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

Author:

Lee Eric Kenji1ORCID,Balasubramanian Hymavathy2ORCID,Tsolias Alexandra3ORCID,Anakwe Stephanie Udochukwu4ORCID,Medalla Maria3ORCID,Shenoy Krishna V56789ORCID,Chandrasekaran Chandramouli131011ORCID

Affiliation:

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. Center for Systems Neuroscience, Boston University, Boston, United States

11. Department of Biomedical Engineering, Boston University, Boston, United States

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.

Funder

National Institute of Neurological Disorders and Stroke

Howard Hughes Medical Institute

National Institute of Mental Health

Whitehall Foundation

Brain and Behavior Research Foundation

NIH Office of the Director

National Institute on Deafness and Other Communication Disorders

Defense Advanced Research Projects Agency

Simons Foundation

Office of Naval Research

Stanford University

Wu Tsai Neurosciences Institute, Stanford University

Stanford Engineering

Publisher

eLife Sciences Publications, Ltd

Subject

General Immunology and Microbiology,General Biochemistry, Genetics and Molecular Biology,General Medicine,General Neuroscience

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