Open AccessHigh-speed, cortex-wide volumetric recording of neuroactivity at cellular resolution using light beads microscopy
Author(s) -
Jeff Demas,
Jason Manley,
Frank Tejera,
Kevin M. Barber,
Hyewon Kim,
Francisca Martínez Traub,
Brandon Chen,
Alipasha Vaziri
Publication year - 2021
Publication title -
nature methods
Language(s) - English
Resource type - Journals
SCImago Journal Rank - 19.469
H-Index - 318
eISSN - 1548-7105
pISSN - 1548-7091
DOI - 10.1038/s41592-021-01239-8
Subject(s) - voxel , microscopy , mesoscopic physics , resolution (logic) , materials science , cortex (anatomy) , image resolution , temporal resolution , fluorescence microscope , optics , biomedical engineering , biological system , fluorescence , computer science , physics , neuroscience , artificial intelligence , biology , medicine , quantum mechanics
Two-photon microscopy has enabled high-resolution imaging of neuroactivity at depth within scattering brain tissue. However, its various realizations have not overcome the tradeoffs between speed and spatiotemporal sampling that would be necessary to enable mesoscale volumetric recording of neuroactivity at cellular resolution and speed compatible with resolving calcium transients. Here, we introduce light beads microscopy (LBM), a scalable and spatiotemporally optimal acquisition approach limited only by fluorescence lifetime, where a set of axially separated and temporally distinct foci record the entire axial imaging range near-simultaneously, enabling volumetric recording at 1.41 × 10 8 voxels per second. Using LBM, we demonstrate mesoscopic and volumetric imaging at multiple scales in the mouse cortex, including cellular-resolution recordings within ~3 × 5 × 0.5 mm volumes containing >200,000 neurons at ~5 Hz and recordings of populations of ~1 million neurons within ~5.4 × 6 × 0.5 mm volumes at ~2 Hz, as well as higher speed (9.6 Hz) subcellular-resolution volumetric recordings. LBM provides an opportunity for discovering the neurocomputations underlying cortex-wide encoding and processing of information in the mammalian brain.