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

Brown University, Providence RI

Investigators

Abstract

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.