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(c) Sectional images of AVcoarse shown in NIH color scheme. 4e). To create it, researchers averaged brain images from 1,675 mice, generating a high . Four FAAs with different total ROI counts were constructed for the present study to demonstrate its flexibility: FAAbase (total node count: 866, leaf node count: 669; Fig. Department of Neuropsychiatry, Keio University School of Medicine, 35 Shinanomachi, Shinjuku, Tokyo, 160-8582, Japan, Norio Takata,Nobuhiko Sato&Kenji F. Tanaka, Central Institute for Experimental Animals (CIEA), 3-25-12, Tonomachi, Kawasaki, Kanagawa, 210-0821, Japan, Department of Physiology, Keio University School of Medicine, 35 Shinanomachi, Shinjuku, Tokyo, 160-8582, Japan, You can also search for this author in 3a). The procedure dividing a leaf node was performed with Python codes and user-specified text-based information related to (1) IDs for brain structures to be divided, (2) brain structure acronyms for source and target of axonal fiber innervation, and (3) experimental IDs found at a website of AIBS for gene expression (https://mouse.brain-map.org/) and axonal fiber projection (http://connectivity.brain-map.org/) (Fig. Sci. Fig. Among the nodes, 5% (16 leaf nodes) passed the second criterion. L denotes the left side of the brain. Spatial averaging of fMRI images using a Gaussian kernel was not used for this study because the isotropic characteristics of the kernel did not reflect an actual spatial distribution of brain structures, which might result in contamination of blood oxygenation level-dependent (BOLD) fMRI signals from other nodes, especially in a thin but large node such as a cortical layer (Fig. Article Matsui, T., Murakami, T. & Ohki, K. Transient neuronal coactivations embedded in globally propagating waves underlie resting-state functional connectivity. A volume image of the gene-expression energy of a gene Wfs-1 was retrieved from AIBS (Fig. The fourth, gene expression volume, was prepared with genome-wide in situ hybridization (ISH) image for approximately 20,000 genes in adult mice21. Rep. 8, 14406 (2018). Hum. In addition, the original AT by AIBS is based on samples that are larger than commonly available TPMs (60 specimens). Hikishima, K. et al. Combining all descendant nodes of SS was necessary to maintain the anatomical hierarchy. Finally, the fifth, the axonal fiber projection volume, was constructed with serial two-photon tomography using viral tracers for 2995 axonal pathways22,23. These leaf nodes are destructive because combining them in the AO to construct a new leaf node does not change the AV and thereby break one-on-one correspondence between the AO and AV. Obtained funding: N.T., K.F.T. Today, the common coordinate framework version 3 developed by the Allen's Institute of Brain Science (AIBS . 316, 314347 (1992). The anatomical hierarchy defined in AO was visualized as rooted tree graphs (e.g. FAA consists of a JSON-formatted text file (anatomical ontology, AO) and a three-dimensional volume file of the mouse brain (annotation volume, AV). 40, 329339 (2019). Furthermore, finally, 81% (13 leaf nodes) passed the last criterion. Sci. (b) Bar graphs comparing FCs from the divided nodes in CA1 or CP in the left hemisphere. Marion D Almeida Ecole Normale Suprieure de Paris Horizontal mouse brain atlas with cortical layers ? Enhanced and unified anatomical labeling for a common mouse brain atlas, Integration of gene expression and brain-wide connectivity reveals the multiscale organization of mouse hippocampal networks, neuromaps: structural and functional interpretation of brain maps, Imaging-based parcellations of the human brain, A Robust Image Registration Interface for Large Volume Brain Atlas, A consensus protocol for functional connectivity analysis in the rat brain, An Open MRI Dataset For Multiscale Neuroscience, A multi-scale probabilistic atlas of the human connectome, https://github.com/ntakata/flexible-annotation-atlas/tree/master/FAAs, https://mouse.brain-map.org/static/brainexplorer, https://www.mathworks.com/matlabcentral/fileexchange/27418-fdr_bh, http://atlas.brain-map.org/atlas?atlas=1#atlas=1&structure=465&resolution=10.87&x=4560.044008725649&y=3727.8479489413176&zoom=-3&plate=100960348, https://github.com/ntakata/flexible-annotation-atlas, http://help.brain-map.org/display/mouseconnectivity/Documentation, http://help.brain-map.org/display/mousebrain/API, https://portal.brain-map.org/latest-data-release, https://doi.org/10.1016/j.neuroimage.2017.11.002, https://www.janelia.org/project-team/mouselight, http://creativecommons.org/licenses/by/4.0/. This is an expanded view of the FC matrix (a) for the primary somatosensory area for barrel cortex (SSp-bfd). and JavaScript. Yu, X., Qian, C., Chen, D., Dodd, S. J. (d) This icicle plot presents the anatomical hierarchy of brain structures in FAAbase. an inner node A. & Mintun, M. A. Resting-state functional MRI in depression unmasks increased connectivity between networks via the dorsal nexus. Further investigation must be conducted to assess, interpret, and validate laminar FC analysis of fMRI data using thin but large nodes in FAA. To visualize the FC distribution explicitly with anatomical hierarchy, FCs from one of the 13 leaf nodes, Retrosplenial area, ventral part, layer 2/3_L (RSPv2/3_L; node size, 518 nL), were represented as CoSE representation in Fig. For more detailed maps based on newer satellite and aerial images switch to a detailed map view. Flexible annotation atlas of the mouse brain: combining and dividing brain structures of the Allen Brain Atlas while maintaining anatomical hierarchy, https://doi.org/10.1038/s41598-021-85807-0. . 1b). Actually, FC analysis was restricted to nodes for brain parenchyma excluding nodes for fiber tracts and ventricles that were also defined in FAA. Brain Mapp. Online public resources by AIBS used for construction of FAA included a text file for annotation ontology (AO; Fig. Google Scholar. According to a thresholding histogram of the axonal projection density in a leaf node CP (Fig. Consequently, sharing of whole brain ROI definition among laboratories would be facilitated through text-based information. The proximal and functional relationship of SSp and SSs . 