined by complex circuits of interacting nerve cells. The arrangement of these circuits and the ways that the nerve cells interact with each other is complex and poorly understood at this time. This project will take advantage of the expertise and facilities at the University of Michigan to develop the skills to utilize a critical new technology that will yield insight into how these neural circuits work. This technology allows for precise control of nerve cells in the brain using light, allowing scientists to determine how neurons work together in circuits. This will help scientists to understand the mechanisms of how we sense, perceive, move, and think. Likewise, it will provide insight into problems that occur in neurological and psychiatric disease and strategies to treat those problems. Access to these critical new technologies will have broad and long lasting impacts on the PI?s career. This project will allow the PI to develop and improve his work in ways that would allow fundamental advances in understanding of brain operation. Finally, transfer of this technology to other scientists and students at Brown University, and will improve research capacity in Rhode Island.Technical Description: An important goal of neuroscience is to understand the causal role of neurons in circuit behavior. This is being addressed to varying degrees using optogenetics. Opsins can be expressed in genetically-targeted neuronal types, such that those cells can be stimulated with light. Recent innovations in spatial light modulation (SLM) have made it possible to precisely control optically selected neurons. Using this technology, the PI will conduct experiments in the somatosensory corticothalamic (CT) system. Using SLM optogenetics, the number of CT cells that must be active for effective thalamic modulation will be determined, and the degree to which non-synchronous activation of CT cells alters outcome. As part of this project, the PI will receive training in use of an all-optical closed-loop SLM system that is currently being developed at the University of Michigan. In this system, neural activity will be assayed using the indicator GCaMP6, which emits light signals in the presence of Ca. These signals will be fed back to laser controllers in order to maintain ideal stimulus levels. The improved capabilities will provide pivotal opportunities for behavioral studies of neural function, and closed-loop SLM has potentially transformative potential for this work. More generally, multiphoton microscopes are becoming progressively more affordable, and are likely to be within reach of many reasonably-funded neurophysiology labs within several years. The knowledge gained by the PI will become ever more valuable as these microscopes become available in local laboratories.