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      Cellular Classes in the Human Brain Revealed In Vivo by Heartbeat-Related Modulation of the Extracellular Action Potential Waveform

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          SUMMARY

          Determining cell types is critical for understanding neural circuits but remains elusive in the living human brain. Current approaches discriminate units into putative cell classes using features of the extracellular action potential (EAP); in absence of ground truth data, this remains a problematic procedure. We find that EAPs in deep structures of the brain exhibit robust and systematic variability during the cardiac cycle. These cardiac-related features refine neural classification. We use these features to link bio-realistic models generated from in vitro human whole-cell recordings of morphologically classified neurons to in vivo recordings. We differentiate aspiny inhibitory and spiny excitatory human hippocampal neurons and, in a second stage, demonstrate that cardiac-motion features reveal two types of spiny neurons with distinct intrinsic electrophysiological properties and phase-locking characteristics to endogenous oscillations. This multi-modal approach markedly improves cell classification in humans, offers interpretable cell classes, and is applicable to other brain areas and species.

          In Brief

          During the heartbeat, the brain pulsates and recording electrodes move. Mosher et al. show that, in the living human brain, such movement affects the spike waveform leading to enhanced separation between cell types. Single-cell models of human neurons reveal distinct properties of the cell types identified in vivo.

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          Author and article information

          Journal
          101573691
          39703
          Cell Rep
          Cell Rep
          Cell reports
          2211-1247
          20 March 2020
          10 March 2020
          15 April 2020
          : 30
          : 10
          : 3536-3551.e6
          Affiliations
          [1 ]Department of Neurosurgery, Cedars-Sinai Medical Center, Los Angeles, CA 90048, USA
          [2 ]Allen Institute for Brain Science, Seattle, WA 98109, USA
          [3 ]Division of Neurology, University of British Columbia, Vancouver, BC V6T 1Z4, Canada
          [4 ]Center for Neural Science and Medicine, Cedars-Sinai Medical Center, Los Angeles, CA 90048, USA
          [5 ]Department of Neurology, Cedars-Sinai Medical Center, Los Angeles, CA 90048, USA
          [6 ]Division of Biology and Biological Engineering, Caltech, Pasadena, CA 91125, USA
          [7 ]These authors contributed equally
          [8 ]These authors contributed equally
          [9 ]Lead Contact
          Author notes

          AUTHOR CONTRIBUTIONS

          C.P.M., J.K., A.N.M., and U.R. designed in vivo experiments and collected in vivo extracellular data. A.N., Y.W., and C.A.A. constructed the all-active human single-neuron models and simulated data. A.N.M. performed surgery and provided patient care. C.P.M. and Y.W. performed data analysis with guidance from C.A.A. and U.R. J.K. first noticed the cardiac-related changes in the electrophysiology. C.P.M. wrote the initial draft of the manuscript. All authors discussed the results at all stages of the project and contributed to the final manuscript.

          Article
          PMC7159630 PMC7159630 7159630 nihpa1574780
          10.1016/j.celrep.2020.02.027
          7159630
          32160555
          dcb015eb-7680-4374-abcf-d0ad529597e0
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