2 and 3). A stereotaxic MRI template set of mouse brain with fine sub-anatomical delineations: Application to MEMRI studies of 5XFAD mice. For example, an inner node STR in the original AO (Fig. 1) was substituted for a tissue probability map (TPM) based on image intensity of structural MRI9,30,31,32. High-quality photomicrographs of brain sections are depicted in . Upper panels: coronal sections of volume data obtained at AIBS for gene-expression energy of a gene Wfs-1 (c) or axonal projection-density from the insula cortex to CP (d). Front. 4a). A zoomable visualization of anatomical hierarchy of the brain structures in AO is provided as an HTML file using D3.js (https://d3js.org/) (e.g. FAAbase is single-sided: homotopic areas on the right and left sides of the brain have the same ID and constitute a single node (Fig. Van Essen, D. C. Windows on the brain: The emerging role of atlases and databases in neuroscience. 17, 143155 (2002). It is noteworthy that such layer-specific FC was observed both in the dorsal (e.g. (c) Distribution of size (voxel count in AVbase) of leaf nodes in FAAbase (blue plots). Axonal projection data were flipped horizontally to obtain symmetrical projection data before thresholding. Cortical dendritic activity correlates with spindle-rich oscillations during sleep in rodents. Neuroimage 53, 365372 (2010). For example, in the primary somatosensory area (barrel field in the left cortex; SSp-bfd), supragranular (L1 and 2/3) and infragranular (L5, 6a, and 6b) layers showed higher FC within them, but lower FC between them (Fig. Concretely, structural MRI images in NIfTI format underwent the following: (1) N4 bias-field corrected by ANTs; (2) skull-stripped with a BET plugin in Multi-image Analysis GUI software (Mango v4.1 [1531]); (3) replicated with copying s-form code to q-form code about image orientation in a NIfTI header of the images because the BET procedure deleted q-form code; and (4) deformably registered to the original AT from AIBS in NIfTI format in RAS orientation by ANTs (antsRegistrationSyNQuick.sh). Smith, S. M. Fast robust automated brain extraction. Simultaneous mesoscopic and two-photon imaging of neuronal activity in cortical circuits. Provided by the Springer Nature SharedIt content-sharing initiative. Article Sci. An ontologically consistent MRI-based atlas of the mouse diencephalon. The combining leaf nodes procedure was performed by editing the AObase text file (Fig. Natl. Earlier investigations of hierarchical organization of resting-state FC have specifically examined leaf nodes39,40; consequently, modulation of FC across the anatomical hierarchy has been little investigated because examination of inner nodes was necessary. 10, 5504 (2019). Neuroinform. Denoising of the fMRI time series was conducted using a functional connectivity toolbox (CONN 18.b). MouseLight. Projection Mapping image data detailing axonal projections labeled by viral tracers. Rep. 7, 85 (2017). Third is reproducibility: combination and division of nodes were performed objectively by the codes using text-based information. Neuroimage 146, 118 (2017). Acad. Internet Explorer). Among the FCs, 88.7% (203 among 229 FCs) were significantly larger for the ventral CA1 than the dorsal one (n=13, paired t test with FDR adjusted p value of 0.05; blue markers at the top of Fig. Ellipses and rectangles respectively denote leaf nodes and inner nodes. In fact, multicenter comparison of resting-state fMRI on the mouse brain has not been reported until this year33. Various three-dimensional annotation volumes (AVs) for the mouse brain have been proposed with various spatial resolution (32156m), numbers of animals for averaging (427 animals), and numbers of segmented structures (570, and 707 regions-of-interest, ROIs)4,5,6,7,8,9,10,11. Dashed line: an inflection point of the fitted curve used as a threshold. Fan, J. et al. Leaf nodes CA1 and CP were divided, respectively, to two by the thresholds, resulting in nodes CA1_geneH (red) and CA1_geneL (blue) and CP_fiberH (red) and CP_fiberL (blue). 1a middle). These were collectively designated as FAAdetailed, which had a total node count of 1381, among which 1097 and 284 were leaf nodes and inner nodes, respectively (Fig. This original AV is single-sided: homotopic brain structures on the left and right sides of the brain have the same ID and constitute a single node. One exception to this point was found in the prefrontal cortex (PFC; arrows in Fig. Study concept and design: N.T. Navigate the high-resolution 2-D ISH images using the 3-D model. Construction of FAA takes just two steps, combining and dividing brain structures, using user-specified, text-based information and Python codes. Significant difference in FC within vs. between supra-granular and infra-granular layers was found in the most cortical regions. They are also destructive because the size (voxel count) of these inner nodes changes depending on whether they are inner nodes or leaf nodes, resulting in node size inconsistency. Dominance of blue markers over red ones suggests stronger FCs from the ventral CA1 than that from the dorsal CA1. Using a computational framework designed to . Fig. Resting-state FC was calculated using FAAdetailed (Fig. Processing pipeline using the Allen brain atlas has been reported for cross-modal comparisons among anatomical MRI, diffusion tensor imaging (DTI), and fMRI19. CAS 2b,c), and FAAdetailed (1381, 1097; Fig. 2d and 4a,b. Proc. Presuming that FC from a source leaf node S to an inner node A is larger than FC to descendant leaf nodes (b,c) of the inner node A, which is not an ancestor node of the source node S, then this situation suggests a mechanism to modulate FC in larger units in the brain, i.e. Actually, FAA presents three advantages. Commun. FAA facilitates integration of these data with open source resources for which datasets are registered to the Allen Brain Atlas65,66, thereby promoting cellular level whole-brain investigation67. an inner node, that occupies a higher position in the anatomical hierarchy than leaf nodes occupy. Circles and squares respectively represent leaf nodes and inner nodes. Here, a detailed protocol for a successful preparation of vibratome-cut horizontal hippocampal slices of mouse brains is provided. Whereas high FC was found between leaf nodes in the right and left PFC (arrows) such as PL, ILA, and ORB, low FC was observed between the leaf nodes and inner nodes such as CTXpl and Isocortex (arrowheads). volume11, Articlenumber:6234 (2021) Then, destructive inner nodes in the AO were classified to two nodes: (1) an inner node without corresponding voxels in the original AV, and (2) a new leaf node with corresponding voxels in the AV (Fig. AVbase was updated to AVcoarse by reflecting AOcoarse. Janelia Research Campus. 