Efficient and accurate extraction of in vivo calcium signals from microendoscopic video data
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.
Data availability
-
Data from: Efficient and accurate extraction of in vivo calcium signals from microendoscopic video dataAvailable at Dryad Digital Repository under a CC0 Public Domain Dedication.
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.
Metrics
-
- 22,258
- Page views
-
- 3,163
- Downloads
-
- 175
- Citations
Article citation count generated by polling the highest count across the following sources: Crossref, Scopus, PubMed Central.
Download links
Downloads (link to download the article as PDF)
Open citations (links to open the citations from this article in various online reference manager services)
Cite this article (links to download the citations from this article in formats compatible with various reference manager tools)
Further reading
-
- Neuroscience
Cochlear implants are neuroprosthetic devices that can restore hearing in people with severe to profound hearing loss by electrically stimulating the auditory nerve. Because of physical limitations on the precision of this stimulation, the acoustic information delivered by a cochlear implant does not convey the same level of acoustic detail as that conveyed by normal hearing. As a result, speech understanding in listeners with cochlear implants is typically poorer and more effortful than in listeners with normal hearing. The brain networks supporting speech understanding in listeners with cochlear implants are not well understood, partly due to difficulties obtaining functional neuroimaging data in this population. In the current study, we assessed the brain regions supporting spoken word understanding in adult listeners with right unilateral cochlear implants (n=20) and matched controls (n=18) using high-density diffuse optical tomography (HD-DOT), a quiet and non-invasive imaging modality with spatial resolution comparable to that of functional MRI. We found that while listening to spoken words in quiet, listeners with cochlear implants showed greater activity in the left prefrontal cortex than listeners with normal hearing, specifically in a region engaged in a separate spatial working memory task. These results suggest that listeners with cochlear implants require greater cognitive processing during speech understanding than listeners with normal hearing, supported by compensatory recruitment of the left prefrontal cortex.
-
- Neuroscience
Sleep strongly affects synaptic strength, making it critical for cognition, especially learning and memory formation. Whether and how sleep deprivation modulates human brain physiology and cognition is not well understood. Here we examined how overnight sleep deprivation vs overnight sufficient sleep affects (a) cortical excitability, measured by transcranial magnetic stimulation, (b) inducibility of long-term potentiation (LTP)- and long-term depression (LTD)-like plasticity via transcranial direct current stimulation (tDCS), and (c) learning, memory, and attention. The results suggest that sleep deprivation upscales cortical excitability due to enhanced glutamate-related cortical facilitation and decreases and/or reverses GABAergic cortical inhibition. Furthermore, tDCS-induced LTP-like plasticity (anodal) abolishes while the inhibitory LTD-like plasticity (cathodal) converts to excitatory LTP-like plasticity under sleep deprivation. This is associated with increased EEG theta oscillations due to sleep pressure. Finally, we show that learning and memory formation, behavioral counterparts of plasticity, and working memory and attention, which rely on cortical excitability, are impaired during sleep deprivation. Our data indicate that upscaled brain excitability and altered plasticity, due to sleep deprivation, are associated with impaired cognitive performance. Besides showing how brain physiology and cognition undergo changes (from neurophysiology to higher-order cognition) under sleep pressure, the findings have implications for variability and optimal application of noninvasive brain stimulation.