Mapping of Brain Activity by Automated Volume Analysis of Immediate Early Genes
Open accessAbstract
Understanding how neural information is processed in physiological and pathological states would benefit from precise detection, localization, and quantification of the activity of all neurons across the entire brain, which has not, to date, been achieved in the mammalian brain. We introduce a pipeline for high-speed acquisition of brain activity at cellular resolution through profiling immediate early gene expression using immunostaining and light-sheet fluorescence imaging, followed by automated mapping and analysis of activity by an open-source software program we term ClearMap. We validate the pipeline first by analysis of brain regions activated in response to haloperidol. Next, we report new cortical regions downstream of whisker-evoked sensory processing during active exploration. Last, we combine activity mapping with axon tracing to uncover new brain regions differentially activated during parenting behavior. This pipeline is widely applicable to different experimental paradigms, including animal species for which transgenic activity reporters are not readily available.
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Several approaches for image analysis of LSFM datasets have been introduced in recent years, but these methods are typically limited to selected organs and do not provide integrated whole-body quantification of elongated structures.
“Although several approaches for image analysis of light-sheet fluorescence microscopy (LSFM) datasets have been introduced in recent years6–10, these methods are typically limited to selected organs and do not provide integrated whole-body quantification of elongated structures.”
From A deep-learning framework reveals whole-body perturbations at cell level (2026) · cites this paper as [8]
Tools for comprehensive, high-resolution analysis of disease-associated changes at the whole-body scale have been lacking.
“However, tools for comprehensive, high-resolution analysis of disease-associated changes at the whole-body scale have been lacking.”
From A deep-learning framework reveals whole-body perturbations at cell level (2026) · cites this paper as [8]
Methods that identify active cells through immediate early gene expression lack the temporal resolution needed to capture alertness fluctuations on the order of seconds, precluding such a screen in mammals.
“However, methods that identify active cells through immediate early gene expression do not have the temporal resolution needed to capture alertness fluctuations on the order of seconds (Guenthner et al., 2013; Renier et al., 2016; Ye et al., 2016), precluding such a screen in mammals.”
From Ancestral Circuits for the Coordinated Modulation of Brain State (2017) · cites this paper as Renier et al., 2016
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- Authors
- Renier, N., Adams, E. L., Kirst, C., Wu, Z., Azevedo, R., Kohl, J., Autry, A. E., Kadiri, L., Umadevi Venkataraju, K., Zhou, Y., Wang, V. X., Tang, C. Y., Olsen, O., Dulac, C., Osten, P., & Tessier-Lavigne, M.
- Affiliations
- Rockefeller University (US)
- Howard Hughes Medical Institute (US)
- Certerra (United States) (US)
- Icahn School of Medicine at Mount Sinai (US)
- Cold Spring Harbor Laboratory (US)
- ORCID
- Venue
- Cell
- Publisher
- Elsevier BV
- Published
- 2016-06
- Volume
- 165
- Issue
- 7
- Pages
- 1789-1802
- ISSN
- 0092-8674 (ISSN-L)
- PMC
- PMC4912438
- OpenAlex
- W2408110716
- Cited by
- 918
- References
- 40
- Citations by year
- 2026: 80 · 2025: 115 · 2024: 114 · 2023: 99 · 2022: 94 · 2021: 120 · 2020: 107 · 2019: 83 · 2018: 58 · 2017: 36 · 2016: 10
- FWCI
- 39.15
- Type
- journal article
- Language
- en
- Open access
- bronze
- doi.org
- Licence
- Locations
- Cell (publishedVersion)
- PubMed (publishedVersion)
- Europe PMC (PubMed Central) (acceptedVersion)
- PubMed Central (acceptedVersion)
- Cold Spring Harbor Laboratory Institutional Repository (Cold Spring Harbor Laboratory) (acceptedVersion)
- Digital Access to Scholarship at Harvard (DASH) (Harvard University) (submittedVersion, cc-by)
- Funders
- Eunice Kennedy Shriver National Institute of Child Health and Human Development (F32HD078040, 1R01HD082131-01A1)
- National Institutes of Health (F32HD078040, 1R01HD082131-01A1)
- Howard Hughes Medical Institute (F32HD078040, 1R01HD082131-01A1)
- Rockefeller University (F32HD078040, 1R01HD082131-01A1)
- National Alliance for Research on Schizophrenia and Depression (F32HD078040, 1R01HD082131-01A1)
- EMBO (F32HD078040, 1R01HD082131-01A1)
- Topics
- Life Sciences › Biochemistry, Genetics and Molecular Biology › Biophysics › Cell Image Analysis Techniques
- Life Sciences › Biochemistry, Genetics and Molecular Biology › Biophysics › Advanced Fluorescence Microscopy Techniques
- Life Sciences › Neuroscience › Cellular and Molecular Neuroscience › Neuroscience and Neuropharmacology Research
- Keywords
- brain activity mapping, immediate early gene expression, neuronal activity imaging, immunostaining, haloperidol, cortical activation, axon tracing, parental behavior, cellular resolution imaging
- MeSH terms
- Animals, Behavior, Animal, Brain, Exploratory Behavior, Haloperidol, Immunohistochemistry, Mice, Inbred C57BL, Antipsychotic Agents, Genes, Immediate-Early, Mice, Neuroimaging
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