Dual-channel Sub-millisecond Resolution Neural Imaging System

Project Summary Abstract The investigation of the complex neural dynamics and the cognitive functions of the brain requires noninvasive recording tools with high spatio temporal resolutionSub cellular resolution fluorescence imaging microscopybased on either voltage indicators or calcium sensitive fluorescent proteinsenables parallel recording of the activity of spatially distributed neuron populationsHoweverthe speed of current fluorescence imaging techniques is largely limited to a few hundred frames per secondexcluding the use of some extremely sophisticated scientific cameras of substantially high noise and prohibitively high costThis speed limit originates from not only instrumentation technology constrainssuch as the slow scan in scanning microscopes or the low frame rate of the cameras used in wide field microscopesbut also the fundamental photon stochastic noise of the low level fluorescent signalsThe milliseconds or slower temporal resolution substantially precludes measuring the precise timing of the generation and propagation of neuron spikes or spike trainswhich is the key component of neural signalingPhysical Sciences IncPSIand Massachusetts Institute of TechnologyMITpropose to develop and demonstrate a unique fluorescence imaging system that will enable parallel recording of multiple neuron populations with sub cellular spatial resolution and sub millisecond temporal resolutionThis novel neural recording system will have two fluorescence detection channelsone to record the slow dynamics of all the neurons in a given field of view with a sub cellular spatial resolutionand a second one with submillisecond temporal resolution to study fast spiking dynamics of neuronswhich can be arbitrarily selected under the guidance of the first channelThis high speed parallel neural recording function is enabled by an innovative imaging concept that uses a high sensitivity single point detector to collect fluorescence signals generated at multiple locationsor neuron populationswhile the spatial information is encoded by modulating the excitation light at each location at a unique temporal frequencyIn Phase Iwe will develop and optimize a bench top microscope at PSI facilityand then move it to MIT for testing using cultured neuronsThe small form factors of all the components will make it possible to develop a device that is compact enough to be head mounted on small animalssuch as rats or miceDevelopment and evaluation of head mounted devices will occur during a subsequent Phase II programThis Randamp D project will lead to a low costs solution for non invasive recording of large neuron populations with high spatiotemporal resolutionproviding an important enabling tool for cutting edge brain studies and research Project Narrative This Randamp D program will demonstrate a highly innovative and low cost imaging tool that addresses a technology gap in neuroscience research for non invasively recording of large neuron populations with high spatial and temporal resolutionSuccessful development and commercialization of this technology will significantly advance neuroscience research and clinical practiceand thus improve the treatment of various mental health problems and neurology diseases