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      Unsupervised discovery of temporal sequences in high-dimensional datasets, with applications to neuroscience

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          Abstract

          Identifying low-dimensional features that describe large-scale neural recordings is a major challenge in neuroscience. Repeated temporal patterns (sequences) are thought to be a salient feature of neural dynamics, but are not succinctly captured by traditional dimensionality reduction techniques. Here, we describe a software toolbox—called seqNMF—with new methods for extracting informative, non-redundant, sequences from high-dimensional neural data, testing the significance of these extracted patterns, and assessing the prevalence of sequential structure in data. We test these methods on simulated data under multiple noise conditions, and on several real neural and behavioral datas. In hippocampal data, seqNMF identifies neural sequences that match those calculated manually by reference to behavioral events. In songbird data, seqNMF discovers neural sequences in untutored birds that lack stereotyped songs. Thus, by identifying temporal structure directly from neural data, seqNMF enables dissection of complex neural circuits without relying on temporal references from stimuli or behavioral outputs.

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          Most cited references50

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          Fully integrated silicon probes for high-density recording of neural activity

          Sensory, motor and cognitive operations involve the coordinated action of large neuronal populations across multiple brain regions in both superficial and deep structures. Existing extracellular probes record neural activity with excellent spatial and temporal (sub-millisecond) resolution, but from only a few dozen neurons per shank. Optical Ca2+ imaging offers more coverage but lacks the temporal resolution needed to distinguish individual spikes reliably and does not measure local field potentials. Until now, no technology compatible with use in unrestrained animals has combined high spatiotemporal resolution with large volume coverage. Here we design, fabricate and test a new silicon probe known as Neuropixels to meet this need. Each probe has 384 recording channels that can programmably address 960 complementary metal–oxide–semiconductor (CMOS) processing-compatible low-impedance TiN sites that tile a single 10-mm long, 70 × 20-μm cross-section shank. The 6 × 9-mm probe base is fabricated with the shank on a single chip. Voltage signals are filtered, amplified, multiplexed and digitized on the base, allowing the direct transmission of noise-free digital data from the probe. The combination of dense recording sites and high channel count yielded well-isolated spiking activity from hundreds of neurons per probe implanted in mice and rats. Using two probes, more than 700 well-isolated single neurons were recorded simultaneously from five brain structures in an awake mouse. The fully integrated functionality and small size of Neuropixels probes allowed large populations of neurons from several brain structures to be recorded in freely moving animals. This combination of high-performance electrode technology and scalable chip fabrication methods opens a path towards recording of brain-wide neural activity during behaviour.
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            Choice-specific sequences in parietal cortex during a virtual-navigation decision task

            The posterior parietal cortex (PPC) plays an important role in many cognitive behaviors; however, the neural circuit dynamics underlying PPC function are not well understood. Here we optically imaged the spatial and temporal activity patterns of neuronal populations in mice performing a PPC-dependent task that combined a perceptual decision and memory-guided navigation in a virtual environment. Individual neurons had transient activation staggered relative to one another in time, forming a sequence of neuronal activation spanning the entire length of a task trial. Distinct sequences of neurons were triggered on trials with opposite behavioral choices and defined divergent, choice-specific trajectories through a state space of neuronal population activity. Cells participating in the different sequences and at distinct time points in the task were anatomically intermixed over microcircuit length scales (< 100 micrometers). During working memory decision tasks the PPC may therefore perform computations through sequence-based circuit dynamics, rather than long-lived stable states, implemented using anatomically intermingled microcircuits.
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              Behavior-dependent short-term assembly dynamics in the medial prefrontal cortex.

