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Updated: May 1, 2026

Photodiode-Based Optical Imaging for Recording Network Dynamics with Single-Neuron Resolution in Non-Transgenic Invertebrates
Published on: July 9, 2020
Imaging high-frequency voltage dynamics in multiple neuron classes of behaving mammals
Simon Haziza1, Radosław Chrapkiewicz1, Yanping Zhang2
1James H. Clark Center, Stanford University, Stanford, CA 94305, USA; CNC Program, Stanford University, Stanford, CA 94305, USA; Department of Biology, Stanford University, Stanford, CA 94305, USA.
Abstract:
Fluorescent genetically encoded voltage indicators report transmembrane potentials of targeted cell types. However, voltage-imaging instrumentation has lacked the sensitivity to track spontaneous or evoked high-frequency voltage oscillations in neural populations. Here, we describe two complementary TEMPO (transmembrane electrical measurements performed optically) voltage-sensing technologies that capture neural oscillations up to ∼100 Hz. Fiber-optic TEMPO achieves ∼10-fold greater sensitivity than prior photometric voltage sensing, allows hour-long recordings, and monitors two neuron classes per fiber-optic probe in freely moving mice. With it, we uncovered cross-frequency-coupled theta- and gamma-range oscillations and characterized excitatory-inhibitory neural dynamics during hippocampal ripples and visual cortical processing. The TEMPO mesoscope images voltage activity in two cell classes across an ∼8-mm-wide field of view in head-fixed animals. In awake mice, it revealed sensory-evoked excitatory-inhibitory neural interactions and traveling gamma and 3-7 Hz waves in visual cortex and bidirectional propagation directions for both hippocampal theta and beta waves. These technologies have widespread applications probing diverse oscillations and neuron-type interactions in healthy and diseased brains.
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