Large-scale, cell-resolution volumetric mapping allows layer-specific investigation of human brain cytoarchitecture

Year: 2021

Authors: Costantini I., Mazzamuto G., Roffilli M., Laurino A., Castelli FM., Neri M., Lughi G., Simonetto A., Lazzeri E., Pesce L., Destrieux C., Silvestri L., Conti V., Guerrini R., Pavone FS

Autors Affiliation: European Laboratory for Non-Linear Spectroscopy (LENS), University of Florence, Sesto Fiorentino, Italy Department of Biology, University of Florence, Italy National Institute of Optics (INO), National Research Council (CNR), Sesto Fiorentino, Italy Bioretics srl, Cesena, Italy Department of Physics, University of Florence, Italy UMR 1253, iBrain, Université de Tours, Inserm, Tours, France Pediatric Neurology, Neurogenetics and Neurobiology Unit and Laboratories, A. Meyer Children’s Hospital, University of Florence, Florence, Italy

Abstract: Although neuronal density analysis on human brain slices is available from stereological studies, data on the spatial distribution of neurons in 3D are still missing. Since the neuronal organization is very inhomogeneous in the cerebral cortex, it is critical to map all neurons in a given volume rather than relying on sparse sampling methods. To achieve this goal, we implement a new tissue transformation protocol to clear and label human brain tissues and we exploit the high-resolution optical sectioning of two-photon fluorescence microscopy to perform 3D mesoscopic reconstruction. We perform neuronal mapping of 100mm human brain samples and evaluate the volume and density distribution of neurons from various areas of the cortex originating from different subjects (young, adult, and elderly, both healthy and pathological). The quantitative evaluation of the density in combination with the mean volume of the thousands of neurons identified within the specimens, allow us to determine the layer-specific organization of the cerebral architecture.


Volume: 12      Pages from: 3684  to: 3699

More Information: Funding. Ministero della Salute (RF201302355240) ; Horizon 2020 Framework Programme (785907, 945539) ; National Institute of Mental Health (1U01MH11702301) ; Ministero dell´Istruzione, dell´Universita e della Ricerca (Eurobioimaging Italian Nodes) ; Fondazione Cassa di Risparmio di Firenze.
KeyWords: human brain, cytoarchitecture, cell segmentation, cell counting
DOI: 10.1364/BOE.415555

Citations: 15
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