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Mizrachi, J.

Publications and source records attributed to Mizrachi, J..

4 recordsLinked to original sources

High-throughput confocal airy beam oblique light-sheet tomography of brain-wide imaging at single-cell resolution

Brain research is an area of research characterized by its cutting-edge nature, with brain mapping constituting a crucial aspect of this field. As sequencing tools have played a crucial role in gene sequencing, brain mapping largely depends on automated, high-throughput and high-resolution imaging techniques. Over the years, the demand for high-throughput imaging has scaled exponentially with the rapid development of microscopic brain mapping. In this paper, we introduce the novel concept of confocal Airy beam into oblique light-sheet tomography named CAB-OLST. We demonstrate that this technique enables the high throughput of brain-wide imaging of long-distance axon projection for the entire mouse brain at a resolution of 0.26 m x 0.26 m x 1.06 m in 58 hours. This technique represents an innovative contribution to the field of brain research by setting a new standard for high-throughput imaging techniques.

neuroscience↗

Cellular Anatomy of the Mouse Primary Motor Cortex

An essential step toward understanding brain function is to establish a cellular-resolution structural framework upon which multi-scale and multi-modal information spanning molecules, cells, circuits and systems can be integrated and interpreted. Here, through a collaborative effort from the Brain Initiative Cell Census Network (BICCN), we derive a comprehensive cell type-based description of one brain structure - the primary motor cortex upper limb area (MOp-ul) of the mouse. Applying state-of-the-art labeling, imaging, computational, and neuroinformatics tools, we delineated the MOp-ul within the Mouse Brain 3D Common Coordinate Framework (CCF). We defined over two dozen MOp-ul projection neuron (PN) types by their anterograde targets; the spatial distribution of their somata defines 11 cortical sublayers, a significant refinement of the classic notion of cortical laminar organization. We further combine multiple complementary tracing methods (classic tract tracing, cell type-based anterograde, retrograde, and transsynaptic viral tracing, high-throughput BARseq, and complete single cell reconstruction) to systematically chart cell type-based MOp input-output streams. As PNs link distant brain regions at synapses as well as host cellular gene expression, our construction of a PN type resolution MOp-ul wiring diagram will facilitate an integrated analysis of motor control circuitry across the molecular, cellular, and systems levels. This work further provides a roadmap towards a cellular resolution description of mammalian brain architecture.

neuroscience↗

Super-resolution light-sheet fluorescence microscopy by SOFI.

Here we describe a new method, named LS-SOFI, that combines light-sheet fluorescence microscopy and super-resolution optical fluctuation imaging to achieve fast nanoscale-resolution imaging over large fields of view in native 3D tissues. We demonstrate the use of LS-SOFI in super-resolution analysis of neuronal structures and synaptic proteins, including cortical axons, dendritic spines, pre- and postsynaptic cytoskeletal proteins and postsynaptic AMPA receptors, in thick mouse brain sections. We also introduce an algorithm to determine the number of active fluorophore emitters detected, allowing the localization of individual molecules in LS-SOFI images. We conclude that LS-SOFI is a versatile method for fast super-resolution imaging from any tissue of the body using both commercial and custom LSFM instruments.

neuroscience↗

A High Resolution Whole Brain Imaging Using Oblique Light Sheet Tomography

Present light sheet fluorescence microscopes lack the wherewithal to image the whole brain (large tissues) with uniform illumination/detection parameters and high enough resolution to provide an understanding of the various aspects of neuroanatomy. To overcome this, we developed an oblique version of the light sheet microscope (Oblique Light Sheet Tomography, OLST) that includes a high magnification objective and serial sectioning, for volumetric imaging of the whole mouse brain at high spatial resolution at constant illumination/detection. We developed a novel gelatin based re-embedding procedure that makes the cleared brain rigid so that it can sectioned using our integrated microtome. Here, we characterize OLST and show that it can be used to observe dendritic morphology, spines and follow axons over a few mm in the mouse brain.

neuroscience↗