Abstract

Monitoring spiking activity across large neuronal populations at behaviorally relevant timescales is critical for understanding neural circuit function. Voltage imaging requires kilohertz sampling rates which reduce fluorescence detection to near shot noise levels. High-photon flux excitation can overcome photon-limited shot noise but photo-bleaching and photo-damage restrict the number and duration of simultaneously imaged neurons. We investigated an alternative approach aimed at low two-photon flux, voltage imaging below the shot noise limit with the goal of achieving simultaneous high-speed, deep-tissue imaging of more than one hundred densely labeled neurons over one hour in awake behaving mice.

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