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Biology subjects

Carey, H.

Publications and source records attributed to Carey, H..

7 recordsLinked to original sources

An interactive 3D atlas of gene expression in the mouse brain

The Allen Mouse Brain Atlas provides gene expression data for over 20,000 genes and has been extensively used in neuroscience. However, its constrained by a resolution of 200 {micro}m3. We improved this to 25 {micro}m3 for 4,083 genes by re-registering 401,660 sections to atlas space. From this, we produced an atlas with regions defined by shared molecular signatures and built an interactive online platform allowing exploration of gene expression patterns.

neuroscience↗

Software and pipelines for registration and analyses of rodent brain image data in reference atlas space

Advancements in methodologies for large-scale acquisition of high-resolution serial microscopy image data have opened new possibilities for experimental studies of cellular and subcellular features across whole brains in animal models. There is a high demand for open-source software and workflows for automated or semi-automated analysis of such data, facilitating anatomical, functional, and molecular mapping in healthy and diseased brains. These studies share a common need to precisely identify, visualize, and quantify the location of observations within anatomically defined regions, ensuring consistent and reproducible interpretation of anatomical locations and thereby allowing meaningful comparisons of results across multiple independent studies. Addressing this need, we have developed a suite of desktop and web-applications for registration of serial brain section images to three-dimensional brain reference atlases (QuickNII, VisuAlign, WebAlign, WebWarp, and DeepSlice) and for performing data analysis in a spatial context provided by an atlas (Nutil, QCAlign, SeriesZoom, LocaliZoom, and MeshView). The software can be utilized in various combinations, creating customized analytical pipelines suited to specific research needs. The web-applications are integrated in the EBRAINS research infrastructure and coupled to the EBRAINS data platform, establishing the foundation for an online analytical workbench. We here present our software ecosystem, exemplify its use by the research community, and discuss possible directions for future developments.

bioinformatics↗

An extended and improved CCFv3 annotation and Nissl atlas of the entire mouse brain

Brain atlases are essential for quantifying cellular composition in mouse brain regions. The Allen Institutes Common Coordinate Framework version 3 (CCFv3) is widely used, delineating over 600 anatomical regions, but it lacks coverage for the most rostral and caudal brain parts, including the main olfactory bulb, cerebellum, and medulla. Additionally, the CCFv3 omits key cerebellar layers, and its corresponding Nissl-stained reference volume is not precisely aligned, limiting its utilisability. To address these issues, we developed an extended atlas, the Blue Brain Project CCFv3 augmented (CCFv3aBBP), which includes a fully annotated mouse brain and an improved Nissl reference aligned in the CCFv3. This enhanced atlas also features the central nervous system annotation (CCFv3cBBP). Using this resource, we aligned 734 Nissl-stained brains to produce an average Nissl template, enabling an updated distribution of neuronal soma positions. These data are available as an open-source resource, broadening applications such as improved alignment precision, cell type mapping, and multimodal data integration.

bioinformatics↗

DeMBA: a developmental atlas for navigating the mouse brain in space and time

Studies of the adult mouse brain have benefited from three-dimensional (3D) atlases providing standardised frameworks for data analysis and integration. However, few 3D atlases exist for the developing mouse brain, and none cover more than a few ages. This fails to represent the dynamic nature of development and is insufficient for researchers whose data fall between the ages of existent atlases. Existing atlases also neglect the spatial correspondence between ages, making comparison across ages difficult. We present the Developmental Mouse Brain Atlas (DeMBA), a 4D atlas encompassing every postnatal day from 4 to 56. DeMBA is incorporated in software for spatial registration and analysis, enabling brain-wide quantification of features of interest. Furthermore, we provide a software package, the CCF translator, allowing coordinates or image volumes to be transformed between ages for comparison. These resources provide age-specific spatial frameworks incorporated in accessible analytic pipelines for developmental mouse brain data.

neuroscience↗

The developing mouse dopaminergic system: Cortical-subcortical shift in D1/D2 receptor balance and increasing regional differentiation

The dopaminergic system of the brain is involved in complex cognitive functioning and undergoes extensive reorganization during development. Yet, these changes are poorly characterized. We have quantified the density of dopamine 1- and 2-receptor (D1 and D2) positive cells across the forebrain of male and female mice at five developmental stages. Our findings show a cortico-subcortical shift in D1/D2 balance, with increasing D1 dominance in cortical regions as a maturational pattern that occurs earlier in females. We describe postnatal trajectories of D1 and D2 cell densities across major brain regions and observe increasing regional differentiation of D1 densities through development. Our results provide the most comprehensive overview of the developing dopaminergic system to date, and an empirical foundation for further experimental and computational investigations of dopaminergic signaling.

neuroscience↗

DeepSlice: rapid fully automatic registration of mouse brain imaging to a volumetric atlas

Registration of data to a common frame of reference is an essential step in the analysis and integration of diverse neuroscientific data modalities. To this end, volumetric brain atlases enable histological datasets to be spatially registered and analysed, yet accurate registration remains expertise-dependent and slow. We have trained a neural network, DeepSlice, to register mouse brain histology to the Allen Brain Atlas, retaining accuracy while improving speed by >1000 fold.

neuroscience↗

An executive center for the intake of liquids

It has long been known that orofacial movements for feeding can be triggered, coordinated, and often rhythmically organized at the level of the brainstem, without input from higher centers. We uncover two nuclei that can organize the movements for ingesting fluids in mammals. These neuronal groups, defined by unique transcriptional codes and developmental origins, IRtPhox2b and Peri5Atoh1, are located, respectively, in the intermediate reticular formation of the medulla and around the motor nucleus of the trigeminal nerve. They are premotor to all jaw-opening and tongue muscles. Stimulation of either, in awake animals, opens the jaw, while IRtPhox2b alone also protracts the tongue. Moreover, stationary stimulation of IRtPhox2b entrains a rhythmic alternation of tongue protraction and retraction, synchronized with jaw opening and closing, that mimics lapping. Finally, fiber photometric recordings show that IRtPhox2b is active during volitional lapping. Our study identifies one of the long hypothesized subcortical nuclei underpinning a stereotyped feeding behavior.

neuroscience↗