Single Photon Kilohertz Frame Rate Imaging of Neural Activity

Establishing the biological basis of cognition and its disorders will require high precision spatiotemporal measurements of neural activity. Recently developed genetically encoded voltage indicators (GEVIs) report both spiking and subthreshold activity of identified neurons. However, maximally capitalizing on the potential of GEVIs will require imaging at millisecond time scales, which remains challenging with standard camera systems. Here, application of single photon avalanche diode (SPAD) sensors is reported to image neural activity at kilohertz frame rates. SPADs are electronic devices that when activated by a single photon cause an avalanche of electrons and a large electric current. An array of SPAD sensors is used to image individual neurons expressing the GEVI Voltron-JF525-HTL. It is shown that subthreshold and spiking activity can be resolved with shot noise limited signals at frame rates of up to 10 kHz. SPAD imaging is able to reveal millisecond scale synchronization of neural activity in an ex vivo seizure model. SPAD sensors may have widespread applications for investigation of millisecond timescale neural dynamics.