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The authors present a new computational approach to automatically annotate, analyze, visualize and easily share whole-brain datasets at cellular resolution, based on a scale-invariant and interactive mouse brain reference atlas. The authors applied this framework to define the organization and cocaine-induced activity of corticostriatal circuits.
The authors develop a methods suite for millisecond-precise, single-cell-resolution control of neural activity through protein engineering of novel opsin/trafficking sequence combinations, as well as optimized holographic two-photon optics.
To what extent are population-level results an expected byproduct of simpler structure already known to exist in single neurons? Conventional controls are insufficient to perform this critical investigation. The authors developed a methodological framework to test the significance of population-level studies and apply it to prefrontal and motor cortices.
The authors report two new engineered AAV capsids that efficiently deliver genes throughout the adult central and peripheral nervous systems after intravenous administration. Complementing these capsids is an AAV toolbox that enables cell morphology and genetic manipulation studies of defined neural cell types in transgenic or wild-type animals.
The authors demonstrate that optical fibers with tapered tips can homogenously illuminate either elongated brain structures or dynamically selected subregions. Tapered fibers achieve efficient optogenetic stimulation in vivo with minimal tissue damage. In addition, a single fiber can deliver light of multiple wavelengths to independently controlled regions.
No techniques exist for the precise identification of vascular pericytes. Here the authors identify and characterize a fluorescent dye that exclusively labels pericytes. Using this tool for intravital imaging of the mouse brain, the authors provide conclusive evidence that these cells are molecularly and functionally distinct from all other brain and vascular cells.
Pandya et al. describe a protocol to differentiate human and mouse iPSCs into cells with the phenotype, transcriptional profile and functional properties of microglia. The treatment of murine intracranial malignant gliomas with these cells demonstrates their potential clinical use. These microglia-like cells will enable further studies into the role of microglia in health and disease.
The authors built a simple optical module that generates axially extended Bessel foci, optimized for in vivo brain imaging. Easily incorporated into existing two-photon fluorescence microscopes, this module allowed 30-Hz volumetric functional imaging of sparsely labeled brains at synaptic resolution in a variety of model organisms in vivo.
The authors use fiber-based fabrication to create flexible biocompatible probes with integrated optical, electrical and microfluidic capabilities. Functionality is demonstrated by characterizing the temporal dynamics of opsin expression following viral delivery, long-term tracking of individual neuron action potentials and modulation of neural circuits in the context of mouse behavior.