1c) accounted for 6.7% of all leaf nodes in FAAbase (45 out of 669 leaf nodes). As one example, the node size of Frontal pole, layer 6b was only 2 nL (2 voxels in AVbase). 1a right), icicle plots (e.g. The FC matrix showed conspicuous vertical and horizontal red bands, suggesting that inner nodes, which are higher in the anatomical hierarchy in the brain, typically had higher FC in the cortex (Fig. Google Scholar. Glia 66, 20132023 (2018). CAS Data sharing and the future of science. FAA enables analysis of resting-state functional connectivity (FC) across the anatomical hierarchy because FAA retains information related to the hierarchy. 3). different IDs were assigned to homotopic nodes in the left and right side of the brain by adding a constant value to IDs on the right side of the brain (Fig. Latest Data Releasebrain-map.org. Ellipses and rectangles respectively denote leaf nodes and inner nodes. View Atlas Mouse Spinal Cord Atlas A detailed atlas of gene expression across the adult and juvenile mouse spinal cord. In this regard, destructive nodes exist in the original AO, which might impair the structure of the anatomical hierarchy in the AO and which might break consistency between AO and AV upon combining or dividing nodes (see step 2 in Supplementary Table 3) (Destructive nodes relate to nodes in CCF version 2 which were grouped for CCFv3. http://help.brain-map.org/display/mouseconnectivity/Documentation (2017). Briefly, an acrylic head bar (3327 mm3) was mounted using dental cement (Super-Bond C&B; Sun Medical Co., Ltd., Shiga, Japan) along the sagittal suture of the exposed skull of seven male C57BL/6J mice anesthetized with 23% isoflurane. Note that 1 nL corresponds to a single voxel (100100100 m3) of a volume data (AT and AV). 3a). Dorr, A. E., Lerch, J. P., Spring, S., Kabani, N. & Henkelman, R. M. High resolution three-dimensional brain atlas using an average magnetic resonance image of 40 adult C57Bl/6J mice. Methods 73, 417 (2015). PubMed Central Heart&Brain Warsaw Advertising Services Warsaw, Mazowieckie 561 followers We are group of companies that link creativity and data. PubMed Neuropsychopharmacology 36, 20092017 (2011). These steps were performed objectively using Python codes while maintaining (1) anatomical hierarchy defined in AO, and (2) consistency between AO and AV. Specifically, FC between inner nodes, and FC between a leaf node and an inner node were examined, in addition to conventional FC between leaf nodes (Fig. Google Scholar. Each node is shown with its acronym and size in units of nL. 1b; see the first section of Results for destructive). Cite this article. Uree Chon, Daniel J. Vanselow, Yongsoo Kim, Ross M. Lawrence, Eric W. Bridgeford, Joshua T. Vogelstein, Michael S. Bienkowski, Ian Bowman, Hong-Wei Dong, Ross D. Markello, Justine Y. Hansen, Bratislav Misic, Simon B. Eickhoff, B. T. Thomas Yeo & Sarah Genon, Joanes Grandjean, Gabriel Desrosiers-Gregoire, Andreas Hess, Jessica Royer, Ral Rodrguez-Cruces, Boris C. Bernhardt, Yasser Alemn-Gmez, Alessandra Griffa, Patric Hagmann, Scientific Reports Experimental methods and procedures have been . A tool by Matt Gaidica These anatomical reference atlases illustrate the developing mouse brain, covering seven stages of embryonic (E) and postnatal (P) development. 2d), they showed low FC with inner nodes such as the isocortex and cortical plate (CTXpl) (pale red area indicated by arrowheads in Fig. To achieve creation, it is crucially important to maintain consistency between AV and AO. The ip . 1d), FAAsegment (4, 3; Supplementary Fig. This situation suggests a mechanism to modulate FC in larger units in the brain, i.e. Complete data sets available for several vertebrate species. In vivo morphometric analysis of vision-related brain structures. Neuron 94, 1085-1100.e6 (2017). We hybridized 75 coronal sections from one brain hemisphere that covered the entire AP axis onto ST arrays ( Fig. All descendant nodes of an inner node should be combined to make the inner node a new leaf node. Foundations of layer-specific fMRI and investigations of neurophysiological activity in the laminarized neocortex and olfactory bulb of animal models. Specifically, FC between L1 and L2/3 or between L5 and L6a was significantly larger than FC between L2/3 and L6a. Neurosci. Google Scholar. This higher FC is evident in vertical and horizontal red bands in the FC matrix, demonstrating high FCs between inner nodes and between an inner node and a leaf node in the cerebral cortex. 20, 742749 (2018). A histogram of correlation coefficients in the FC matrix by FAAcoarse confirmed the tendency for higher FC in inner nodes (Fig. This all-or-none rule for combining descendant nodes was necessary to maintain consistency of anatomical hierarchy in FAA. J. Comp. Structural and functional MRI datasets used for this study are publicly available in the Brain Imaging Data Structure (BIDS) format at OpenNeuro (project ID: Mouse_rest_awake, https://openneuro.org/datasets/ds002551). source leaf node and an inner node that satisfies the situation described below in (c). For this study, each brain structure was regarded as a node in a graph theoretical term. Structural and functional MRI was performed using a 7.0T MRI apparatus equipped with actively shielded gradients at 700 mT/m maximum strength (Biospec 70/16; Bruker BioSpin AG, Fllanden, Switzerland) with a cryogenically cooled 2-ch transmit/receive phased array surface coil (CryoProbe, Z120046; Bruker BioSpin AG, Fllanden, Switzerland) and a ParaVision 6.0.1 software interface (Bruker Biospin AG, Fllanden, Switzerland). 