“High-Speed, Cortex-Wide Volumetric Recording of Neuroactivity at Cellular Resolution Using Light Beads Microscopy” published in Nature Methods

“High-Speed, Cortex-Wide Volumetric Recording of Neuroactivity at Cellular Resolution Using Light Beads Microscopy” published in Nature Methods

News
We are excited to share that our paper entitled “High-Speed, Cortex-Wide Volumetric Recording of Neuroactivity at Cellular Resolution using Light Beads Microscopy” has been published in Nature Methods. 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. This work details our new method Light Beads Microscopy (LBM), which makes use of a column of “Light Beads” – individual beams which are distinguishable in time and focus to different depths in the sample – in order to record from the entire depth range of a given volume within the dead time between…
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High-Speed, Cortex-Wide Volumetric Recording of Neuroactivity at Cellular Resolution Using Light Beads Microscopy

Optical Neurotechnology, Research
Our paper entitled “High-Speed, Cortex-Wide Volumetric Recording of Neuroactivity at Cellular Resolution using Light Beads Microscopy” has been published in Nature Methods. This work details our new method Light Beads Microscopy (LBM) which makes use of a column of “Light Beads” – individual beams which are distinguishable in time and focus to different depths in the sample (Fig. 1a)  – in order to record from the entire depth range of a given volume within the dead time between consecutive pulses from our excitation laser. By combining LBM with a commercial mesoscope, we can image mesoscale and volumetric fields of view (FOVs) at the same rate that a conventional mesoscope records a single plane. As a result, LBM gives optical access to the activity of cortex-wide volumes, allowing recording of up…
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New Article on bioRxiv: High-Speed, Cortex-Wide Volumetric Recording of Neuroactivity at Cellular Resolution using Light Beads Microscopy

New Article on bioRxiv: High-Speed, Cortex-Wide Volumetric Recording of Neuroactivity at Cellular Resolution using Light Beads Microscopy

News, Publications
Excited to share our new manuscript showing volumetric Ca imaging of 1 million neurons across the mouse cortex at cellular resolution using Light Beads Microscopy (LBM). Two-photon microscopy together with genetically encodable calcium indicators has emerged as a standard tool for high-resolution imaging of neuroactivity in scattering brain tissue. However, its various realizations have not overcome the inherent tradeoffs between speed and spatiotemporal sampling in a principled manner which would be necessary to enable, amongst other applications, mesoscale volumetric recording of neuroactivity at cellular resolution and speed compatible with resolving calcium transients. In this paper, we introduce Light Beads Microscopy (LBM), a scalable and spatiotemporally optimal acquisition approach limited only by fluorescence life-time, where a set of axially-separated and temporally-distinct foci record the entire axial imaging range near-simultaneously, enabling volumetric…
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“Neuronal basis of decision making at the single trial level” published in Cell

“Neuronal basis of decision making at the single trial level” published in Cell

Featured, News
Our paper entitled “Cerebellar neurodynamics predict decision timing and outcome on single-trial level” has been published in Cell. In this work we have investigated the neuronal basis of motor planning and decision making at single-trial level, at single-cell resolution and on the level of the whole brain. To study this, we have combined high-speed volumetric calcium imaging based on light-field microscopy (LFM) previously developed in our lab with a new learning paradigm in larval zebrafish for operant conditioning, Relief Of Aversive Stimulus by Turn (ROAST). We have demonstrated that that decision making relies on integration and coordination of information across different brain regions. Within the brain-wide network, we discovered a particularly strong preparatory activity in the cerebellum which allowed us to quantitatively predict both, the time point and the outcome of the…
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Preprint: Cerebellar neurodynamics during motor planning predict decision timing and outcome on single-trial level

Preprint: Cerebellar neurodynamics during motor planning predict decision timing and outcome on single-trial level

Archive, News
We have uploaded a new manuscript entitled "Cerebellar neurodynamics during motor planning predict decision timing and outcome on single-trial level" to the bioRxiv preprint server:The neuronal basis of goal-directed behavior requires interaction of multiple separated brain regions. How subcortical regions and their interactions with brain-wide activity are involved in action selection is less understood. We have investigated this question by developing an assay based on whole-brain volumetric calcium imaging using light-field microscopy combined with an operant-conditioning task in larval zebrafish. We find global and recurring dynamics of brain states to exhibit pre-motor bifurcations towards mutually exclusive decision outcomes which arises from a spatially distributed network. Within this network the cerebellum shows a particularly strong pre-motor activity, predictive of both the timing and outcome of behavior up to ~10 seconds before…
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“HyMS  microscopy” published in Cell

“HyMS microscopy” published in Cell

Featured, News, Publications
Our paper entitled “Volumetric Ca2+ Imaging in the Mouse Brain using Hybrid Multiplexed Sculpted Light (HyMS) Microscopy” has been published in Cell. We have developed a modular platform named Hybrid Multiplexed Sculpted Light (HyMS) microscopy featuring a systems-wide design paradigm that maximizes the acquisition volume size and speed while maintaining fidelity for obtaining single neuron activity traces. Our modular design utilizes a hybrid two- and three-photon acquisition and allows for volumetric recording of neuroactivity at single-cell resolution within up to 1 × 1 × 1.22 mm volumes at up to 17 Hz in awake behaving mice. We establish the capabilities and potential of the different configurations of HyMS microscopy at depth and across brain regions by applying it to in-vivo recording of up to 12,000 neurons in mouse auditory cortex,…
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