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Open AccessJournal ArticleDOI

Miniaturized integration of a fluorescence microscope

TLDR
A miniature (1.9 g) integrated fluorescence microscope made from mass-producible parts, including a semiconductor light source and sensor enables high-speed cellular imaging across ∼0.5 mm2 areas in active mice and allows concurrent tracking of Ca2+ spiking in >200 Purkinje neurons across nine cerebellar microzones.
Abstract
The light microscope is traditionally an instrument of substantial size and expense. Its miniaturized integration would enable many new applications based on mass-producible, tiny microscopes. Key prospective usages include brain imaging in behaving animals for relating cellular dynamics to animal behavior. Here we introduce a miniature (1.9 g) integrated fluorescence microscope made from mass-producible parts, including a semiconductor light source and sensor. This device enables high-speed cellular imaging across ∼0.5 mm2 areas in active mice. This capability allowed concurrent tracking of Ca2+ spiking in >200 Purkinje neurons across nine cerebellar microzones. During mouse locomotion, individual microzones exhibited large-scale, synchronized Ca2+ spiking. This is a mesoscopic neural dynamic missed by prior techniques for studying the brain at other length scales. Overall, the integrated microscope is a potentially transformative technology that permits distribution to many animals and enables diverse usages, such as portable diagnostics or microscope arrays for large-scale screens.

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Imaging Calcium in Neurons

TL;DR: This Primer briefly reviews the general mechanisms of neuronal calcium signaling, and introduces the calcium imaging devices, including confocal and two-photon microscopy as well as miniaturized devices used in freely moving animals.
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Long-term dynamics of CA1 hippocampal place codes

TL;DR: Using Ca2+ imaging in freely behaving mice that repeatedly explored a familiar environment, thousands of CA1 pyramidal cells' place fields over weeks were tracked to preserve an accurate spatial representation across weeks.
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Neuronal cell-type classification: challenges, opportunities and the path forward

TL;DR: In this paper, a staged approach for cell type classification in the brain is proposed, including the incorporation of multiple, quantitative features as criteria, the use of discontinuous variation to define types and the creation of a hierarchical system to represent relationships between cells.
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Genetically encoded indicators of neuronal activity

TL;DR: This review describes and assess different classes of fluorescent protein indicators of neural activity and focuses on how indicator characteristics relate to their use in living animals and on likely areas of future progress.
References
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Systematic Review: Process of Forming Academic Service Partnerships to Reform Clinical Education

TL;DR: This study’s findings can provide practical guidelines to steer partnership programs within the academic and clinical bodies, with the aim of providing a collaborative partnership approach to clinical education.
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A pyramid approach to subpixel registration based on intensity

TL;DR: An automatic subpixel registration algorithm that minimizes the mean square intensity difference between a reference and a test data set, which can be either images (two-dimensional) or volumes (three-dimensional).
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Imaging neural activity in worms, flies and mice with improved GCaMP calcium indicators

TL;DR: A single-wavelength GCaMP2-based GECI (GCaMP3) is developed, with increased baseline fluorescence, increased dynamic range and higher affinity for calcium, and long-term imaging in the motor cortex of behaving mice revealed large fluorescence changes in imaged neurons over months.
Book

The Nature of Technology: What it Is and How it Evolves

TL;DR: In "The Nature of Technology", ground-breaking economist W. Brian Arthur explores the extraordinary way in which the technology that surrounds us and allows us to live our modern lives has actually been developed.
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