Optogenetic stimulation of mouse Hoxb8 microglia in specific regions of the brain induces anxiety, grooming, or both.

Previously, we have shown that either disruption of the Hoxb8 gene or ablation of a microglial subpopulation, Hoxb8 microglia, results in mice exhibiting both chronic anxiety and OCSD-like behavior, compulsive pathological hair pulling (trichotillomania), to the point of showing lesions at the sites of overgrooming. Herein we show, that optogenetic stimulation of Hoxb8 microglia in specific regions of the brain induces elevated anxiety, grooming or both. Optogenetic stimulation of Hoxb8 microglia within the dorsomedial striatum (DMS) or the medial prefrontal cortex (mPFC) induces grooming, whereas stimulation of Hoxb8 microglia in the basolateral amygdala (BLA) or central amygdala (CeA) produces elevated anxiety. Optogenetic stimulation of Hoxb8 microglia in the ventral CA1 region of the hippocampus (vCA1) induces both behaviors as well as freezing. In vitro we directly demonstrate that optogenetic stimulation of Hoxb8 microglia in specific regions of the brain activate neighboring neural activity through the induction of the c-fos-immediate early response. These experiments connect outputs from optogenetically stimulated Hoxb8 microglia, within specific regions of the brain, to the activation of neurons and neural circuits that in turn enable induction of these behaviors. These experiments suggest that Hoxb8 microglia are likely to be among, or the main, first responders to signals that evoke these behaviors. The same regions of the brain (DMS, mPFC, BLA, CeA and vCA1) have previously been defined at the neuronal level, by optogenetics, to control anxiety in mice. Intriguingly, the optogenetic experiments in microglia suggest that the two populations of microglia, canonical non-Hoxb8 and Hoxb8 microglia, function in opposition rather than in parallel to each other, providing a biological reason for the presence of two microglial subpopulations in mice.

Computational microscopy for fast widefield deep-tissue fluorescence imaging using a commercial dual-cannula probe.

A solid-glass cannula serves as a micro-endoscope that can deliver excitation light deep inside tissue while also collecting emitted fluorescence. Then, we utilize deep neural networks to reconstruct images from the collected intensity distributions. By using a commercially available dual-cannula probe, and training a separate deep neural network for each cannula, we effectively double the field of view compared to prior work. We demonstrated ex vivo imaging of fluorescent beads and brain slices and in vivo imaging from whole brains. We clearly resolved 4 µm beads, with FOV from each cannula of 0.2 mm (diameter), and produced images from a depth of ~1.2 mm in the whole brain, currently limited primarily by the labeling. Since no scanning is required, fast widefield fluorescence imaging limited primarily by the brightness of the fluorophores, collection efficiency of our system, and the frame rate of the camera becomes possible.

Fragile X: translation in action.

Fragile X is a synapsopathy--a disorder of synaptic function and plasticity. Recent studies using mouse models of the disease suggest that the critical defect is altered regulation of synaptic protein synthesis. Various strategies to restore balanced synaptic protein synthesis have been remarkably successful in correcting widely varied mutant phenotypes in mice. Insights gained by the study of synaptic plasticity in animal models of fragile X have suggested novel therapeutic approaches, not only for human fragile X but also for autism and mental retardation of unknown etiology.

Optically Transparent Thermally Insulating Silica Aerogels for Solar Thermal Insulation.

Rooftop solar thermal collectors have the potential to meet residential heating demands if deployed efficiently at low solar irradiance (i.e., 1 sun). The efficiency of solar thermal collectors depends on their ability to absorb incoming solar energy and minimize thermal losses. Most techniques utilize a vacuum gap between the solar absorber and the surroundings to eliminate conduction and convection losses, in combination with surface coatings to minimize reradiation losses. Here, we present an alternative approach that operates at atmospheric pressure with simple, black, absorbing surfaces. Silica based aerogels coated on black surfaces have the potential to act as simple and inexpensive solar thermal collectors because of their high transmission to solar radiation and low transmission to thermal radiation. To demonstrate their heat-trapping properties, we fabricated tetramethyl orthosilicate-based silica aerogels. A hydrophilic aerogel with a thickness of 1 cm exhibited a solar-averaged transmission of 76% and thermally averaged transmission of ≈1% (at 100 °C). To minimize unwanted solar absorption by O-H groups, we functionalized the aerogel to be hydrophobic, resulting in a solar-averaged transmission of 88%. To provide a deeper understanding of the link between aerogel properties and overall efficiency, we developed a coupled radiative-conductive heat transfer model and used it to predict solar thermal performance. Instantaneous solar thermal efficiencies approaching 55% at 1 sun and 80 °C were predicted. This study sheds light on the applicability of silica aerogels on black coatings for solar thermal collectors and offers design priorities for next-generation solar thermal aerogels.

Deep-brain imaging via epi-fluorescence Computational Cannula Microscopy.

Here we demonstrate widefield (field diameter = 200 µm) fluorescence microscopy and video imaging inside the rodent brain at a depth of 2 mm using a simple surgical glass needle (cannula) of diameter 0.22 mm as the primary optical element. The cannula guides excitation light into the brain and the fluorescence signal out of the brain. Concomitant image-processing algorithms are utilized to convert the spatially scrambled images into fluorescent images and video. The small size of the cannula enables minimally invasive imaging, while the long length (>2 mm) allow for deep-brain imaging with no additional complexity in the optical system. Since no scanning is involved, widefield fluorescence video at the native frame rate of the camera can be achieved.

Subunit composition and alternative splicing regulate membrane delivery of kainate receptors.

Kainate receptors (KARs) are heteromeric ionotropic glutamate receptors (GluRs) that play various roles in the regulation of synaptic transmission. The KAR subunits GluR5 and GluR6 exist under different splice variant isoforms in the C-terminal domain (GluR5a, GluR5b, GluR5c, GluR6a, GluR6b). The differential role of KAR subunit splice variants is presently unknown. In transfected COS-7 cells and neurons from wild-type and GluR5 x GluR6 mice, we have found that the subcellular localization and membrane delivery differed between these splice variants. GluR6a was highly expressed at the plasma membrane. GluR6b, GluR5a, and GluR5b were detected at lower levels in the plasma membrane and mainly colocalized with calreticulin in the endoplasmic reticulum (ER). GluR5c was strongly retained in the ER by an RXR motif. GluR6a acted as a key subunit splice variant promoting surface expression of ER-retained subunit splice variants when assembled in heteromeric KARs. Surface expression of GluR6a was independent of its PDZ (postsynaptic density-95/discs large/zona occludens-1) binding motif and was promoted by a stretch of four basic amino acid residues at its C terminus. Overall, splice variants and subunit composition of KARs regulate receptor trafficking from the endoplasmic reticulum to the plasma membrane.