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

Abstract
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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 featurebased approaches. WaveMAP therefore provides a more nuanced understanding of the dynamics of cell types in cortical circuits.

Data availability

Data generated or analysed during this study are included in the linked Dryad repository (doi:10.5061/dryad.z612jm6cf). Source data for all figures are also in this zip file.

The following data sets were generated

(2021) WaveMAP analysis of extracellular waveforms from monkey premotor cortex during decision-making
https://creativecommons.org/publicdomain/zero/1.0/.

http://dx.doi.org/10.5061/dryad.z612jm6cf

Article and author information

Author details

Eric Kenji Lee

Psychological and Brain Sciences, BOSTON UNIVERSITY, BOSTON, United States

Competing interests
The authors declare that no competing interests exist.

"This ORCID iD identifies the author of this article:" 0000-0002-7166-0909
Hymavathy Balasubramanian

Bernstein Center for Computational Neuroscience, Bernstein Center for Computational Neuroscience, Berlin, Germany

Competing interests
The authors declare that no competing interests exist.
Alexandra Tsolias

Anatomy and Neurobiology, Boston University, Boston, United States

Competing interests
The authors declare that no competing interests exist.
Stephanie Udochku Anakwe

Undergraduate Program in Neuroscience, Boston University, Boston, United States

Competing interests
The authors declare that no competing interests exist.
Maria Medalla

Anatomy & Neurobiology, Boston University, Boston, United States

Competing interests
The authors declare that no competing interests exist.
Krishna V Shenoy

Department of Electrical Engineering, Stanford University, Stanford, United States

Competing interests
The authors declare that no competing interests exist.
Chandramouli Chandrasekaran

Anatomy and Neurobiology, Boston University, Boston, United States

For correspondence
cchandr1@bu.edu

Competing interests
The authors declare that no competing interests exist.

"This ORCID iD identifies the author of this article:" 0000-0002-1711-590X

Funding

National Institute of Neurological Disorders and Stroke (R00NS092972)

Chandramouli Chandrasekaran

National Institute on Deafness and Other Communication Disorders (DC017844)

Krishna V Shenoy

National Institute of Neurological Disorders and Stroke (NS095548)

Krishna V Shenoy

National Institute of Neurological Disorders and Stroke (NS098968)

Krishna V Shenoy

Defense Advanced Research Projects Agency (N66001-10-C-2010)

Krishna V Shenoy

Defense Advanced Research Projects Agency (W911NF-14-2-0013)

Krishna V Shenoy

Simons Foundation (325380)

Krishna V Shenoy

Simons Foundation (543045)

Krishna V Shenoy

National Institute of Neurological Disorders and Stroke (122969)

Chandramouli Chandrasekaran

Office of Naval Research (N000141812158)

Krishna V Shenoy

Larry and Pamela Garlick

Krishna V Shenoy

National Institute of Neurological Disorders and Stroke (K99NS092972)

Chandramouli Chandrasekaran

Wu Tsai Neurosciences Institute, Stanford University

Krishna V Shenoy

Hong Seh and Vivian H Lim Endowed Professorship

Krishna V Shenoy

Howard Hughes Medical Institute

Krishna V Shenoy

National Institute of Mental Health (R00MH101234)

Maria Medalla

National Institute of Mental Health (R01MH116008)

Maria Medalla

Whitehall Foundation (2019-12-77)

Chandramouli Chandrasekaran

Brain and Behavior Research Foundation (27923)

Chandramouli Chandrasekaran

NIH Office of the Director (DP1HD075623)

Krishna V Shenoy

National Institute on Deafness and Other Communication Disorders (DC014034)

Krishna V Shenoy

The funders had no role in study design, data collection and interpretation, or the decision to submit the work for publication.

Ethics

Animal experimentation: This study was performed in strict accordance with the recommendations in the Guide for the Care and Use of Laboratory Animals of the National Institutes of Health. All of the procedures were approved were approved by the Stanford Administrative Panel on Laboratory Animal Care (APLAC, Protocol Number 8856, entitled "Cortical Processing of Arm Movements"). Surgical procedures were performed under anesthesia, and every effort was made to minimize suffering. Appropriate analgesia, pain relief, and antibiotics were administered to the animals when needed after surgical approval.

Copyright

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