Imaging high-frequency voltage dynamics in multiple neuron classes of behaving mammals
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.
Highlights
- Fiber photometry tracks high-frequency neural oscillations in freely moving animals
- Imaging large-scale traveling neural voltage waves in head-restrained behaving animals
- Coupled oscillations of distinct frequencies in specific neuron types of active mice
- Locomotion-evoked hippocampal theta and beta rhythms are bidirectional traveling waves
References
Haziza, S., Chrapkiewicz, R., Zhang, Y., Kruzhilin, V., Li, J., Li, J., … & Schnitzer, M. J. (2025). Imaging high-frequency voltage dynamics in multiple neuron classes of behaving mammals. Cell, 188(16), 4401-4423. https://www.cell.com/cell/fulltext/S0092-8674(25)00730-5