Optopatch: high-throughput all-optical electrophysiology for neural recording

DESCRIPTION provided by applicant Optopatch high throughput all optical electrophysiology for neural recording The convergence of stem cell genomic and advanced imaging technologies provides unprecedented ability to study human neural physiology in health and disease Traditionally intractable diseases schizophrenia autism Alzheimerandapos s ALS and Parkinsonandapos s are being modeled in vitro with stem cell derived cultures of human neurons Genome sequencing and more recently editing technologies are helping to disentangle the complex genetic interactions that contribute to the pathophysiology Yet a key challenge has been to probe neuronal function in stem cell derived disease models with single cell resolution adequate throughput and over repeated measurements Due to its low throughput manual electrophysiology is not compatible with drug screening Direct visualization of neural activity conversion of action potentials into flashes of light would revolutionize our study of neural circuits The Cohen Lab has developed a genetic construct that enables simultaneous optical stimulation and optical recording of electrical activity in neurons One protein converts blue ligh into electrical stimuli a second protein converts neuronal activity into flashes of near infrared fluorescence Q State Biosciences aims to develop the technology to take this tool from the lab to the marketplace The aim of this proposal is to develop a prototype instrument for simultaneous spatially resolved optical stimulation and imaging andquot Optopatchandquot in complex neuronal cultures This instrument will enable all optical electrophysiology in samples containing up to neurons with millisecond temporal resolution micron spatial resolution and independent stimulation and readout of each cell The Cohen Lab has a proof of principle machine with these capabilities Many neuroscience cardiology stem cell and pharmaceutical labs would like to use this tool However three further advances are needed for the technology to be widely adopted to create instrumentation which can perform robustly in daily use to write software to manage and analyze the torrents of high dimensional data that Optopatch generates and to develop stimulation analysis protocols that accentuate biologically meaningful features of the neural network e g excitability synaptic strength topology and plasticity PUBLIC HEALTH RELEVANCE Optopatch high throughput all optical electrophysiology for neural recording This proposal is to develop a machine that uses light to stimulate and record from thousands of neurons in parallel This technology will be useful in studying cell based models of neuropsychiatric and neurodegenerative diseases