1b). FAAbase is also single-sided. In all, 13 runs of T2* weighted fMRI were obtained using 7 mice with a gradient-echo echo-planar imaging (EPI) sequence (TR/TE=1500/15ms; N segments=1; BW=250kHz; flip angle=70; FOV=19.219.2 mm2; matrix=646418; number of slices=18; slice thickness=0.70mm; slice gap=0.05mm; spatial resolution=200200750 m3; temporal resolution=1.5s; dummy scan=0; number of repetitions=400; scan time=10min). 2). Numerous patterns of FAA can then be constructed using two steps with user-specified text-based information: (1) combining leaf nodes of FAAbase to produce a new leaf node with larger size, i.e. This satellite map of Warsaw is meant for illustration purposes only. Imaging 57, 8394 (2019). 1a middle). The divided nodes were visible in AVdetailed (arrows and arrowheads in Fig. 3d right histogram), the nodes were classifiable into two types: nodes with lower and higher projection density CP_fiberL and CP_fiberH, respectively (blue and red areas in Fig. Li, A. et al. combinations and divisions of ROIs for brain structures were not implemented, leading to inconsistent ROIs among laboratories for MRI in the mouse brain. Sakata, S. & Harris, K. D. Laminar structure of spontaneous and sensory-evoked population activity in auditory cortex. Imaging Biol. PLoSOne 10, e0121417 (2015). Reson. Rev. Kovaevi, N. et al. 3d). Representative projection data are depicted in Fig. Prenatal Mouse Brain Atlas Color images and annotated diagrams of: Gestational Days 12, 14, 16 and 18 Sagittal, coronal and horizontal section Home Book Authors: Uta Schambra Complete mapping of the developing mouse brain Features imaging of whole brain sections Includes DVD with color images Includes supplementary material: sn.pub/extras Sci Rep 11, 6234 (2021). Front. Article Aggarwal, M., Zhang, J. 1d), which is indispensable to decide which brain structures to be combined or not. Article 98, 18 (2015). Mouse Brain Atlas ML mm AP mm DV mm Rat Brain Atlas CPu caudate putamen (striatum) Coronal Sagittal Atlas Source: Paxinos, George, and Keith B.J. Similarly, there were 196 significant FCs from a node CP_fiberH (ventral CP) and/or a node CP_fiberL (dorsal CP) in the FC matrix (n=13, paired t tests with FDR adjusted p value of 0.05). 1d), or a compound spring embedder (CoSE) layout (Fig. combination and division of nodes were not implemented. A brain atlas is necessary for analyzing structure and function in neuroimaging research. AIBS provides a three-dimensional anatomical template (AT), annotation volume (AV), and a text file for anatomical ontology (AO) of the mouse brain (Fig. Color code at the bottom represents brain structures. Natl. (a) Resting-state FC matrix calculated with FAAdetailed. Specifically, destructive leaf nodes in the original AO were first eliminated, as were leaf nodes isl and OT1 in the AO (Fig. Commun. PubMed Central 4a denote pairs of a leaf node and an inner node that satisfied the criteria. 4e). 3). 3d bottom panels). Acquisition of data: N.T. Considering the huge amount of public resources provided by AIBS related to gene expression and axonal projection, the proposed FAA pipeline can prepare innumerable patterns of an annotation atlas that would meet the various needs of researchers. 33, 2027 (2009). Similarly, a node FRP is a parent node of its child nodes FRP1 and FRP2/3. & Carpenter, T. A. Voxel-based morphometry in the R6/2 transgenic mouse reveals differences between genotypes not seen with manual 2D morphometry. Furthermore, cortical layer-specific FC was examined using FAA that had thin but large ROIs for cortical layers. 1d). Parameter tuning was performed before MRI acquisition: (1) manual tuning and matching of radiofrequency (RF) coils (wobble adjustment), (2) automatic adjustment of the resonance frequency (basic frequency), (3) calibrating the RF pulse power (reference power), (4) adjusting global linear shims (FID shim), (5) measuring a B0 map, and (6) localized field-map shimming based on a B0 map (MAPSHIM; repetition time [TR]=20ms; echo time [TE]=1.520ms, 5.325ms; spatial resolution=300300300 m3; matrix=646464 voxels). Yoshida, K. et al. An icicle plot depicts the anatomical hierarchy of brain structures in AObase (Fig. High-speed and scalable whole-brain imaging in rodents and primates. An increasing number of studies have used the Allen mouse brain atlas for analyzing MRI data17,18,19,20. 4d. When the inner node STR becomes a leaf node by combining its child nodes such as CP and OT (Fig. sagittal, and horizontal levels in E-T. (C,D) Lateral views of the final reconstruction of LGd into 3 subdivisions; shell, core, and ipsilateral projection zone (ip). Administrative, technical, and material support: Y.K., H.O., K.F.T. A mere two-step procedure with user-specified, text-based information and Python codes constructs FAA with nodes which can be combined or divided objectively while maintaining anatomical hierarchy of brain structures. A mesoscale connectome of the mouse brain. 112, 1003210037 (2015). 