The Allen Mouse Brain Common Coordinate Framework: A 3D Reference Atlas.

Recent large-scale collaborations are generating major surveys of cell types and connections in the mouse brain, collecting large amounts of data across modalities, spatial scales, and brain areas. Successful integration of these data requires a standard 3D reference atlas. Here, we present the Allen Mouse Brain Common Coordinate Framework (CCFv3) as such a resource. We constructed an average template brain at 10 µm voxel resolution by interpolating high resolution in-plane serial two-photon tomography images with 100 µm z-sampling from 1,675 young adult C57BL/6J mice. Then, using multimodal reference data, we parcellated the entire brain directly in 3D, labeling every voxel with a brain structure spanning 43 isocortical areas and their layers, 329 subcortical gray matter structures, 81 fiber tracts, and 8 ventricular structures. CCFv3 can be used to analyze, visualize, and integrate multimodal and multiscale datasets in 3D and is openly accessible (https://atlas.brain-map.org/).

Organization of the connections between claustrum and cortex in the mouse.

The connections between the claustrum and the cortex in mouse are systematically investigated with adeno-associated virus (AAV), an anterograde viral tracer. We first define the boundary and the three-dimensional structure of the claustrum based on a variety of molecular and anatomical data. From AAV injections into 42 neocortical and allocortical areas, we conclude that most cortical areas send bilateral projections to the claustrum, the majority being denser on the ipsilateral side. This includes prelimbic, infralimbic, medial, ventrolateral and lateral orbital, ventral retrosplenial, dorsal and posterior agranular insular, visceral, temporal association, dorsal and ventral auditory, ectorhinal, perirhinal, lateral entorhinal, and anteromedial, posteromedial, lateroposterior, laterointermediate, and postrhinal visual areas. In contrast, the cingulate and the secondary motor areas send denser projections to the contralateral claustrum than to the ipsilateral one. The gustatory, primary auditory, primary visual, rostrolateral visual, and medial entorhinal cortices send projections only to the ipsilateral claustrum. Primary motor, primary somatosensory and subicular areas barely send projections to either ipsi- or contralateral claustrum. Corticoclaustral projections are organized in a rough topographic manner, with variable projection strengths. We find that the claustrum, in turn, sends widespread projections preferentially to ipsilateral cortical areas with different projection strengths and laminar distribution patterns and to certain contralateral cortical areas. Our quantitative results show that the claustrum has strong reciprocal and bilateral connections with prefrontal and cingulate areas as well as strong reciprocal connections with the ipsilateral temporal and retrohippocampal areas, suggesting that it may play a crucial role in a variety of cognitive processes. J. Comp. Neurol. 525:1317-1346, 2017. © 2016 Wiley Periodicals, Inc.

Expression profiling of the solute carrier gene family in the mouse brain.

The solute carrier (Slc) superfamily is a major group of membrane transport proteins present in mammalian cells. Although Slc transporters play essential and diverse roles in the central nervous system, the localization and function of the vast majority of Slc genes in the mammalian brain are largely unknown. Using high-throughput in situ hybridization data generated by the Allen Brain Atlas, we systematically and quantitatively analyzed the spatial and cellular distribution of 307 Slc genes, which represent nearly 90% of presently known mouse Slc genes, in the adult C57BL/6J mouse brain. Our analysis showed that 252 (82%) of the 307 Slc genes are present in the brain, and a large proportion of these genes were detected at low to moderate expression levels. Evaluation of 20 anatomical brain subdivisions demonstrated a comparable level of Slc gene complexity but significant difference in transcript enrichment. The distribution of the expressed Slc genes was diverse, ranging from near-ubiquitous to highly localized. Functional annotation in 20 brain regions, including the blood-brain and blood-cerebral spinal fluid (CSF) barriers, suggests major roles of Slc transporters in supporting brain energy utilization, neurotransmission, nutrient supply, and CSF production. Furthermore, hierarchical cluster analysis revealed intricate Slc expression patterns associated with neuroanatomical organization. Our studies also revealed Slc genes present within defined brain microstructures and described the putative cell types expressing individual Slc genes. These results provide a useful resource for investigators to explore the roles of Slc genes in neurophysiological and pathological processes.