New Article on bioRxiv: “Whole-brain neural substrates of behavioral variability in the larval zebrafish”

New Article on bioRxiv: “Whole-brain neural substrates of behavioral variability in the larval zebrafish”

News
We are happy to announce that a new manuscript entitled “Whole-brain neural substrates of behavioral variability in the larval zebrafish” has been uploaded to the bioRxiv preprint server. Animals engaged in naturalistic behavior can exhibit a large degree of behavioral variability even under sensory invariant conditions. Such behavioral variability can include not only variations of the same behavior, but also variability across qualitatively different behaviors driven by divergent cognitive states, such as fight-or-flight decisions. However, the neural circuit mechanisms that generate such divergent behaviors across trials are not well understood. To investigate this question, here we studied the visual-evoked responses of larval zebrafish to moving objects of various sizes, which we found exhibited highly variable and divergent responses across repetitions of the same stimulus.In this work, we present a Fourier…
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New Article on bioRxiv: “A Systematically Optimized Miniaturized Mesoscope (SOMM) for large-scale calcium imaging in freely moving mice”

New Article on bioRxiv: “A Systematically Optimized Miniaturized Mesoscope (SOMM) for large-scale calcium imaging in freely moving mice”

News
We are happy to announce that a new manuscript entitled “A Systematically Optimized Miniaturized Mesoscope (SOMM) for large-scale calcium imaging in freely moving mice” has been uploaded to the bioRxiv preprint server. Understanding how neuronal dynamics gives rise to ethologically relevant behavior requires recording of neuronal population activity via technologies that are compatible with unconstrained animal behavior. However, realizations of cellular resolution head mounted microscopes for mice have been based on conventional microscope designs that feature various forms of ad-hoc miniaturization and weight reduction measures necessary for compatibility with the weight-limits for free animal behavior. As a result, they have typically remained limited to a small field of view (FOV) or low resolution, a shallow depth range and often remain susceptible to motion-induced artifacts. We present a systematically optimized miniaturized…
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New Article on bioRxiv: “Simultaneous, cortex-wide and cellular-resolution neuronal population dynamics reveal an unbounded scaling of dimensionality with neuron number”

New Article on bioRxiv: “Simultaneous, cortex-wide and cellular-resolution neuronal population dynamics reveal an unbounded scaling of dimensionality with neuron number”

News, Publications
We are happy to announce that a new manuscript entitled “Simultaneous, cortex-wide and cellular-resolution neuronal population dynamics reveal an unbounded scaling of dimensionality with neuron number” has been uploaded to the bioRxiv preprint server. The brain’s remarkable properties arise from collective activity of millions of neurons. Widespread application of dimensionality reduction to multi-neuron recordings implies that neural dynamics can be approximated by low-dimensional “latent” signals reflecting neural computations. However, what would be the biological utility of such a redundant and metabolically costly encoding scheme and what is the appropriate resolution and scale of neural recording to understand brain function? Imaging the activity of one million neurons at cellular resolution and near-simultaneously across mouse cortex, we demonstrate an unbounded scaling of dimensionality with neuron number. While half of the neural variance…
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“Mesoscale volumetric light-field (MesoLF) imaging of neuroactivity across cortical areas at 18 Hz” published in Nature Methods

“Mesoscale volumetric light-field (MesoLF) imaging of neuroactivity across cortical areas at 18 Hz” published in Nature Methods

News, Publications
Our article entitled “Mesoscale volumetric light field (MesoLF) imaging of neuroactivity across cortical areas at 18 Hz” has been published in Nature Methods. Information flow across mesoscale, i.e., multi-millimeter-sized regions of the mammalian cortex is a key feature of high-level cognition and is known to underlie complex behaviors. Yet, tracing this information flow in a volumetric fashion at a cellular resolution and high speed has remained challenging. This is primarily because most established neuronal activity imaging methods, such as two-photon microscopy, rely on time-consuming point-by-point scanning of an excitation beam focus to read out neuronal activity, as reported by the fluorescence rate of designer proteins known as genetically encoded calcium indicators (GECIs). We present a modular, mesoscale light field (MesoLF) imaging hardware and software solution that allows recording from thousands of…
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“Dynamic Processing of Hunger and Thirst by Common Mesolimbic Neural Ensembles” published in PNAS

“Dynamic Processing of Hunger and Thirst by Common Mesolimbic Neural Ensembles” published in PNAS

News
We are happy to share that our paper "Dynamic Processing of Hunger and Thirst by Common Mesolimbic Neural Ensembles" has been published in PNAS. Eating and drinking both activate a subset of accumbal neurons but it was unknown whether same or different neurons represent distinct need states. We set out to study the state-coding principles of hunger and thirst in the nucleus accumbens (NAc) using two-photon calcium imaging of neural activity in awake mice during feeding and drinking. We find that highly overlapping sets of individual D1 and D2 neurons respond similarly to food and water with specific subsets showing distinct temporal activity patterns throughout the consummatory phase. Modulating D1 and D2 neurons elicited analogous effects on both behavioral programs. These data suggest a general role of NAc to regulate…
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“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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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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