1c). The four FAAs are also available. Irrespective of the negative result, FC across the anatomical hierarchy is worthy of further investigation during, say, a situation with large-scale brain dynamics such as cortical spreading depression45. Actually, FAA enabled FC analysis across the anatomical hierarchy, such as FC between inner nodes, and FC between an inner node and leaf nodes, in addition to conventional FC between leaf nodes because FAA retains information related to anatomical hierarchy of brain structures (Standard FC analysis particularly addressing leaf nodes using the same MRI dataset is described in our earlier paper33.). Grandjean, J. et al. The interactive ontology and viewer for the coronal mouse brain atlas, related to Figure 7. Their download links are presented in Supplementary Table 1. Cortical-layer-specific FC analysis was attempted using FAAdetailed because thin but large nodes for cortical layers were defined in it. Find 8837 researchers and browse 127 departments, publications, full-texts, contact details and general information related to Warsaw University of Technology | Warsaw, Poland | A. et al. Key features. The leaf node size distribution in FAAcoarse confirms that every node was larger than a single voxel of fMRI, although approximately 20% of leaf nodes were left extremely large (>10,000 nL) (red symbols in Fig. 2d). & Koretsky, A. P. Deciphering laminar-specific neural inputs with line-scanning fMRI. FAAcoarse was constructed as double-sided, i.e. All animal experiments were conducted in accordance with the National Institutes of Health Guide for Care and Use of Laboratory Animals (NIH Publications No. . For nodes with collapsed letters, see the zoomable HTML version of this plot at https://github.com/ntakata/flexible-annotation-atlas/tree/master/FAAs. One limitation of the proposed FAA is that combining a part of sibling nodes is not allowed in FAA construction. 1b left). Google Scholar. Even overly small nodes were reserved if their large sibling nodes were intended for use in additional analysis. Divided nodes for CA1 (arrows) and CP (arrowheads) on both sides of the brain are shown. Dr. Luis Puelles used a custom developmental taxonomy for annotation of the Allen Developing Mouse Brain Reference Atlases. Commun. Spatial coordinates of three-dimensional volume data at AIBS adopt CCFv3, enabling integration of multimodal resources by AIBS on (1) an anatomical template of the mouse brain (AT), (2) annotation volume (AV), (3) gene expression, and (4) axonal fiber projection. J. Neurosci. An interactive framework for whole-brain maps at cellular resolution. To obtain Application of FAA is not limited to fMRI data. This standard procedure in in vivo two-photon imaging for awake mice achieves stable measurements of brain activity over several hours26,27 while avoiding confounding effects of anesthetics during fMRI because anesthesia is not necessary to place awake mice in an animal bed of MRI28. Kuan, L. et al. Blue Brain Portal. A three-dimensional MRI Atlas of the mouse brain with estimates of the average and variability. However, the difference of FC was not always significant. Combining or dividing nodes in the AV according to the anatomical hierarchy defined in the AO enabled creation of various AVs with arbitrary counts of nodes while maintaining the hierarchy. For example, an inner node STR in the original AO has corresponding voxels of 1392 nL in the original AV (Fig. Article Horizontal Hippocampal Slices of the Mouse Brain J Vis Exp. Nodes smaller than a single voxel in fMRI (30 nL; dashed line in Fig. The Allen reference atlas: A digital color brain atlas of the C57Bl/6J male mouse. It fills an urgent need for a comprehensive atlas of the developing mouse brain for use in studies of both normal and abnormal development. PubMed The multimodal atlas framework includes three mouse brain templates: an MRI template, a serial two-photon microscopy (STPT) template (Wang et al., 2020a, b) from Mouse Brain Common Coordinate Framework version 3 (CCFv3) by Allen Institute of Brain Science (AIBS), and an LSFM template (Perens et al., 2021 ). This report presents a pipeline to construct a flexible annotation atlas (FAA) for the mouse brain, for which brain structures can be combined or divided objectively using resources by AIBS on gene expression and fiber projection. Every leaf node and inner node in AO should and should not have corresponding voxels in AV, respectively. Steiner, H. & Van Waes, V. Addiction-related gene regulation: Risks of exposure to cognitive enhancers vs other psychostimulants. The images or other third party material in this article are included in the article's Creative Commons licence, unless indicated otherwise in a credit line to the material. Magnetic Resonance Imaging (MRI) is a rapid, non-destructive and three-dimensional method that can be used to quantitate brain structures volumes. Google Scholar. & Boehm-Sturm, P. On the usage of brain atlases in neuroimaging research. a node caudoputamen (CP) in Fig. Takata, N. et al. Mouse Brain Atlas A unique multimodal atlas of the adult mouse brain, featuring anatomic and genomic data. The green histogram is for FAAdetailed (Fig. However, the volume occupied by these small nodes was negligible: 0.6% of the whole brain volume. Optogenetic astrocyte activation evokes BOLD fMRI response with oxygen consumption without neuronal activity modulation. (John Wiley & Sons Inc, 2008). Sign up for the Nature Briefing newsletter what matters in science, free to your inbox daily. Clifton NJ 711, 251270 (2011). Cembrowski, M. S. & Spruston, N. Heterogeneity within classical cell types is the rule: Lessons from hippocampal pyramidal neurons. Neurosci. Grandjean, J. et al. Colors of markers at the top show that FC from the ventral CA1 was significantly higher (blue) or lower (red) than FC from the dorsal CA1. By contrast, four nodes in the brain parenchyma were larger than 10,000 nL (dotted line in Fig. 3c bottom panels). The Allen Mouse Brain Atlas includes a full-color, high-resolution anatomic reference atlas accompanied by a systematic, hierarchically organized taxonomy of mouse brain structures. Takata, N., Sato, N., Komaki, Y. et al. Despite these excellent annotation atlases, it is still common in MRI studies of the mouse brain that ROIs for brain structures are prepared with arbitrary boundaries and locations according to each researchers necessities. 4c). http://help.brain-map.org/display/mousebrain/API (2014). (e) Histogram of correlation coefficients between leaf nodes (filled histogram), between a leaf node and an inner node (dotted line), and between inner nodes (solid line) in the FC matrix by FAAcoarse (red color). Astrocyte calcium signaling transforms cholinergic modulation to cortical plasticity in vivo. Resting-state fMRI was performed in awake mice using a CryoProbe, as described previously12,24,25. The absence of a de facto standard annotation atlas for the mouse brain in MRI studies might engender inconsistent ROI definitions for brain structures, making it difficult to compare, replicate, and validate results obtained from other laboratories19. 