Abstract
In vivo calcium imaging through microendoscopic lenses enables imaging of previously inaccessible neuronal populations deep within the brains of freely moving animals. However, it is computationally challenging to extract single-neuronal activity from microendoscopic data, because of the very large background fluctuations and high spatial overlaps intrinsic to this recording modality. Here, we describe a new constrained matrix factorization approach to accurately separate the background and then demix and denoise the neuronal signals of interest. We compared the proposed method against previous independent components analysis and constrained nonnegative matrix factorization approaches. On both simulated and experimental data recorded from mice, our method substantially improved the quality of extracted cellular signals and detected more well-isolated neural signals, especially in noisy data regimes. These advances can in turn significantly enhance the statistical power of downstream analyses, and ultimately improve scientific conclusions derived from microendoscopic data.
Article and author information
Author details
Funding
National Institute of Mental Health
- Pengcheng Zhou
- Jessica C Jimenez
- Rene Hen
- Mazen A Kheirbek
- Robert E Kass
New York State Stem Cell Science
- Jessica C Jimenez
- Rene Hen
Hope for Depression Research Foundation
- Jessica C Jimenez
- Rene Hen
Canadian Institutes of Health Research
- Shay Q Neufeld
Simons Foundation
- Andrea Giovannucci
- Johannes Friedrich
- Eftychios A Pnevmatikakis
- Garret D Stuber
- Liam Paninski
International Mental Health Research Organization
- Mazen A Kheirbek
National Institute of Neurological Disorders and Stroke
- Bernardo L Sabatini
National Institute on Drug Abuse
- Pengcheng Zhou
- Jose Rodriguez-Romaguera
- Garret D Stuber
Intelligence Advanced Research Projects Activity
- Pengcheng Zhou
- Liam Paninski
Defense Advanced Research Projects Agency
- Liam Paninski
Army Research Office
- Liam Paninski
National Institute of Biomedical Imaging and Bioengineering
- Liam Paninski
Eunice Kennedy Shriver National Institute of Child Health and Human Development
- Shanna L Resendez
- Garret D Stuber
Howard Hughes Medical Institute
- Jessica C Jimenez
National Institute on Aging
- Jessica C Jimenez
- Rene Hen
The funders had no role in study design, data collection and interpretation, or the decision to submit the work for publication.
Ethics
Animal experimentation: These procedures were conducted in accordance with the Guide for the Care and Use of Laboratory Animals, as adopted by the NIH, and with approval from the Harvard Standing Committee on Animal Care (protocol number: IS00000571 ), or the University of North Carolina Institutional Animal Care and Use Committee (UNC IACUC, protocol number: 16-075.0), or the New York State Psychiatric Institutional Animal Care and Use Committee (protocol number: NYSPI-1412 ).
Reviewing Editor
- David C Van Essen, Washington University in St. Louis, United States
Publication history
- Received: May 19, 2017
- Accepted: February 20, 2018
- Accepted Manuscript published: February 22, 2018 (version 1)
- Version of Record published: March 27, 2018 (version 2)
Copyright
© 2018, Zhou et al.
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.
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