Year: 2022
Type: review
Abstract: 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.
Authors: Adrian Arias, Linus Manubens-Gil, Mara Dierssen
Language: English
Subfield: Biophysics
Domain: Life Sciences
Open Access status: gold
Estimated APC paid: $2,950
Funders: Fundació la Marató de TV3, EU Joint Programme – Neurodegenerative Disease Research, European Commission, Fondation Jérôme Lejeune, Generalitat de Catalunya, Departament d'Innovació, Universitats i Empresa, Generalitat de Catalunya, Ministerio de Ciencia e Innovación, National Institutes of Health, Horizon 2020 Framework Programme, Departament d'Universitats, Recerca i Societat de la Informació, Agencia Estatal de Investigación, National Institute of Biomedical Imaging and Bioengineering
Awards: G1106039936, G1175115578, G1601966056, G1855990336, G2064873908, G2083143732, G2262748287, G2309174360, G2601397997, G2660406951, G3005324705, G300979063, G3067837860, G3196131747, G3288897321, G3480869486, G3518538256, G3546882995, G3681454997, G3690828678, G3891055409, G4042783231, New methods and theories to interrogate organizational principles from single cell to neuronal networks, G425668148, G430777504, Gene overdosage and comorbidities during the early lifetime in Down Syndrome, G5080475149, G5195188938, G5421974903, G589576360, G6366842693, G7084143925, G7425137858, G7520681623, G7773939433, G8130184278, G847219688, G8684520763, G99296377
OpenAlex ID: W4297009460