Efficient and accurate extraction of in vivo calcium signals from microendoscopic video data
- Carnegie Mellon University, United States
- University of North Carolina at Chapel Hill, United States
- Columbia University, United States
- Harvard Medical School, United States
- Flatiron Institute, Simons Foundation, United States
- University of California, San Francisco, United States
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
Johannes Friedrich
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.
Reviewing Editor
- David C Van Essen, Washington University in St. Louis, United States
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 ).
Version 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
-
- 27,866
- views
-
- 3,818
- downloads
-
- 314
- citations
Views, downloads and citations are aggregated across all versions of this paper published by eLife.
Download links
A two-part list of links to download the article, or parts of the article, in various formats.
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)
Efficient and accurate extraction of in vivo calcium signals from microendoscopic video data
eLife 7:e28728.
https://doi.org/10.7554/eLife.28728
Further reading
-
- Genetics and Genomics
- Neuroscience
Genome-wide association studies have revealed >270 loci associated with schizophrenia risk, yet these genetic factors do not seem to be sufficient to fully explain the molecular determinants behind this psychiatric condition. Epigenetic marks such as post-translational histone modifications remain largely plastic during development and adulthood, allowing a dynamic impact of environmental factors, including antipsychotic medications, on access to genes and regulatory elements. However, few studies so far have profiled cell-specific genome-wide histone modifications in postmortem brain samples from schizophrenia subjects, or the effect of antipsychotic treatment on such epigenetic marks. Here, we conducted ChIP-seq analyses focusing on histone marks indicative of active enhancers (H3K27ac) and active promoters (H3K4me3), alongside RNA-seq, using frontal cortex samples from antipsychotic-free (AF) and antipsychotic-treated (AT) individuals with schizophrenia, as well as individually matched controls (n=58). Schizophrenia subjects exhibited thousands of neuronal and non-neuronal epigenetic differences at regions that included several susceptibility genetic loci, such as NRG1, DISC1, and DRD3. By analyzing the AF and AT cohorts separately, we identified schizophrenia-associated alterations in specific transcription factors, their regulatees, and epigenomic and transcriptomic features that were reversed by antipsychotic treatment; as well as those that represented a consequence of antipsychotic medication rather than a hallmark of schizophrenia in postmortem human brain samples. Notably, we also found that the effect of age on epigenomic landscapes was more pronounced in frontal cortex of AT-schizophrenics, as compared to AF-schizophrenics and controls. Together, these data provide important evidence of epigenetic alterations in the frontal cortex of individuals with schizophrenia, and remark for the first time on the impact of age and antipsychotic treatment on chromatin organization.
-
- Neuroscience
Mechanosensory neurons located across the body surface respond to tactile stimuli and elicit diverse behavioral responses, from relatively simple stimulus location-aimed movements to complex movement sequences. How mechanosensory neurons and their postsynaptic circuits influence such diverse behaviors remains unclear. We previously discovered that Drosophila perform a body location-prioritized grooming sequence when mechanosensory neurons at different locations on the head and body are simultaneously stimulated by dust (Hampel et al., 2017; Seeds et al., 2014). Here, we identify nearly all mechanosensory neurons on the Drosophila head that individually elicit aimed grooming of specific head locations, while collectively eliciting a whole head grooming sequence. Different tracing methods were used to reconstruct the projections of these neurons from different locations on the head to their distinct arborizations in the brain. This provides the first synaptic resolution somatotopic map of a head, and defines the parallel-projecting mechanosensory pathways that elicit head grooming.
