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15 Janelia Publications

Showing 1-10 of 15 results
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    09/02/21 | Electrode pooling can boost the yield of extracellular recordings with switchable silicon probes.
    Lee KH, Ni Y, Colonell J, Karsh B, Putzeys J, Pachitariu M, Harris TD, Meister M
    Nature Communications. 2021 Sep 02;12(1):5245. doi: 10.1038/s41467-021-25443-4

    State-of-the-art silicon probes for electrical recording from neurons have thousands of recording sites. However, due to volume limitations there are typically many fewer wires carrying signals off the probe, which restricts the number of channels that can be recorded simultaneously. To overcome this fundamental constraint, we propose a method called electrode pooling that uses a single wire to serve many recording sites through a set of controllable switches. Here we present the framework behind this method and an experimental strategy to support it. We then demonstrate its feasibility by implementing electrode pooling on the Neuropixels 1.0 electrode array and characterizing its effect on signal and noise. Finally we use simulations to explore the conditions under which electrode pooling saves wires without compromising the content of the recordings. We make recommendations on the design of future devices to take advantage of this strategy.

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    07/01/21 | Hunger or thirst state uncertainty is resolved by outcome evaluation in medial prefrontal cortex to guide decision-making.
    Eiselt A, Chen S, Chen J, Arnold J, Kim T, Pachitariu M, Sternson SM
    Nature Neuroscience. 2021 Jul 01;24(7):907-912. doi: 10.1038/s41593-021-00850-4

    Physiological need states direct decision-making toward re-establishing homeostasis. Using a two-alternative forced choice task for mice that models elements of human decisions, we found that varying hunger and thirst states caused need-inappropriate choices, such as food seeking when thirsty. These results show limits on interoceptive knowledge of hunger and thirst states to guide decision-making. Instead, need states were identified after food and water consumption by outcome evaluation, which depended on the medial prefrontal cortex.

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    05/13/21 | High-precision coding in visual cortex.
    Stringer C, Michaelos M, Tsyboulski D, Lindo SE, Pachitariu M
    Cell. 2021 May 13;184(10):2767-78. doi: 10.1016/j.cell.2021.03.042

    Individual neurons in visual cortex provide the brain with unreliable estimates of visual features. It is not known whether the single-neuron variability is correlated across large neural populations, thus impairing the global encoding of stimuli. We recorded simultaneously from up to 50,000 neurons in mouse primary visual cortex (V1) and in higher order visual areas and measured stimulus discrimination thresholds of 0.35° and 0.37°, respectively, in an orientation decoding task. These neural thresholds were almost 100 times smaller than the behavioral discrimination thresholds reported in mice. This discrepancy could not be explained by stimulus properties or arousal states. Furthermore, behavioral variability during a sensory discrimination task could not be explained by neural variability in V1. Instead, behavior-related neural activity arose dynamically across a network of non-sensory brain areas. These results imply that perceptual discrimination in mice is limited by downstream decoders, not by neural noise in sensory representations.

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    04/16/21 | Neuropixels 2.0: A miniaturized high-density probe for stable, long-term brain recordings.
    Steinmetz NA, Aydın Ç, Lebedeva A, Okun M, Pachitariu M, Bauza M, Beau M, Bhagat J, Böhm C, Broux M, Chen S, Colonell J, Gardner RJ, Karsh B, Kloosterman F, Kostadinov D, Mora-Lopez C, O'Callaghan J, Park J, Putzeys J, Sauerbrei B, van Daal RJ, Vollan AZ, Wang S, Welkenhuysen M, Ye Z, Dudman JT, Dutta B, Hantman AW, Harris KD, Lee AK, Moser EI, O'Keefe J, Renart A, Svoboda K, Häusser M, Haesler S, Carandini M, Harris TD
    Science. 2021 Apr 16;372(6539):. doi: 10.1126/science.abf4588

    Measuring the dynamics of neural processing across time scales requires following the spiking of thousands of individual neurons over milliseconds and months. To address this need, we introduce the Neuropixels 2.0 probe together with newly designed analysis algorithms. The probe has more than 5000 sites and is miniaturized to facilitate chronic implants in small mammals and recording during unrestrained behavior. High-quality recordings over long time scales were reliably obtained in mice and rats in six laboratories. Improved site density and arrangement combined with newly created data processing methods enable automatic post hoc correction for brain movements, allowing recording from the same neurons for more than 2 months. These probes and algorithms enable stable recordings from thousands of sites during free behavior, even in small animals such as mice.

