Fluorescent transgenic mouse models for whole-brain imaging in health and disease
A paradigm shift is occurring in neuroscience and in general in life sciences converting biomedical research from a descriptive discipline into a quantitative, predictive, actionable science. Living systems are becoming amenable to quantitative description, with profound consequences for our ability...
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| Format: | Article |
| Language: | English |
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Frontiers Media S.A.
2022-09-01
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| Series: | Frontiers in Molecular Neuroscience |
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| Online Access: | https://www.frontiersin.org/articles/10.3389/fnmol.2022.958222/full |
| _version_ | 1798001595327184896 |
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| author | Adrian Arias Linus Manubens-Gil Mara Dierssen Mara Dierssen Mara Dierssen |
| author_facet | Adrian Arias Linus Manubens-Gil Mara Dierssen Mara Dierssen Mara Dierssen |
| author_sort | Adrian Arias |
| collection | DOAJ |
| description | A paradigm shift is occurring in neuroscience and in general in life sciences converting biomedical research from a descriptive discipline into a quantitative, predictive, actionable science. Living systems are becoming amenable to quantitative description, with profound consequences for our ability to predict biological phenomena. New experimental tools such as tissue clearing, whole-brain imaging, and genetic engineering technologies have opened the opportunity to embrace this new paradigm, allowing to extract anatomical features such as cell number, their full morphology, and even their structural connectivity. These tools will also allow the exploration of new features such as their geometrical arrangement, within and across brain regions. This would be especially important to better characterize brain function and pathological alterations in neurological, neurodevelopmental, and neurodegenerative disorders. New animal models for mapping fluorescent protein-expressing neurons and axon pathways in adult mice are key to this aim. As a result of both developments, relevant cell populations with endogenous fluorescence signals can be comprehensively and quantitatively mapped to whole-brain images acquired at submicron resolution. However, they present intrinsic limitations: weak fluorescent signals, unequal signal strength across the same cell type, lack of specificity of fluorescent labels, overlapping signals in cell types with dense labeling, or undetectable signal at distal parts of the neurons, among others. In this review, we discuss the recent advances in the development of fluorescent transgenic mouse models that overcome to some extent the technical and conceptual limitations and tradeoffs between different strategies. We also discuss the potential use of these strains for understanding disease. |
| first_indexed | 2024-04-11T11:38:46Z |
| format | Article |
| id | doaj.art-44889b43767d415584901255bde4393d |
| institution | Directory Open Access Journal |
| issn | 1662-5099 |
| language | English |
| last_indexed | 2024-04-11T11:38:46Z |
| publishDate | 2022-09-01 |
| publisher | Frontiers Media S.A. |
| record_format | Article |
| series | Frontiers in Molecular Neuroscience |
| spelling | doaj.art-44889b43767d415584901255bde4393d2022-12-22T04:25:53ZengFrontiers Media S.A.Frontiers in Molecular Neuroscience1662-50992022-09-011510.3389/fnmol.2022.958222958222Fluorescent transgenic mouse models for whole-brain imaging in health and diseaseAdrian Arias0Linus Manubens-Gil1Mara Dierssen2Mara Dierssen3Mara Dierssen4Department of System Biology, Centre for Genomic Regulation, The Barcelona Institute of Science and Technology, Barcelona, SpainInstitute for Brain and Intelligence, Southeast University, Nanjing, ChinaDepartment of System Biology, Centre for Genomic Regulation, The Barcelona Institute of Science and Technology, Barcelona, SpainDepartment of Experimental and Health Sciences, University Pompeu Fabra, Barcelona, SpainCentro de Investigación Biomédica en Red de Enfermedades Raras (CIBERER), Barcelona, SpainA paradigm shift is occurring in neuroscience and in general in life sciences converting biomedical research from a descriptive discipline into a quantitative, predictive, actionable science. Living systems are becoming amenable to quantitative description, with profound consequences for our ability to predict biological phenomena. New experimental tools such as tissue clearing, whole-brain imaging, and genetic engineering technologies have opened the opportunity to embrace this new paradigm, allowing to extract anatomical features such as cell number, their full morphology, and even their structural connectivity. These tools will also allow the exploration of new features such as their geometrical arrangement, within and across brain regions. This would be especially important to better characterize brain function and pathological alterations in neurological, neurodevelopmental, and neurodegenerative disorders. New animal models for mapping fluorescent protein-expressing neurons and axon pathways in adult mice are key to this aim. As a result of both developments, relevant cell populations with endogenous fluorescence signals can be comprehensively and quantitatively mapped to whole-brain images acquired at submicron resolution. However, they present intrinsic limitations: weak fluorescent signals, unequal signal strength across the same cell type, lack of specificity of fluorescent labels, overlapping signals in cell types with dense labeling, or undetectable signal at distal parts of the neurons, among others. In this review, we discuss the recent advances in the development of fluorescent transgenic mouse models that overcome to some extent the technical and conceptual limitations and tradeoffs between different strategies. We also discuss the potential use of these strains for understanding disease.https://www.frontiersin.org/articles/10.3389/fnmol.2022.958222/fullfluorescent transgenic modelswhole-brain imagingcell detection and countingmorphological reconstructioncomputational neuroscience |
| spellingShingle | Adrian Arias Linus Manubens-Gil Mara Dierssen Mara Dierssen Mara Dierssen Fluorescent transgenic mouse models for whole-brain imaging in health and disease Frontiers in Molecular Neuroscience fluorescent transgenic models whole-brain imaging cell detection and counting morphological reconstruction computational neuroscience |
| title | Fluorescent transgenic mouse models for whole-brain imaging in health and disease |
| title_full | Fluorescent transgenic mouse models for whole-brain imaging in health and disease |
| title_fullStr | Fluorescent transgenic mouse models for whole-brain imaging in health and disease |
| title_full_unstemmed | Fluorescent transgenic mouse models for whole-brain imaging in health and disease |
| title_short | Fluorescent transgenic mouse models for whole-brain imaging in health and disease |
| title_sort | fluorescent transgenic mouse models for whole brain imaging in health and disease |
| topic | fluorescent transgenic models whole-brain imaging cell detection and counting morphological reconstruction computational neuroscience |
| url | https://www.frontiersin.org/articles/10.3389/fnmol.2022.958222/full |
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