This project aims to develop the 2P-ActivityScope, a revolutionary new microscope based on a technological breakthrough called second-generation Scanned Line Angular Projection (SLAP2) two photon laser scanning microscopy that was recently developed by Dr. Kaspar Podgorski (Janelia Research Campus, Howard Hughes Medical Institute, Ashburn, VA). The game-changing innovation in the 2P-ActivityScope is the ability to perform unparalleled (i) optical imaging of neuronal activity in populations of neurons at subcellular spatial resolution and temporal resolution in the millisecond range both in vivo and in vitro using a variety of fluorescent indicators (e.g. voltage, [neurotransmitter]) as well as (ii) high-resolution volumetric calcium imaging of columns of cortical neurons at 40 Hz in vivo. These capabilities are crucial for ultimately decoding how information is represented and processed by the billions of densely interconnected neurons comprising the mammalian central nervous system. Neither contemporary 2-photon microscopes, functional magnetic resonance imaging, inserting electrodes into the brain, or fiber photometry can serve this need. This project will disseminate and improve upon the original, lab-built SLAP2 invention to create a commercial product for this important new technology. Based on pilot work performed at Janelia, it is clear that the 2P-ActivityScope will make a significant impact on the field of neuroscience research, including advancing studies focused on alterations in CNS circuitry associated with neurodevelopmental, neuropsychiatric and neurodegenerative disorders. Ultimately, this will result in an improved basis for developing novel treatment strategies for a wide spectrum of complex brain diseases. In Phase I we will demonstrate feasibility of this novel technology by developing prototype hardware and software; work in Phase II will focus on creating the full functionality of the 2P-ActivityScope for commercial release. We will perform extensive feasibility studies, product validation and usability studies of the 2P-ActivityScope in close collaboration with Dr. Podgorski and our academic collaboration partners. A competing technology is not commercially available. Public Health Relevance Statement Narrative This project develops a revolutionary new microscope based on a technological breakthrough called Scanned Line Angular Projection two photon laser scanning microscopy. This microscope will enable optical imaging of neuronal activity at subcellular spatial resolution with a temporal resolution in the millisecond range both in vivo and in vitro using a variety of fluorescent indicators (e.g. voltage and neurotransmitter). As a result, new avenues of neuroscience research will become possible providing promise for the elucidation of novel biological mechanisms associated with human brain disease, and ultimately the basis for developing novel therapies to prevent and treat complex brain diseases.
Project Terms: Biotechnology ; Biotech ; Brain ; Brain Nervous System ; Encephalon ; Brain Diseases ; Brain Disorders ; Encephalon Diseases ; Intracranial CNS Disorders ; Intracranial Central Nervous System Disorders ; Calcium ; Cells ; Cell Body ; Central Nervous System Diseases ; CNS Diseases ; CNS disorder ; Central Nervous System Disorders ; Cerebral cortex ; Communities ; Electrodes ; Feasibility Studies ; Human ; Modern Man ; In Vitro ; Institutes ; Interest Group ; Laser Electromagnetic ; Laser Radiation ; Lasers ; Photoradiation ; Light ; Motion ; Mice ; Mice Mammals ; Murine ; Mus ; Nerve Cells ; Nerve Unit ; Neural Cell ; Neurocyte ; neuronal ; Neurons ; Nerve Transmitter Substances ; Neurotransmitters ; optical ; Optics ; Photometry ; Production ; Research ; Development and Research ; R & D ; R&D ; research and development ; Cell Communication and Signaling ; Cell Signaling ; Intracellular Communication and Signaling ; Signal Transduction Systems ; Signaling ; biological signal transduction ; Signal Transduction ; Societies ; Software ; Computer software ; Technology ; Testing ; Time ; tomography ; Wisconsin ; Work ; Generations ; Artifacts ; Morphologic artifacts ; base ; Microscope ; improved ; Surface ; Phase ; Biological ; Medical ; Fiber ; Stimulus ; Individual ; Collaborations ; Letters ; Research Specimen ; Specimen ; Functional MRI ; fMRI ; Functional Magnetic Resonance Imaging ; Knowledge ; Msec ; millisecond ; Complex ; Scanning ; Pattern ; System ; Degenerative Neurologic Diseases ; Degenerative Neurologic Disorders ; Nervous System Degenerative Diseases ; Neural Degenerative Diseases ; Neural degenerative Disorders ; Neurodegenerative Diseases ; Neurologic Degenerative Conditions ; degenerative diseases of motor and sensory neurons ; degenerative neurological diseases ; neurodegenerative illness ; Neurodegenerative Disorders ; interest ; voltage ; biological sensor ; Biosensor ; Laser Scanning Microscopy ; novel ; novel technologies ; new technology ; Devices ; Column of Bertini ; Renal Column of Bertini ; Cortical Column ; CNS Nervous System ; Central Nervous System ; Neuraxis ; Neuromodulator ; preventing ; prevent ; Address ; Resolution ; in vivo ; Neurosciences Research ; Slice ; Validation ; Process ; developmental ; Development ; Neurological Development Disorder ; Neurodevelopmental Disorder ; Behavioral ; imaging ; Image ; optic imaging ; optical imaging ; 2-photon ; two-photon ; digital ; design ; designing ; next generation ; Population ; innovation ; innovate ; innovative ; usability ; novel therapeutics ; new drug treatments ; new drugs ; new therapeutics ; new therapy ; next generation therapeutics ; novel drug treatments ; novel drugs ; novel therapy ; prototype ; treatment strategy ; temporal measurement ; temporal resolution ; time measurement ; invention ; neuropsychiatric disorder ; neuropsychiatric disease ;
