Faculty Opinions recommendation of Imaging large-scale neural activity with cellular resolution in awake, mobile mice.

The advent of methods for optical imaging of large-scale neural activity at cellular resolution in behaving animals presents the problem of identifying behavior-encoding cells within the resulting image time series. Rapid and precise identification of cells with particular neural encoding would facilitate targeted activity measurements and perturbations useful in characterizing the operating principles of neural circuits. Here we report a regression-based approach to semiautomatically identify neurons that is based on the correlation of fluorescence time series with quantitative measurements of behavior. The approach is illustrated with a novel preparation allowing synchronous eye tracking and two-photon laser scanning fluorescence imaging of calcium changes in populations of hindbrain neurons during spontaneous eye movement in the larval zebrafish. Putative velocity-to-position oculomotor integrator neurons were identified that showed a broad spatial distribution and diversity of encoding. Optical identification of integrator neurons was confirmed with targeted loose-patch electrical recording and laser ablation. The general regression-based approach we demonstrate should be widely applicable to calcium imaging time series in behaving animals.

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Large-scale cellular-resolution imaging of neural activity in freely behaving mice

10.1101/2021.01.15.426462 ◽

2021 ◽

Author(s):

D.P. Leman ◽

I.A. Chen ◽

K.A. Bolding ◽

J. Tai ◽

L.K. Wilmerding ◽

...

Keyword(s):

Neural Activity ◽

Large Scale ◽

First Generation ◽

Brain Regions ◽

Field Of View ◽

Cellular Resolution ◽

Neural Populations ◽

Resolution Imaging ◽

Freely Behaving ◽

Freely Moving

AbstractMiniaturized microscopes for head-mounted fluorescence imaging are powerful tools for visualizing neural activity during naturalistic behaviors, but the restricted field of view of first-generation ‘miniscopes’ limits the size of neural populations accessible for imaging. Here we describe a novel miniaturized mesoscope offering cellular-resolution imaging over areas spanning several millimeters in freely moving mice. This system enables comprehensive visualization of activity across entire brain regions or interactions across areas.

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Imaging Large-Scale Neural Activity with Cellular Resolution in Awake, Mobile Mice

Neuron ◽

10.1016/j.neuron.2007.08.003 ◽

2007 ◽

Vol 56 (1) ◽

pp. 43-57 ◽

Cited By ~ 625

Author(s):

Daniel A. Dombeck ◽

Anton N. Khabbaz ◽

Forrest Collman ◽

Thomas L. Adelman ◽

David W. Tank

Keyword(s):

Neural Activity ◽

Large Scale ◽

Cellular Resolution

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Dynamic relationships between spontaneous and evoked electrophysiological activity

Communications Biology ◽

10.1038/s42003-021-02240-9 ◽

2021 ◽

Vol 4 (1) ◽

Author(s):

Soren Wainio-Theberge ◽

Annemarie Wolff ◽

Georg Northoff

Keyword(s):

Neural Activity ◽

Large Scale ◽

Behavioral Outcomes ◽

Low Frequencies ◽

Scale Free ◽

Non Invasive ◽

Spontaneous Neural Activity ◽

Electrophysiological Signals ◽

Evoked Activity ◽

Dynamic Relationships

AbstractSpontaneous neural activity fluctuations have been shown to influence trial-by-trial variation in perceptual, cognitive, and behavioral outcomes. However, the complex electrophysiological mechanisms by which these fluctuations shape stimulus-evoked neural activity remain largely to be explored. Employing a large-scale magnetoencephalographic dataset and an electroencephalographic replication dataset, we investigate the relationship between spontaneous and evoked neural activity across a range of electrophysiological variables. We observe that for high-frequency activity, high pre-stimulus amplitudes lead to greater evoked desynchronization, while for low frequencies, high pre-stimulus amplitudes induce larger degrees of event-related synchronization. We further decompose electrophysiological power into oscillatory and scale-free components, demonstrating different patterns of spontaneous-evoked correlation for each component. Finally, we find correlations between spontaneous and evoked time-domain electrophysiological signals. Overall, we demonstrate that the dynamics of multiple electrophysiological variables exhibit distinct relationships between their spontaneous and evoked activity, a result which carries implications for experimental design and analysis in non-invasive electrophysiology.

