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<p>Electrical signals in neurons underlie perception, movement, memory and behaviour, yet many unfold too rapidly to be captured by conventional optical imaging. Calcium imaging has transformed neuroscience but provides an indirect and relatively slow readout of electrical activity. By directly measuring membrane potential changes, voltage imaging enables millisecond-scale recording of action potentials, subthreshold dynamics and signal propagation across neural circuits. Recent advances in voltage-sensitive dyes and genetically encoded voltage indicators have made voltage imaging increasingly practical, motivating the development of fluorescence microscopy methods optimized for high-speed acquisition. However, voltage imaging remains constrained by trade-offs among imaging speed, spatial resolution, signal-to-noise ratios and photodamage. In this Review we discuss high-speed optical microscopy strategies that address these challenges and highlight the need for co-design among voltage indicators, imaging systems and computational analysis.</p>

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Methods, trade-offs and opportunities in high-speed optical microscopy for neural voltage imaging

  • 期刊论文

  • 发表日期：

    2026年8月3日

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  • Zhaoqiang Wang,
  • Ruth R. Sims,
  • Sheng Xiao,
  • Ruixuan Zhao,
  • Ohr Benshlomo,
  • Zihan Zang,
  • Jiamin Wu,
  • Valentina Emiliani,
  • Liang Gao

摘要

Electrical signals in neurons underlie perception, movement, memory and behaviour, yet many unfold too rapidly to be captured by conventional optical imaging. Calcium imaging has transformed neuroscience but provides an indirect and relatively slow readout of electrical activity. By directly measuring membrane potential changes, voltage imaging enables millisecond-scale recording of action potentials, subthreshold dynamics and signal propagation across neural circuits. Recent advances in voltage-sensitive dyes and genetically encoded voltage indicators have made voltage imaging increasingly practical, motivating the development of fluorescence microscopy methods optimized for high-speed acquisition. However, voltage imaging remains constrained by trade-offs among imaging speed, spatial resolution, signal-to-noise ratios and photodamage. In this Review we discuss high-speed optical microscopy strategies that address these challenges and highlight the need for co-design among voltage indicators, imaging systems and computational analysis.