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    01/20/21 | Survey of spiking in the mouse visual system reveals functional hierarchy.
    Siegle JH, Jia X, Durand S, Gale S, Bennett C, Graddis N, Heller G, Ramirez TK, Choi H, Luviano JA, Groblewski PA, Ahmed R, Arkhipov A, Bernard A, Billeh YN, Brown D, Buice MA, Cain N, Caldejon S, Casal L, Cho A, Chvilicek M, Cox TC, Dai K, Denman DJ, de Vries SE, Dietzman R, Esposito L, Farrell C, Feng D, Galbraith J, Garrett M, Gelfand EC, Hancock N, Harris JA, Howard R, Hu B, Hytnen R, Iyer R, Jessett E, Johnson K, Kato I, Kiggins J, Lambert S, Lecoq J, Ledochowitsch P, Lee JH, Leon A, Li Y, Liang E, Long F, Mace K, Melchior J, Millman D, Mollenkopf T, Nayan C, Ng L, Ngo K, Nguyen T, Nicovich PR, North K, Ocker GK, Ollerenshaw D, Oliver M, Pachitariu M, Perkins J, Reding M, Reid D, Robertson M, Ronellenfitch K, Seid S, Slaughterbeck C, Stoecklin M, Sullivan D, Sutton B, Swapp J, Thompson C, Turner K, Wakeman W, Whitesell JD, Williams D, Williford A, Young R, Zeng H, Naylor S, Phillips JW, Reid RC, Mihalas S, Olsen SR, Koch C
    Nature. 2021 Jan 20;592(7852):86-92(7852):86-92. doi: 10.1038/s41586-020-03171-x

    The anatomy of the mammalian visual system, from the retina to the neocortex, is organized hierarchically. However, direct observation of cellular-level functional interactions across this hierarchy is lacking due to the challenge of simultaneously recording activity across numerous regions. Here we describe a large, open dataset-part of the Allen Brain Observatory-that surveys spiking from tens of thousands of units in six cortical and two thalamic regions in the brains of mice responding to a battery of visual stimuli. Using cross-correlation analysis, we reveal that the organization of inter-area functional connectivity during visual stimulation mirrors the anatomical hierarchy from the Allen Mouse Brain Connectivity Atlas. We find that four classical hierarchical measures-response latency, receptive-field size, phase-locking to drifting gratings and response decay timescale-are all correlated with the hierarchy. Moreover, recordings obtained during a visual task reveal that the correlation between neural activity and behavioural choice also increases along the hierarchy. Our study provides a foundation for understanding coding and signal propagation across hierarchically organized cortical and thalamic visual areas.

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    01/07/21 | Cellpose: a generalist algorithm for cellular segmentation.
    Stringer C, Wang T, Michaelos M, Pachitariu M
    Nature Methods. 2021 Jan 07;18(1):100-106. doi: 10.1038/s41592-020-01018-x

    Many biological applications require the segmentation of cell bodies, membranes and nuclei from microscopy images. Deep learning has enabled great progress on this problem, but current methods are specialized for images that have large training datasets. Here we introduce a generalist, deep learning-based segmentation method called Cellpose, which can precisely segment cells from a wide range of image types and does not require model retraining or parameter adjustments. Cellpose was trained on a new dataset of highly varied images of cells, containing over 70,000 segmented objects. We also demonstrate a three-dimensional (3D) extension of Cellpose that reuses the two-dimensional (2D) model and does not require 3D-labeled data. To support community contributions to the training data, we developed software for manual labeling and for curation of the automated results. Periodically retraining the model on the community-contributed data will ensure that Cellpose improves constantly.

