A structured-illumination miniscope for optically sectioned imaging and real-time neural decoding

Authors

Lin, H., Wang, S., Zhu, Y., Yin, Z., Guo, Q., Zhou, J.

Abstract

Single-photon miniscopes enable large-scale calcium imaging in freely behaving animals but are limited by out-of-focus background fluorescence that degrades image contrast and single-cell signal fidelity. Multiphoton approaches address this limitation but remain costly and complex. Here we introduce a lightweight (<3 g), low-cost structured illumination miniscope that achieves optical sectioning in freely behaving mice. Using HiLo imaging implemented with a simple Ronchi grating and time-multiplexed excitation, the system strongly suppresses background fluorescence while preserving the speed, field of view, and accessibility of widefield miniscopes, and supports optical-sectioned multi-plane imaging to increase neuronal yield. Using hippocampal recordings, we show enhanced region-of-interest (ROI)-based signal quality and spatial information readout, allowing simple ROI-averaged signals to approach the performance of offline algorithm-extracted signals. We further demonstrate a proof-of-principle closed-loop brain--machine interface enabled by rapid online signal extraction and real-time neural decoding. Together, these results establish structured illumination as a practical and accessible strategy for achieving high-contrast calcium imaging with miniaturized microscopes.

Preprint server: bioRxiv
The authors list and abstract were imported from bioRxiv on 20 Jul 2026.

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