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Connectome to behaviour: modelling Caenorhabditis elegans at cellular resolution

Philosophical Transactions of the Royal Society B Biological Sciences ◽

10.1098/rstb.2017.0366 ◽

2018 ◽

Vol 373 (1758) ◽

pp. 20170366 ◽

Cited By ~ 1

Author(s):

Stephen D. Larson ◽

Padraig Gleeson ◽

André E. X. Brown

Keyword(s):

Caenorhabditis Elegans ◽

Neural Activity ◽

Multiscale Simulations ◽

Theme Issue ◽

Wiring Diagram ◽

C Elegans ◽

Behaviour Modelling ◽

Cellular Resolution ◽

The Mind

It has been 30 years since the ‘mind of the worm’ was published in Philosophical Transactions B (White et al . 1986 Phil. Trans. R. Soc. Lond. B 314 , 1–340). Predicting Caenorhabditis elegans ' behaviour from its wiring diagram has been an enduring challenge since then. This special theme issue of Philosophical Transactions B combines research from neuroscientists, physicists, mathematicians and engineers to discuss advances in neural activity imaging, behaviour quantification and multiscale simulations, and how they are bringing the goal of whole-animal modelling at cellular resolution within reach. This article is part of a discussion meeting issue ‘Connectome to behaviour: modelling C. elegans at cellular resolution’.

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A very large-scale microelectrode array for cellular-resolution electrophysiology

Nature Communications ◽

10.1038/s41467-017-02009-x ◽

2017 ◽

Vol 8 (1) ◽

Cited By ~ 46

Author(s):

David Tsai ◽

Daniel Sawyer ◽

Adrian Bradd ◽

Rafael Yuste ◽

Kenneth L. Shepard

Keyword(s):

Large Scale ◽

Microelectrode Array ◽

Cellular Resolution

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All-optical imaging and patterned stimulation with a one-photon endoscope

10.1101/2021.12.19.473349 ◽

2021 ◽

Author(s):

Jinyong Zhang ◽

Ryan N Hughes ◽

Namsoo Kim ◽

Isabella P Fallon ◽

Konstantin I bakhurin ◽

...

Keyword(s):

Neural Activity ◽

Calcium Imaging ◽

Neural Circuit ◽

Integrated System ◽

Striatal Neurons ◽

Indirect Pathway ◽

Cellular Resolution ◽

All Optical ◽

Freely Moving

While in vivo calcium imaging makes it possible to record activity in defined neuronal populations with cellular resolution, optogenetics allows selective manipulation of neural activity. Recently, these two tools have been combined to stimulate and record neural activity at the same time, but current approaches often rely on two-photon microscopes that are difficult to use in freely moving animals. To address these limitations, we have developed a new integrated system combining a one-photon endoscope and a digital micromirror device for simultaneous calcium imaging and precise optogenetic photo-stimulation with near cellular resolution (Miniscope with All-optical Patterned Stimulation and Imaging, MAPSI). Using this highly portable system in freely moving mice, we were able to image striatal neurons from either the direct pathway or the indirect pathway while simultaneously activating any neuron of choice in the field of view, or to synthesize arbitrary spatiotemporal patterns of photo-stimulation. We could also select neurons based on their relationship with behavior and recreate the behavior by mimicking the natural neural activity with photo-stimulation. MAPSI thus provides a powerful tool for interrogation of neural circuit function in freely moving animals.

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Multi-plane Imaging of Neural Activity From the Mammalian Brain Using a Fast-switching Liquid Crystal Spatial Light Modulator

10.1101/506618 ◽

2018 ◽

Cited By ~ 2

Author(s):

Rui Liu ◽

Neil Ball ◽

James Brockill ◽

Leonard Kuan ◽

Daniel Millman ◽

...

