Label-free Optical Recording of Neuroelectric Activities

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Project Summary Understanding how a network of interconnected neurons receives, stores and processes information requires parallel and high quality recording of neuroelectric signals. Intracellular recording techniques such as patch clamp are invasive and limited to recording 1-2 cells. While extracellular multielectrode arrays can record multiple cells, they are pre-fabricated and thus can only probe fixed locations. Optical detection of electric activities provides the needed spatial flexibility. Calcium sensors such as GcaMP have a slow time response and not suitable to record fast-spiking pacemaker neurons such as dopaminergic neurons. Voltage-sensitive fluorescence proteins and dyes have much faster time response, but their recording time is usually limited by photobleaching. In this project, we will demonstrate an orthogonal approach of optical recording. This method, Electrochromic Optical Recording of Electric potentials (ECORE) makes use of a unique material property – optical absorption of an electrochromic film depends on applied voltages. We detect the optical reflection of an electrochromic film to read out cellular electrical activities. The method is truly label-free, i.e. free of any molecular probes that need to be incorporated into cells and perturb cellular physiology, and not limited by photobleaching or photo-toxicity. In preliminary work, we have built a sensitive optical setup that is able to detect the reflectivity change of the electrochromic film in response to electrical potentials as small as 10 microvolts. Indeed, we have used ECORE to successfully record single-cell action potentials in neurons, cardiomyocytes, and brain tissues. With this project, we plan to dramatically expand ECORE capabilities by developing a scanning ECORE platform for parallel detection and an ECORE microscope for subcellular measurement of neuroelectric activities. We will use ECORE to probe the functional connectivity of dopaminergic neurons in midbrain area. Accomplishment of this work will result in a new class of electrophysiological tools that can be used by other research groups.