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    08/01/20 | Arousal modulates retinal output.
    Schröder S, Steinmetz NA, Krumin M, Pachitariu M, Rizzi M, Lagnado L, Harris KD, Carandini M
    Neuron. 2020 Aug 01;107(3):487. doi: 10.1016/j.neuron.2020.04.026

    At various stages of the visual system, visual responses are modulated by arousal. Here, we find that in mice this modulation operates as early as in the first synapse from the retina and even in retinal axons. To measure retinal activity in the awake, intact brain, we imaged the synaptic boutons of retinal axons in the superior colliculus. Their activity depended not only on vision but also on running speed and pupil size, regardless of retinal illumination. Arousal typically reduced their visual responses and selectivity for direction and orientation. Recordings from retinal axons in the optic tract revealed that arousal modulates the firing of some retinal ganglion cells. Arousal had similar effects postsynaptically in colliculus neurons, independent of activity in the other main source of visual inputs to the colliculus, the primary visual cortex. These results indicate that arousal modulates activity at every stage of the mouse visual system.

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    02/03/20 | Cellpose: a generalist algorithm for cellular segmentation
    Stringer C, Michaelos M, Pachitariu M
    bioRxiv. 2020 Feb 03:. doi: 10.1101/2020.02.02.931238

    Many biological applications require the segmentation of cell bodies, membranes and nuclei from microscopy images. Deep learning has enabled great progress on this problem, but current methods are specialized for images that have large training datasets. Here we introduce a generalist, deep learning-based segmentation algorithm called Cellpose, which can very precisely segment a wide range of image types out-of-the-box and does not require model retraining or parameter adjustments. We trained Cellpose on a new dataset of highly-varied images of cells, containing over 70,000 segmented objects. To support community contributions to the training data, we developed software for manual labelling and for curation of the automated results, with optional direct upload to our data repository. Periodically retraining the model on the community-contributed data will ensure that Cellpose improves constantly.

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    06/26/19 | High-dimensional geometry of population responses in visual cortex.
    Stringer C, Pachitariu M, Steinmetz NA, Carandini M, Harris KD
    Nature. 2019 Jun 26;571(7765):361-65. doi: 10.1038/s41586-019-1346-5

    A neuronal population encodes information most efficiently when its activity is uncorrelated and high-dimensional, and most robustly when its activity is correlated and lower-dimensional. Here, we analyzed the correlation structure of natural image coding, in large visual cortical populations recorded from awake mice. Evoked population activity was high dimensional, with correlations obeying an unexpected power-law: the n-th principal component variance scaled as 1/n. This was not inherited from the 1/f spectrum of natural images, because it persisted after stimulus whitening. We proved mathematically that the variance spectrum must decay at least this fast if a population code is smooth, i.e. if small changes in input cannot dominate population activity. The theory also predicts larger power-law exponents for lower-dimensional stimulus ensembles, which we validated experimentally. These results suggest that coding smoothness represents a fundamental constraint governing correlations in neural population codes.

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    04/19/19 | Spontaneous behaviors drive multidimensional, brain-wide population activity.
    Stringer C, Pachitariu M, Steinmetz NA, Reddy CB, Carandini M, Harris KD
    Science. 2019 Apr 18;364(6437):255. doi: 10.1101/306019

    Sensory cortices are active in the absence of external sensory stimuli. To understand the nature of this ongoing activity, we used two-photon calcium imaging to record from over 10,000 neurons in the visual cortex of mice awake in darkness while monitoring their behavior videographically. Ongoing population activity was multidimensional, exhibiting at least 100 significant dimensions, some of which were related to the spontaneous behaviors of the mice. The largest single dimension was correlated with the running speed and pupil area, while a 16-dimensional summary of orofacial behaviors could predict ~45% of the explainable neural variance. Electrophysiological recordings with 8 simultaneous Neuropixels probes revealed a similar encoding of high-dimensional orofacial behaviors across multiple forebrain regions. Representation of motor variables continued uninterrupted during visual stimulus presentation, occupying dimensions nearly orthogonal to the stimulus responses. Our results show that a multidimensional representation of motor state is encoded across the forebrain, and is integrated with visual input by neuronal populations in primary visual cortex.

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