3-D digital mouse brain atlas was created to support and integrate multimodal data generated as part of this plan. Neuroimage 78, 196203 (2013). Get the most important science stories of the day, free in your inbox. Total ROI counts of FAA can vary from 1 to more than 1000. 3c right histogram) indicated the node as divisible into two: nodes with lower or higher gene expression CA1_geneL or CA1_geneH, respectively (blue and red areas in Fig. 13, 20 (2019). 4d). Instances of more numerous squares over dots suggest distinct patterns of FCs from the ventral and dorsal CA1. FAAcoarse realized FC analysis across the anatomical hierarchy because FAAcoarse retains hierarchy-related information. The width of each node represents its size. Color codes at the top and left represent brain structures. From preprocessing, destructive nodes in the original AO were eliminated, thereby creating a modified AO without destructive nodes, i.e. J. Neurosci. Arrowheads show divided leaf nodes based on fiber projection density in the left (CP_fiberL_L and CP_fiberH_L) and the right (CP_fiberL_R and CP_fiberH_R) side of the brain. Waxholm space: An image-based reference for coordinating mouse brain research. PubMed Central & Mori, S. Magnetic resonance imaging-based mouse brain atlas and its applications. This analysis assumed that BOLD-signal fluctuation was uniform within each cortical layer, and that contaminating signals in a node from other nodes were cancelled out by averaging signals within the target node. The Atlas of the Prenatal Mouse Brain is the latest addition to Academic Press' list of atlases for neuroscientists and neuroscience students. PubMed A publication on characterization of tau pathology in the locus coeruleus in the human brain using three-dimensional imaging was recently selected as recipient of a 2023 Publication of the Year Award by the Alzheimer's Association ISTAART. These AObase and AVbase were designated collectively as FAAbase, which had a total node count of 866, among which 197 and 669 were inner and leaf nodes, respectively. Hence, the plot clearly shows the relationship between volumes of child and parent nodes. 1c; see Fig. Neurosci. J. Neurophysiol. Neurobiol. 1c). 105, 27532763 (2011). 13, 809816 (2019). Spatial preprocessing of MRI data was performed using Advanced Normalization Tools (ANTs 2.1.0; http://stnava.github.io/ANTs/), Brain Extraction Tool (BET)29, and SPM12 (7487, Welcome Trust Centre for Neuroimaging, London, UK). Neuron 76, 629639 (2012). A root node at the top has child nodes, root_L and root_R, indicating that FAAcoarse is double-sided, i.e. leaf nodes islands of Calleja (isl) and olfactory tubercle, molecular layer (OT1) in Fig. The current study addressed this issue by constructing a pipeline for a flexible annotation atlas (FAA). Non-significant correlation coefficients in the FC matrix were set to 0. Data are expressed as meanstandard error of the mean (SEM) across animals, except where otherwise noted. Scroll down for more background on this atlas. Scheeringa, R. & Fries, P. Cortical layers, rhythms and BOLD signals. PubMed Nat. Neurosci. Pallast, N. et al. Click on a button to view the corresponding section, or use the numbered guide in the frame below. For example, a node root is a parent node of its child nodes grey and fiber tracts. Earlier studies have analyzed only FCs between leaf nodes, e.g. A standard brain atlas plays a key role in magnetic resonance imaging (MRI) for investigating anatomical and functional architecture of the brain1,2,3. Anyone you share the following link with will be able to read this content: Sorry, a shareable link is not currently available for this article. Nevertheless, FAA would be able to incorporate future development and re-defining of anatomical structures of the mouse brain by spatially registering them to the Allen Brain Atlas coordinates. Whereas leaf nodes in the PFC such as the prelimbic area (PL), infralimbic area (ILA), and orbital area (ORB) had high FC within these leaf nodes (dense red region pointed by arrows in Fig. After two earlier editions in 2008 and 2011, AIBS provided a complete version for a common coordinate framework ver. eLife 5, 20 (2016). Physiological effects of a habituation procedure for functional MRI in awake mice using a cryogenic radiofrequency probe. Especially strong FCs around 0.81.0 were observed between inner nodes CH and CTX and CTXpl and Isocortex. Fig. 1b right). By submitting a comment you agree to abide by our Terms and Community Guidelines. BOLD fMRI signals of an inner node were calculated as a size-weighted average of BOLD-fMRI signals in its descendant leaf nodes. 1b. For instance, combining leaf node islands of Calleja (isl) and olfactory tubercle, molecular layer (OT1) to prepare a new leaf node olfactory tubercle (OT) in the original AO does not accompany modification of the original AV (Fig. Statistical tests revealed, however, that FC from the source node to the inner node was not always significantly larger than FCs to the descendant leaf nodes. Marked variation of FC within cortical layers was observed in most cortical regions. PubMed Concretely, a node was divided to two using a threshold for (1) gene expression energy in the node that was defined as gene expression intensityexpression density of ISH image for a gene (Fig. Brain networks, dimensionality, and global signal averaging in resting-state fMRI: Hierarchical network structure results in low-dimensional spatiotemporal dynamics. Prog. Lower panels: divided nodes. Similarly, 29 inner nodes in the original AO have corresponding voxels in the AV. Methods 14, 112116 (2017). Johnson, G. A. et al. The node size reflects the strength of FC. Computer codes: N.T., N.S. Res. ISSN 2045-2322 (online). The Mouse Brain Library Mouse Brain Atlas: DBA/2J Horizontal Use the image below to select a section through the brain. EPFL. Rubinov, M., Ypma, R. J. F., Watson, C. & Bullmore, E. T. Wiring cost and topological participation of the mouse brain connectome. Whole-brain imaging study with tissue-clearing techniques or a serial-sectioning imaging system would benefit from consistent and flexible ROIs provided by FAA, once registered to the Allen reference atlas55,56,57,58. CCF Version 3 (v3) is based on a 3-D 10m isotropic, highly detailed . The proposed pipeline for FAA construction enables the combination of brain structures in AVbase while maintaining anatomical hierarchy in AObase (Fig. S1). Neuroimage 153, 382398 (2017). Ellipses and rectangles respectively denote the leaf node and inner node. Springer Nature remains neutral with regard to jurisdictional claims in published maps and institutional affiliations. Identification of the extent of cortical spreading depression propagation by Npas4 mRNA expression. 