Development of a miniature implantable device to allow transfer of neural information from one brain area to another will have a major impact on the understanding of brain function and will be applicable to treatment of brain disease. The proposed research spans neuroscience, materials science, physics and engineering, and will provide excellent interdisciplinary research opportunities for students. Dissemination of the work will occur through teaching, additional educational outreach, opportunities for undergraduates, and journals and conference publications. The capability of this research to develop an optical feedback control to repair brain function will captivate these future scientists.
Non-invasive feedback control to repair brain function is one of the ultimate goals in neuroscience. The recent and evolving development of genetically encoded fluorescent indicators and optogenetics makes optical readout and control a real possibility. However, there is still a critical need to understand how an optical feedback system can fully recover function in an awake behaving animal. This proposal seeks to demonstrate for the first time the actual recovery of function in an awake-behaving animal using an engineered optical feedback system. The project will be performed by a highly interdisciplinary team with extensive expertise in neuroscience, optogenetics, and cognitive research in awake behaving animals along with experts in optical and MEMS devices. The proposal combines the technology development side with behavioral research with the potential for major discoveries. Unprecedented progress in the study of brain function will be enabled with the proposed device. The PIs have recently developed technology for a lightweight head-mounted miniature multiphoton microscope that can image over hundreds of neurons in three dimensions in brain tissue. The technology is the first to use electrowetting optics for non-mechanical steering of the excitation laser and enables single cell resolution imaging. We propose to combine a spatially shaped second laser at a different wavelength from our excitation laser to allow both imaging and directed optogenetic stimulation of neurons. Importantly, modulation of neural activity on the level of individual neurons is essential for controlling function in the brain. Therefore readout and control by optics has a real potential to restore function as opposed other methods such as ultrasound, EEG, and fMRI that are theoretically limited in spatial resolution. We propose to readout and control firing of individual neurons in the piriform cortex using a real-time feedback control system. We will use behavior studies in mice to determine if association of olfactory identity with reward can be recovered as we selectively turn on and off the input nerve connections to the piriform cortex where odor identity is thought to be represented. The study will allow us to identify which neurons contain information essential for decision making. The oscillatory basis for information transfer can be tested using certain frequency ranges or phases of neural activity. These studies will be useful for testing models of neural circuit function and applicable for neuroengineering devices for therapeutic use.
