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Proceedings Paper

Mapping whole-brain activity with cellular resolution by light-sheet microscopy and high-throughput image analysis (Conference Presentation)
Author(s): Ludovico Silvestri; Nikita Rudinskiy; Marco Paciscopi; Marie Caroline Müllenbroich; Irene Costantini; Leonardo Sacconi; Paolo Frasconi; Bradley T. Hyman; Francesco S. Pavone
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Paper Abstract

Mapping neuronal activity patterns across the whole brain with cellular resolution is a challenging task for state-of-the-art imaging methods. Indeed, despite a number of technological efforts, quantitative cellular-resolution activation maps of the whole brain have not yet been obtained. Many techniques are limited by coarse resolution or by a narrow field of view. High-throughput imaging methods, such as light sheet microscopy, can be used to image large specimens with high resolution and in reasonable times. However, the bottleneck is then moved from image acquisition to image analysis, since many TeraBytes of data have to be processed to extract meaningful information. Here, we present a full experimental pipeline to quantify neuronal activity in the entire mouse brain with cellular resolution, based on a combination of genetics, optics and computer science. We used a transgenic mouse strain (Arc-dVenus mouse) in which neurons which have been active in the last hours before brain fixation are fluorescently labelled. Samples were cleared with CLARITY and imaged with a custom-made confocal light sheet microscope. To perform an automatic localization of fluorescent cells on the large images produced, we used a novel computational approach called semantic deconvolution. The combined approach presented here allows quantifying the amount of Arc-expressing neurons throughout the whole mouse brain. When applied to cohorts of mice subject to different stimuli and/or environmental conditions, this method helps finding correlations in activity between different neuronal populations, opening the possibility to infer a sort of brain-wide 'functional connectivity' with cellular resolution.

Paper Details

Date Published: 26 April 2016
PDF: 1 pages
Proc. SPIE 9690, Clinical and Translational Neurophotonics; Neural Imaging and Sensing; and Optogenetics and Optical Manipulation, 969012 (26 April 2016); doi: 10.1117/12.2208603
Show Author Affiliations
Ludovico Silvestri, European Lab. for Non-linear Spectroscopy (Italy)
Nikita Rudinskiy, Massachusetts General Hospital (United States)
Marco Paciscopi, Univ. degli Studi di Firenze (Italy)
Marie Caroline Müllenbroich, European Lab. for Non-linear Spectroscopy (Italy)
Univ. degli Studi di Firenze (Italy)
Irene Costantini, European Lab. for Non-linear Spectroscopy (Italy)
Leonardo Sacconi, European Lab. for Non-linear Spectroscopy (Italy)
Paolo Frasconi, Univ. degli Studi di Firenze (Italy)
Bradley T. Hyman, MassGeneral Institute for Neurodegenerative Disease (United States)
Francesco S. Pavone, European Lab. for Non-linear Spectroscopy (Italy)
Univ. degli Studi di Firenze (Italy)


Published in SPIE Proceedings Vol. 9690:
Clinical and Translational Neurophotonics; Neural Imaging and Sensing; and Optogenetics and Optical Manipulation
Steen J. Madsen; E. Duco Jansen; Samarendra K. Mohanty; Nitish V. Thakor; Qingming Luo; Victor X. D. Yang, Editor(s)

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