10, 5067 (2019). Use the Previous and Next buttons to navigate the slides or the slide controller buttons at the end to navigate through each slide. (b) Preprocessing of the original AO (left) for eliminating destructive nodes to obtain a modified AO (designated as AObase; right). Curr. Multimodal image registration and connectivity analysis for integration of connectomic data from microscopy to MRI. PLoSOne 14, e0212898 (2019). Watson, C. et al. different IDs are assigned to homotopic nodes in the left and right side of the brain. Cortex 15, 639645 (2005). Larger node size is evident in this AVcoarse than AVbase (Fig. Common functional networks in the mouse brain revealed by multi-centre resting-state fMRI analysis. Still, node for each cortical layer was 1325 times larger than a single voxel of fMRI (30 nL), except for layer 6b (77 nL). A brain atlas is necessary for analyzing structure and function in neuroimaging research. Specifically, there were 229 significant FCs from a node CA1_geneL (ventral CA1) and/or a node CA1_geneH (dorsal CA1) in the FC matrix (n=13, paired t tests with FDR adjusted p value of 0.05). Flexible annotation atlas of the mouse brain: combining and dividing brain structures of the Allen Brain Atlas while maintaining anatomical hierarchy. A three-dimensional digital atlas database of the adult C57BL/6J mouse brain by magnetic resonance microscopy. Nat. Red and green plots are for FAAcoarse and FAAdetailed (see Figs. CAS This procedure was left as manual rather than automated by program codes because simple criteria such as thresholding by node size turned out to be insufficient to achieve flexibility for combining nodes. Actually, AIBS provides several three-dimensional volume data for AT, AV, and axonal projection density with different spatial resolutions (10100m isovoxel; Supplementary Table 1). Nat. Among the leaf nodes, 31% (339 leaf nodes) passed the first criterion. 1a right). 37, 80928101 (2017). Goubran, M. et al. Ventral CP receives cortical afferents mainly from the insular cortex37,38. FC from a source leaf node S to leaf nodes (b,c). For a conventional diagram, see Brain Explorer 2 by AIBS (https://mouse.brain-map.org/static/brainexplorer). Allen Institute for Brain Science. Furthermore, modulation of FC by larger units in the brain, i.e. All maps have a isotropic voxel size . Every node has a unique parent node except the root. 2a). One reason for such a situation is the fact that earlier AVs were fixed, i.e. 9, 12 (2018). Nodes in the left and right side of the brain have, respectively, bluish and reddish colors reflecting that nodes in the right hemisphere were assigned larger IDs. Removal of confounding effects by linear regression was performed using (1) linear/quadratic trends within each functional run, (2) realignment-based subject motion, (3) noise signals in white matter and CSF, obtained with component-based noise correction method (CompCor), and (4) 0.010.1Hz band-pass filtering. Similar results were obtained for all source leaf nodes. Grandjean, J., Zerbi, V., Balsters, J. H., Wenderoth, N. & Rudin, M. Structural basis of large-scale functional connectivity in the mouse. 21, 139149 (2018). AV is shown in NIH color scheme, with each voxel assigned an integer value for an ID of a brain structure. The thresholds were defined objectively as an inflection point of fitted curves in histograms for gene expression energy or fiber projection density in a node (Fig. Neuroimage 199, 718729 (2019). 1b right). L denotes the left side of the brain. Proc. Shadows drawn on a map simulate the effects of sunlight falling across the surface . The superior colliculus, a conserved midbrain node with extensive long-range connectivity throughout the brain, is a key structure for innate behaviors. Diamonds show 13 pairs of an. 2e solid red line). 4d), i.e. Doucet, G. et al. Nat. MosquitoBrains.org Brain atlas for the female Aedes aegypti mosquito. 2e, solid and dotted lines). Inner nodes such as the cerebral cortex (CTX, pale green in color codes) and its descendant nodes typically had higher FC than leaf nodes. Such a new leaf node was assigned a new, unique ID and was given a structure name and acronym of an original inner node, suffixed respectively with _peripheral and _peri. 2a left) were combined to create a new leaf node somatosensory areas (SS) in AOcoarse (Fig. This situation conflicts with a recent trend for data-sharing in neuroscience41,42,43. ADS RSPv1_R (517 nL, 0.800.02), RSPv2/3_R (549 nL, 0.810.02), RSPv5_R (828 nL, 0.730.03), RSPv6a_R (326 nL, 0.480.04), and RSPv6b_R (21 nL, 0.390.04). The color code for the brain structure follows that of AIBS, and is applicable to Figs. To investigate the case, an FC matrix obtained with FAAdetailed was examined in a search for source leaf nodes S that met the following three criteria: (1) FC between S and an inner node A was larger than 0.8; (2) the inner node A was not an ancestor of the leaf node S, and (3) FC between them was larger than FC from node S to the leaf nodes (B and C) which were descendants of inner node A. FAAdetailed had 1363 grey-matter nodes, among which 277 were inner nodes and 1086 were leaf nodes. Biol. Natl. Magn. Neurobiol. Article 1b left). Waves at each node represent the resting-state activity (BOLD signal). The second of those five resources, AT, is a three-dimensional average volume of the mouse brain constructed with serial two-photon tomography using 1675 specimens. Nat. Matsubayashi, K. et al. 31, 1815518165 (2011). 