              Although short-term plasticity is believed to play a fundamental role in cortical computation, empirical evidence bearing on its role during behavior is scarce. Here we looked for the signature of short-term plasticity in the fine-timescale spiking relationships of a simultaneously recorded population of physiologically identified pyramidal cells and interneurons, in the medial prefrontal cortex of the rat, in a working memory task. On broader timescales, sequentially organized and transiently active neurons reliably differentiated between different trajectories of the rat in the maze. On finer timescales, putative monosynaptic interactions reflected short-term plasticity in their dynamic and predictable modulation across various aspects of the task, beyond a statistical accounting for the effect of the neurons' co-varying firing rates. Seeking potential mechanisms for such effects, we found evidence for both firing pattern-dependent facilitation and depression, as well as for a supralinear effect of presynaptic coincidence on the firing of postsynaptic targets.
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                Author and article information

                Contributors
                Role: Reviewing Editor
                Role: Senior Editor
                Journal
                eLife
                Elife
                eLife
                eLife
                eLife Sciences Publications, Ltd
                2050-084X
                05 February 2019
                2019
                : 8
                : e38471
                Affiliations
                [1 ]deptMcGovern Institute for Brain Research, Department of Brain and Cognitive Sciences Massachusetts Institute of Technology CambridgeUnited States
                [2 ]deptNeurosciences Program Stanford University StanfordUnited States
                [3 ]deptSchool of Life Sciences and Technology ShanghaiTech University ShanghaiChina
                [4 ]deptCenter for Neuroscience, Department of Neurobiology, Physiology and Behavior University of California, Davis DavisUnited States
                [5 ]deptDepartment of Ophthamology and Vision Science University of California, Davis DavisUnited States
                The University of Texas at Austin United States
                University of Oxford United Kingdom
                The University of Texas at Austin United States
                Author notes
                [†]

                These authors contributed equally to this work.

                Author information
                http://orcid.org/0000-0001-6593-4398
                http://orcid.org/0000-0003-0567-7195
                https://orcid.org/0000-0001-5853-103X
                http://orcid.org/0000-0001-6257-5756
                http://orcid.org/0000-0002-8257-2314
                http://orcid.org/0000-0001-7539-1745
                Article
                38471
                10.7554/eLife.38471
                6363393
                30719973
                46d6520a-e713-4c35-900e-9f57c9958134
                © 2019, Mackevicius et al

                This article is distributed under the terms of the Creative Commons Attribution License, which permits unrestricted use and redistribution provided that the original author and source are credited.

                History
                : 19 May 2018
                : 04 January 2019
                Funding
                Funded by: FundRef http://dx.doi.org/10.13039/100000893, Simons Foundation;
                Award ID: Simons Collaboration for the Global Brain
                Award Recipient :
                Funded by: FundRef http://dx.doi.org/10.13039/100000055, National Institute on Deafness and Other Communication Disorders;
                Award ID: R01 DC009183
                Award Recipient :
                Funded by: FundRef http://dx.doi.org/10.13039/100001229, G Harold and Leila Y. Mathers Foundation;
                Award Recipient :
                Funded by: FundRef http://dx.doi.org/10.13039/100000005, U.S. Department of Defense;
                Award ID: NDSEG Fellowship program
                Award Recipient :
                Funded by: FundRef http://dx.doi.org/10.13039/100004944, Department of Energy, Labor and Economic Growth;
                Award ID: Computational Science Graduate Fellowship (CSGF)
                Award Recipient :
                Funded by: FundRef http://dx.doi.org/10.13039/100000052, NIH Office of the Director;
                Award ID: Training Grant 5T32EB019940-03
                Award Recipient :
                Funded by: FundRef http://dx.doi.org/10.13039/100000065, National Institute of Neurological Disorders and Stroke;
                Award ID: U19 NS104648
                Award Recipient :
                Funded by: FundRef http://dx.doi.org/10.13039/100000025, National Institute of Mental Health;
                Award ID: R25 MH062204
                Award Recipient :
                The funders had no role in study design, data collection and interpretation, or the decision to submit the work for publication.
                Categories
                Tools and Resources
                Neuroscience
                Custom metadata
                Building on simple unsupervised matrix factorization techniques, the seqNMF algorithm successfully recovers neural sequences in a wide range of simulated and real datasets.

                Life sciences
                zebra finch,sequence,matrix factorization,unsupervised,rat,other
                Life sciences
                zebra finch, sequence, matrix factorization, unsupervised, rat, other

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