Keyword(s):

Liquid Crystal ◽

Neural Activity ◽

Spatial Light Modulator ◽

Large Scale ◽

Striate Cortex ◽

Mammalian Brain ◽

Light Modulator ◽

Fast Switching ◽

Large Populations ◽

Two Photon Fluorescence

We report a novel two-photon fluorescence microscope based on a fast-switching liquid crystal spatial light modulator and a pair of galvo-resonant scanners for large-scale recording of neural activity from the mammalian brain. The utilized imaging technique is capable of monitoring large populations of neurons spread across different layers of the neocortex in awake and behaving mice. During each imaging session, all visual stimulus driven somatic activity could be recorded in the same behavior state. We observed heterogeneous response to different types of visual stimuli from ~ 3,300 excitatory neurons reaching from layer II/III to V of the striate cortex.

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Cellular-resolution gene expression profiling in the neonatal marmoset brain reveals dynamic species- and region-specific differences

Proceedings of the National Academy of Sciences ◽

10.1073/pnas.2020125118 ◽

2021 ◽

Vol 118 (18) ◽

pp. e2020125118

Author(s):

Yoshiaki Kita ◽

Hirozumi Nishibe ◽

Yan Wang ◽

Tsutomu Hashikawa ◽

Satomi S. Kikuchi ◽

...

Keyword(s):

Gene Expression ◽

Gene Expression Profiling ◽

Expression Profiling ◽

Large Scale ◽

Molecular Mechanisms ◽

Neural Circuit ◽

Expression Patterns ◽

Three Dimensional ◽

Control Of Gene Expression ◽

Cellular Resolution

Precise spatiotemporal control of gene expression in the developing brain is critical for neural circuit formation, and comprehensive expression mapping in the developing primate brain is crucial to understand brain function in health and disease. Here, we developed an unbiased, automated, large-scale, cellular-resolution in situ hybridization (ISH)–based gene expression profiling system (GePS) and companion analysis to reveal gene expression patterns in the neonatal New World marmoset cortex, thalamus, and striatum that are distinct from those in mice. Gene-ontology analysis of marmoset-specific genes revealed associations with catalytic activity in the visual cortex and neuropsychiatric disorders in the thalamus. Cortically expressed genes with clear area boundaries were used in a three-dimensional cortical surface mapping algorithm to delineate higher-order cortical areas not evident in two-dimensional ISH data. GePS provides a powerful platform to elucidate the molecular mechanisms underlying primate neurobiology and developmental psychiatric and neurological disorders.

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Large- and multi-scale networks in the rodent brain during novelty exploration

10.1101/2020.12.08.416248 ◽

2020 ◽

Author(s):

Michael X Cohen ◽

Bernhard Englitz ◽

Arthur S C França

Keyword(s):

Prefrontal Cortex ◽

Parietal Cortex ◽

Local Field ◽

Neural Activity ◽

Large Scale ◽

Field Potential ◽

Brain Regions ◽

Data Availability ◽

Data Matrix ◽

Temporal Scales

AbstractNeural activity is coordinated across multiple spatial and temporal scales, and these patterns of coordination are implicated in both healthy and impaired cognitive operations. However, empirical cross-scale investigations are relatively infrequent, due to limited data availability and to the difficulty of analyzing rich multivariate datasets. Here we applied frequency-resolved multivariate source-separation analyses to characterize a large-scale dataset comprising spiking and local field potential activity recorded simultaneously in three brain regions (prefrontal cortex, parietal cortex, hippocampus) in freely-moving mice. We identified a constellation of multidimensional, inter-regional networks across a range of frequencies (2-200 Hz). These networks were reproducible within animals across different recording sessions, but varied across different animals, suggesting individual variability in network architecture. The theta band (~4-10 Hz) networks had several prominent features, including roughly equal contribution from all regions and strong inter-network synchronization. Overall, these findings demonstrate a multidimensional landscape of large-scale functional activations of cortical networks operating across multiple spatial, spectral, and temporal scales during open-field exploration.Significance statementNeural activity is synchronized over space, time, and frequency. To characterize the dynamics of large-scale networks spanning multiple brain regions, we recorded data from the prefrontal cortex, parietal cortex, and hippocampus in awake behaving mice, and pooled data from spiking activity and local field potentials into one data matrix. Frequency-specific multivariate decomposition methods revealed a cornucopia of neural networks defined by coherent spatiotemporal patterns over time. These findings reveal a rich, dynamic, and multivariate landscape of large-scale neural activity patterns during foraging behavior.

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