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Wide-field optical mapping of neural activity and brain haemodynamics: considerations and novel approaches
Open accessAbstract
Although modern techniques such as two-photon microscopy can now provide cellular-level three-dimensional imaging of the intact living brain, the speed and fields of view of these techniques remain limited. Conversely, two-dimensional wide-field optical mapping (WFOM), a simpler technique that uses a camera to observe large areas of the exposed cortex under visible light, can detect changes in both neural activity and haemodynamics at very high speeds. Although WFOM may not provide single-neuron or capillary-level resolution, it is an attractive and accessible approach to imaging large areas of the brain in awake, behaving mammals at speeds fast enough to observe widespread neural firing events, as well as their dynamic coupling to haemodynamics. Although such wide-field optical imaging techniques have a long history, the advent of genetically encoded fluorophores that can report neural activity with high sensitivity, as well as modern technologies such as light emitting diodes and sensitive and high-speed digital cameras have driven renewed interest in WFOM. To facilitate the wider adoption and standardization of WFOM approaches for neuroscience and neurovascular coupling research, we provide here an overview of the basic principles of WFOM, considerations for implementation of wide-field fluorescence imaging of neural activity, spectroscopic analysis and interpretation of results. This article is part of the themed issue ‘Interpreting BOLD: a dialogue between cognitive and cellular neuroscience’.
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“Violet to yellow excitation and emission light are well absorbed by the blood within the vasculature. Therefore, when fluorescent proteins are diffusely expressed in brain cells, blood vessels that lack these proteins appear as dark shadows36,37.”
From Energy paradox in REM sleep: balancing supply and consumption in brain metabolism (2026) · cites this paper as [37]
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“Vessel dilation consequently reduces the detectable parenchymal fluorescence.”
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Metadata
- Authors
- Ma, Y., Shaik, M. A., Kim, S. H., Kozberg, M. G., Thibodeaux, D. N., Zhao, H. T., Yu, H., & Hillman, E. M. C.
- Affiliations
- Mortimer B. Zuckerman Mind Brain Behavior Institute (US)
- Corresponding author
- Hillman, Elizabeth M. C.
- ORCID
- Venue
- Philosophical Transactions of the Royal Society B: Biological Sciences
- Publisher
- The Royal Society
- Published
- 2016-10-05
- Volume
- 371
- Issue
- 1705
- Pages
- 20150360
- ISSN
- 0962-8436 (ISSN-L)
- 1471-2970
- PMC
- PMC5003860
- OpenAlex
- W2513047215
- Cited by
- 335
- References
- 85
- Citations by year
- 2026: 24 · 2025: 54 · 2024: 52 · 2023: 47 · 2022: 40 · 2021: 31 · 2020: 24 · 2019: 21 · 2018: 24 · 2017: 15 · 2016: 3
- FWCI
- 3.25
- Type
- journal article
- Language
- en
- Update notices
- correction (2017-02-19)
- Open access
- hybrid
- doi.org
- Locations
- Philosophical Transactions of the Royal Society B Biological Sciences (publishedVersion, cc-by)
- PubMed Central (publishedVersion, cc-by)
- PubMed (publishedVersion)
- Funders
- National Science Foundation (0954796)
- U.S. Department of Defense (MURI W911NF-12-1-0594)
- National Institute of Neurological Disorders and Stroke (1R01NS063226, 5U01NS094296, 1R21NS053684, 1R01NS076628)
- National Eye Institute (1R01EY019500)
- Topics
- Health Sciences › Medicine › Radiology, Nuclear Medicine and Imaging › Optical Imaging and Spectroscopy Techniques
- Life Sciences › Biochemistry, Genetics and Molecular Biology › Biophysics › Advanced Fluorescence Microscopy Techniques
- Life Sciences › Neuroscience › Cognitive Neuroscience › Neural dynamics and brain function
- Keywords
- neuronal activity imaging, neurovascular coupling, genetically encoded fluorescent indicators, wide-field fluorescence imaging, spectroscopic analysis, cortical imaging, BOLD signal
- MeSH terms
- Animals, Brain, Brain Mapping, Hemodynamics, Humans, Neurons, Mice, Rats, Optical Imaging
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