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      Non-linear dimensionality reduction on extracellular waveforms reveals cell type diversity in premotor cortex

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          Abstract

          Cortical circuits are thought to contain a large number of cell types that coordinate to produce behavior. Current in vivo methods rely on clustering of specified features of extracellular waveforms to identify putative cell types, but these capture only a small amount of variation. Here, we develop a new method ( WaveMAP) that combines non-linear dimensionality reduction with graph clustering to identify putative cell types. We apply WaveMAP to extracellular waveforms recorded from dorsal premotor cortex of macaque monkeys performing a decision-making task. Using WaveMAP, we robustly establish eight waveform clusters and show that these clusters recapitulate previously identified narrow- and broad-spiking types while revealing previously unknown diversity within these subtypes. The eight clusters exhibited distinct laminar distributions, characteristic firing rate patterns, and decision-related dynamics. Such insights were weaker when using feature-based approaches. WaveMAP therefore provides a more nuanced understanding of the dynamics of cell types in cortical circuits.

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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
                06 August 2021
                2021
                : 10
                : e67490
                Affiliations
                [1 ] Psychological and Brain Sciences, Boston University Boston United States
                [2 ] Bernstein Center for Computational Neuroscience, Bernstein Center for Computational Neuroscience Berlin Germany
                [3 ] Department of Anatomy and Neurobiology, Boston University Boston United States
                [4 ] Undergraduate Program in Neuroscience, Boston University Boston United States
                [5 ] Department of Electrical Engineering, Stanford University Stanford United States
                [6 ] Department of Bioengineering, Stanford University Stanford United States
                [7 ] Department of Neurobiology, Stanford University Stanford United States
                [8 ] Wu Tsai Neurosciences Institute, Stanford University Stanford United States
                [9 ] Bio-X Institute, Stanford University Stanford United States
                [10 ] Howard Hughes Medical Institute, Stanford University Stanford United States
                [11 ] Center for Systems Neuroscience, Boston University Boston United States
                [12 ] Department of Biomedical Engineering, Boston University Boston United States
                Wake Forest School of Medicine United States
                Brown University United States
                Wake Forest School of Medicine United States
                Author information
                https://orcid.org/0000-0002-7166-0909
                https://orcid.org/0000-0001-5371-2966
                https://orcid.org/0000-0002-2956-3267
                https://orcid.org/0000-0001-9236-6090
                https://orcid.org/0000-0003-4890-2532
                https://orcid.org/0000-0003-1534-9240
                https://orcid.org/0000-0002-1711-590X
                Article
                67490
                10.7554/eLife.67490
                8452311
                34355695
                dfa659bd-ee50-454c-b96d-e5d86a7a173c
                © 2021, Lee 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
                : 12 February 2021
                : 04 August 2021
                Funding
                Funded by: FundRef http://dx.doi.org/10.13039/100000065, National Institute of Neurological Disorders and Stroke;
                Award ID: R00NS092972
                Award Recipient :
                Funded by: FundRef http://dx.doi.org/10.13039/100000065, National Institute of Neurological Disorders and Stroke;
                Award ID: K99NS092972
                Award Recipient :
                Funded by: FundRef http://dx.doi.org/10.13039/100000011, Howard Hughes Medical Institute;
                Award Recipient :
                Funded by: FundRef http://dx.doi.org/10.13039/100000025, National Institute of Mental Health;
                Award ID: R00MH101234
                Award Recipient :
                Funded by: FundRef http://dx.doi.org/10.13039/100000025, National Institute of Mental Health;
                Award ID: R01MH116008
                Award Recipient :
                Funded by: FundRef http://dx.doi.org/10.13039/100001391, Whitehall Foundation;
                Award ID: 2019-12-77
                Award Recipient :
                Funded by: FundRef http://dx.doi.org/10.13039/100000874, Brain and Behavior Research Foundation;
                Award ID: 27923
                Award Recipient :
                Funded by: FundRef http://dx.doi.org/10.13039/100000052, NIH Office of the Director;
                Award ID: DP1HD075623
                Award Recipient :
                Funded by: FundRef http://dx.doi.org/10.13039/100000055, National Institute on Deafness and Other Communication Disorders;
                Award ID: DC014034
                Award Recipient :
                Funded by: FundRef http://dx.doi.org/10.13039/100000055, National Institute on Deafness and Other Communication Disorders;
                Award ID: DC017844
                Award Recipient :
                Funded by: FundRef http://dx.doi.org/10.13039/100000065, National Institute of Neurological Disorders and Stroke;
                Award ID: NS095548
                Award Recipient :
                Funded by: FundRef http://dx.doi.org/10.13039/100000065, National Institute of Neurological Disorders and Stroke;
                Award ID: NS098968
                Award Recipient :
                Funded by: FundRef http://dx.doi.org/10.13039/100000185, Defense Advanced Research Projects Agency;
                Award ID: N66001-10-C-2010
                Award Recipient :
                Funded by: FundRef http://dx.doi.org/10.13039/100000185, Defense Advanced Research Projects Agency;
                Award ID: W911NF-14-2-0013
                Award Recipient :
                Funded by: FundRef http://dx.doi.org/10.13039/100000893, Simons Foundation;
                Award ID: 325380
                Award Recipient :
                Funded by: FundRef http://dx.doi.org/10.13039/100000893, Simons Foundation;
                Award ID: 543045
                Award Recipient :
                Funded by: FundRef http://dx.doi.org/10.13039/100000065, National Institute of Neurological Disorders and Stroke;
                Award ID: NS122969
                Award Recipient :
                Funded by: FundRef http://dx.doi.org/10.13039/100000006, Office of Naval Research;
                Award ID: N000141812158
                Award Recipient :
                Funded by: FundRef http://dx.doi.org/10.13039/100005492, Stanford University;
                Award Recipient :
                Funded by: Wu Tsai Neurosciences Institute, Stanford University;
                Award Recipient :
                Funded by: FundRef http://dx.doi.org/10.13039/100010865, Stanford Engineering;
                Award Recipient :
                The funders had no role in study design, data collection and interpretation, or the decision to submit the work for publication.
                Categories
                Research Article
                Neuroscience
                Custom metadata
                WaveMAP is a novel approach that combines nonlinear dimensionality reduction with graph clustering on extracellular waveforms to reveal previously obscured cell type diversity in monkey cortex.

                Life sciences
                nonlinear dimensionality reduction,waveforms,cell types,circuits,layers,rhesus macaque
                Life sciences
                nonlinear dimensionality reduction, waveforms, cell types, circuits, layers, rhesus macaque

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