Here we report the generation of a multimodal cell census and atlas of the mammalian primary motor cortex as the initial product of the BRAIN Initiative Cell Census Network (BICCN). This was achieved by coordinated large-scale analyses of single-cell transcriptomes, chromatin accessibility, DNA methylomes, spatially resolved single-cell transcriptomes, morphological and electrophysiological properties and cellular resolution input–output mapping, integrated through cross-modal computational analysis. Our results advance the collective knowledge and understanding of brain cell-type organization1–5. First, our study reveals a unified molecular genetic landscape of cortical cell types that integrates their transcriptome, open chromatin and DNA methylation maps. Second, cross-species analysis achieves a consensus taxonomy of transcriptomic types and their hierarchical organization that is conserved from mouse to marmoset and human. Third, in situ single-cell transcriptomics provides a spatially resolved cell-type atlas of the motor cortex. Fourth, cross-modal analysis provides compelling evidence for the transcriptomic, epigenomic and gene regulatory basis of neuronal phenotypes such as their physiological and anatomical properties, demonstrating the biological validity and genomic underpinning of neuron types. We further present an extensive genetic toolset for targeting glutamatergic neuron types towards linking their molecular and developmental identity to their circuit function. Together, our results establish a unifying and mechanistic framework of neuronal cell-type organization that integrates multi-layered molecular genetic and spatial information with multi-faceted phenotypic properties.

Neurodata Without Borders: Neurophysiology (NWB:N) is a data standard for neurophysiology, providing neuroscientists with a common standard to share, archive, use, and build common analysis tools for neurophysiology data. With NWB:N version 2.0 (NWB:N 2.0) we made significant advances towards creating a usable standard, software ecosystem, and vibrant community for standardizing neurophysiology data. In this manuscript we focus in particular on the NWB:N data standard schema and present advances towards creating an accessible data standard for neurophysiology. IntroductionMotivation: Brain function is produced by the coordinated activity of multiple neuronal types that are widely distributed across many brain regions. Neuronal signals are acquired using extra-and intracellular recordings, and increasingly optical imaging, during sensory, motor, and cognitive tasks. Neurophysiology research generates large, complex and heterogeneous datasets at terabyte scale. The data size and complexity is expected to continue to grow with the increasing sophistication of experimental apparatuses. Lack of standards for neurophysiology data and related metadata is the single greatest impediment to fully extracting return-on-investment from neurophysiology experiments, impeding interchange and reuse of data and reproduction of derived conclusions. This gap motivated the launch of the Neurodata Without Borders : Neurophysiology (NWB:N) data standards project. The goal of NWB:N is to develop a standardized format and methods for neurophysiology data and metadata.Background: The first NWB:N 1.0.x standard was the result of a 1 year pilot project in 2015 12 . As part of this pilot, neurophysiologists and software developers met during two hackathons to create a common data format for recordings and metadata of cellular electro-and optical physiology experiments (Fig. 1, top). Despite the important advances that NWB:N 1.0 made towards creating a neurophysiology data standard, the standard was not easily accessible to users. To enhance broad adoption, a sustainable software and community strategy and easy-to-use, high-level application programming interfaces (APIs) were desperately needed. Here we describe NWB:N 2.0, a modern ecosystem for data standardization and accessible data standard for neurophysiology.A Brief History of NWB:N 2.0: The development of the second version of NWB:N began in Janurary 2017 with the start of the Kavli funded NWB4HPC project. The goal was to develop infrastructure and algorithms to enable data-driven discovery and dissemination on high-performance computing systems for the BRAIN Initiative (Fig. 1, bottom). One main goal of the project was to develop the next version of NWB:N to enhance its adoption, with an initial focus on high-level APIs for read, write, and extension of the original NWB:N 1.0.x standard. This standard represented a critical first step toward a unified framework for neural data, but it became clear that in order to achieve these goals we needed an advanced software architecture, a well...

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Rhesus macaques are commonly used as a translational animal model in neuroimaging and neurodevelopmental research. In this report, we present longitudinal data from both structural and diffusion MRI images generated on a cohort of 34 typically developing monkeys from 2 weeks to 36 months of age. All images have been manually skull stripped and are being made freely available via an online repository for use by the research community.

Purinergic signalling plays a major role in intercellular communication between neurons and glial cells. Glial cells express metabotropic receptors for ATP and adenosine, the latter being activated after ATP cleavage through extracellular ecto-ATPase activity. Ionotropic receptors for extracellular ATP, so called P2X receptors, might contribute to neuron-glia signalling. However, experimental evidence for the presence of these receptors in glial cells is less convincing so far. In a previous study, immunohistochemistry was used to identify P2X(1-4,6,7) receptor protein in S100beta-positive hippocampal glial cells. Applying patch clamp and fast application techniques, here we challenged the question of the functional expression of these receptors. Time correlated membrane currents served as test criterion for receptor function, since P2X receptor activation leads to the opening of unspecific cation channels in a millisecond time scale. Agonists were applied via short pressure puffs, with a fast concentration clamp method and through UV flash triggered photolysis of caged ATP. Two types of murine hippocampal macroglial cells, both labelled by the expression of green fluorescence protein driven by the human glial fibrillary acid protein promoter, were analysed in acute brain slices and in freshly dissociated cell suspensions. Surprisingly, ATP or related agonists completely failed to activate currents. Additionally, changes in spontaneously occurring glial postsynaptic currents were never observed. These results have been verified using rat and human hippocampal tissue as well as investigating cells from P2X7 knock out mice. It is concluded that in acute preparations, astroglial cells of the hippocampal CA1 subfield do not express functional P2X receptors.