Abstract: The invention generally relates to optical methods for characterizing the effects of compounds on pain and other sensory phenomena. The effect of compounds on pain and other sensory phenomena may be characterized using dorsal root ganglion (DRG) neurons or sensory neurons expressing optogenetic proteins that allow neural activity to be stimulated and detected optically. The invention provides cell-based optical assays for studying the molecular and cellular bases of pain and sensory phenomena and as platforms to screen and validate drugs, e.g., for pre-clinical trials.

Abstract: The invention provides methods, cells and constructs for optical measurement of membrane potential. These methods can be used in cells that are not accessible to presently available methods using electrodes. The methods can be directed to, for example, high-throughput drug screening assays to determine agents that can affect membrane potential of a target cell.

Abstract: Various aspects of the present invention are generally directed to systems and methods for imaging at high spatial and/or temporal resolutions. In one aspect, the present invention is generally directed to an optical microscopy system and related methods adapted for high spatial and temporal resolution of dynamic processes. The system may be used in conjunction with fluorescence imaging wherein the fluorescence may be mediated by voltage-indicating proteins. In some cases, time resolutions may be enhanced by fitting predefined temporal waveforms to signal values received from an image. The system may also contain a high numerical aperture objective lens and a zoom lens located in an imaging optical path to an object region. Other aspects of the present invention are generally directed to techniques of making or using such systems, kits involving such systems, manufactured storage devices able to implement such systems or methods, and the like.

Abstract: The invention provides methods for characterizing cellular physiology by incorporating into an electrically excitable cell an optical reporter of, and an optical actuator of, electrical activity. A signal is obtained from the optical reporter in response to a stimulation of the cell. Either or both of the optical reporter and actuator may be based on genetically-encoded rhodopsins incorporated into the cell. The invention provides all optical methods that may be used instead of, or as a complement to, traditional patch clamp technologies and that can provide rapid, accurate, and flexible assays of cellular physiology.