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

Mosher, Clayton P. and Wei, Yina and Kamiński, Jan and Nandi, Anirban and Mamelak, Adam N. and Anastassiou, Costas A. and Rutishauser, Ueli (2020) Cellular Classes in the Human Brain Revealed In Vivo by Heartbeat-Related Modulation of the Extracellular Action Potential Waveform. Cell Reports, 30 (10). pp. 3536-3551. ISSN 2211-1247. PMCID PMC7159630. doi:10.1016/j.celrep.2020.02.027.

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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.

Item Type:Article
Related URLs:
URLURL TypeDescription CentralArticle
Mosher, Clayton P.0000-0002-9213-3059
Nandi, Anirban0000-0002-5794-5553
Mamelak, Adam N.0000-0002-4245-6431
Anastassiou, Costas A.0000-0002-6793-0611
Rutishauser, Ueli0000-0002-9207-7069
Additional Information:© 2020 The Author(s). This is an open access article under the CC BY-NC-ND license ( Received 9 September 2019, Revised 23 December 2019, Accepted 5 February 2020, Available online 10 March 2020. We wish to thank the Allen Institute founder, Paul G. Allen, for his vision, encouragement, and support. We thank all members of the Anastassiou and Rutishauser labs for discussions, Shannon Sullivan, April Carlson, and Nand Chandravadia for their assistance in spike sorting, Anatoly Buchin and Tom Chartrand for their contributions to the optimization and simulation workflow, and Uygar Sümbül for critical comments and discussions. We gratefully acknowledge the willingness of our patients to participate in this study and the staff and physicians of the Epilepsy Monitoring Unit and the Movement Disorders Program at Cedars-Sinai Medical Center for their invaluable assistance. Research reported in this publication was supported by the National Institute of Mental Health, United States (R01MH110831 to U.R.) and the National Institute of Neurological Disorders and Stroke, United States (U01NS103792, U01NS098961 to U.R.). 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. The authors declare no competing interests.
Funding AgencyGrant Number
Subject Keywords:human recordings; heartbeat; cell types; spike waveform; biophysical modeling; slice physiology; morphology; LFP coupling; hippocampus; cardiovascular
Issue or Number:10
PubMed Central ID:PMC7159630
Record Number:CaltechAUTHORS:20200310-101735358
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Official Citation:Clayton P. Mosher, Yina Wei, Jan Kamiński, Anirban Nandi, Adam N. Mamelak, Costas A. Anastassiou, Ueli Rutishauser, Cellular Classes in the Human Brain Revealed In Vivo by Heartbeat-Related Modulation of the Extracellular Action Potential Waveform, Cell Reports, Volume 30, Issue 10, 2020, Pages 3536-3551.e6, ISSN 2211-1247,
Usage Policy:No commercial reproduction, distribution, display or performance rights in this work are provided.
ID Code:101819
Deposited By: Tony Diaz
Deposited On:10 Mar 2020 17:42
Last Modified:15 Feb 2022 23:17

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