3e,f). (b) An icicle plot of anatomical hierarchy of FAAcoarse. As an example of FC modulation across the hierarchy, one can presume a situation in which FC from a source leaf node S to an inner node A is higher than that to leaf node B or C, which are descendants of the inner node A (Fig. Resting-state FC across the anatomical hierarchy and between cortical layers. PubMedGoogle Scholar. Two-dimensional wide-field cortical imaging can also use FAA59,60,61,62 through a flat-map projection of the Allen reference atlas63,64. Specifically, the original AO was preprocessed to obtain AObase without destructive nodes, which means that leaf nodes and inner nodes in AObase do and do not have corresponding voxels in the original AV, respectively (Fig. Correspondence to Furthermore, 80.8% of the FCs (185 among 229 FCs) were significant only for either ventral or dorsal CA1, implying distinct patterns of FCs from those of ventral and dorsal CA1. The fMRI scanning covered the whole brain including the olfactory bulb and the cerebellum. A shift to the right of solid and dotted lines compared to a filled histogram confirms higher FCs for inner nodes. 3c upper panels), and (4) axonal fiber projection data (Fig. Seibt, J. et al. Consequently, FAAcoarse had a total node count of 101, among which 80 were leaf nodes. Publication 3-D imaging Immunofluorescence microscopy Neurodegenerative disorders. CNU, cerebral nuclei; STR, striatum; STRd and STRv, dorsal and ventral region of STR; OT, olfactory tubercle; isl, islands of Calleja; OT1, molecular layer of OT. Specifically, 6.7% of all leaf nodes in FAAbase were smaller than a single voxel in fMRI (30 nL, dashed line). Arrowheads indicate ancestor nodes for the PFC, i.e. Therefore, a more likely interpretation for higher FC between a source leaf node and an inner node observed here might be an SNR increase by averaging of BOLD-fMRI signals in descendant leaf nodes of the inner node. Access Online via Elsevier, 2001. Nodes for fiber traces and ventricular systems (VS) are included in FAAbase (indicated by the dashed arrow at the upper right). Neuroimage 157, 275287 (2017). This procedure of division modified AObase, which we designated as AOdetailed, and yielded its corresponding annotation volume, AVdetailed. 1a). Seiriki, K. et al. Sci. A node at the top of an anatomical hierarchy in AO is a root node defined as an ancestor of every node (Fig. A thresholding histogram of the gene-expression energy in a leaf node CA1 (Fig. A pair of AObase and AVbase was designated collectively as a flexible annotation atlas base (FAAbase). 2), and (2) dividing a leaf node of FAAbase using resources at AIBS on gene expression and axonal projection (Fig. The horizontal-vertical spread in Figure 6g is striking, giving a relative measurement of laminar versus areal gene expression in the brain. The pipeline for FAA construction enables classification of leaf nodes objectively using public resources by AIBS on gene expression and axonal projection. Gene expression database goes online. We intended to discard a whole run if confounding volumes exceeded 20% of all volumes, but this did not occur (3.00.9%, n=13 runs). Similarly, time-series fMRI images were processed: (1) the first four volumes were taken away as dummy scans corresponding to the first 6s of imaging (SPM file conversion); (2) images were realigned for head-motion correction (SPM-realign: Estimate & Reslice; Quality, 1; Separation, 3mm; Smoothing, 5mm; Register to mean; Interpolation with 2nd degree B-spline; Note that the scale dimension unit was10 of naive space. Ma, Y. et al. Sawiak, S. J., Wood, N. I., Williams, G. B., Morton, A. J. Finally, the mean denoised fMRI timeseries in each node was obtained by assigning FAAcoarse or FAAdetailed as an atlas file in CONN. Neuroimage 205, 116289 (2020). Google Scholar. cortical plate (CTXpl) and isocortex. Franklin. Analysis and interpretation of data: N.T. Richardson, D. S. & Lichtman, J. W. Clarifying tissue clearing. The markers above correspond to levels of the Atlas. Another caveat is discrepancy of anatomical labels of Allen Brain Atlas with that of the FranklinPaxinos atlas, the another most commonly used brain atlas54. Sizes of the largest four leaf nodes in the original AV exceed 10,000 nL (Fig. The final step (6) modulated spatial resolution of fMRI images to be 100m isovoxels, the same as the original volumes by AIBS. A double line rectangle shows a root node of a rooted tree graph. CAS an inner node might be able to constitute a larger unit to control the activities of its descendant leaf nodes. 20, 299303 (2017). Furthermore, only leaf nodes were examined as source nodes in this study. In vivo magnetic resonance images reveal neuroanatomical sex differences through the application of voxel-based morphometry in C57BL/6 mice. 3c or d, right). Methods Mol. These nodes still appear as light grey in a list at an Allen Institute web site, http://atlas.brain-map.org/atlas?atlas=1#atlas=1&structure=465&resolution=10.87&x=4560.044008725649&y=3727.8479489413176&zoom=-3&plate=100960348). 2c; see step 3-1 in Supplementary Table 4). An inner node is a node with at least one child node, e.g. Methods 17, 107113 (2020). Commun. 8, 684 (2017). Although various annotation volumes (AVs) for the mouse brain have been proposed, it is common in magnetic resonance imaging (MRI) of the mouse brain that regions-of-interest (ROIs) for brain structures (nodes) are created arbitrarily according to each researchers necessity, leading to inconsistent ROIs among studies. Functional connectivity with cortical depth assessed by resting state fMRI of subregions of S1 in squirrel monkeys. Neuroimage 42, 6069 (2008). & Svoboda, K. A large field of view two-photon mesoscope with subcellular resolution for in vivo imaging. Thank you for visiting nature.com. Hess, A., Hinz, R., Keliris, G. A.

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