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A transcriptomic taxonomy of mouse brain-wide spinal projecting neurons.

ABSTRACT: The brain controls nearly all bodily functions via spinal projecting neurons (SPNs) that carry command signals from the brain to the spinal cord. However, a comprehensive molecular characterization of brain-wide SPNs is still lacking. Here we transcriptionally profiled a total of 65,002 SPNs, identified 76 region-specific SPN types, and mapped these types into a companion atlas of the whole mouse brain¹. This taxonomy reveals a three-component organization of SPNs: (1) molecularly homogeneous excitatory SPNs from the cortex, red nucleus and cerebellum with somatotopic spinal terminations suitable for point-to-point communication; (2) heterogeneous populations in the reticular formation with broad spinal termination patterns, suitable for relaying commands related to the activities of the entire spinal cord; and (3) modulatory neurons expressing slow-acting neurotransmitters and/or neuropeptides in the hypothalamus, midbrain and reticular formation for 'gain setting' of brain-spinal signals. In addition, this atlas revealed a LIM homeobox transcription factor code that parcellates the reticulospinal neurons into five molecularly distinct and spatially segregated populations. Finally, we found transcriptional signatures of a subset of SPNs with large soma size and correlated these with fast-firing electrophysiological properties. Together, this study establishes a comprehensive taxonomy of brain-wide SPNs and provides insight into the functional organization of SPNs in mediating brain control of bodily functions.

SUBMITTER: Winter CC

PROVIDER: S-EPMC10719099 | biostudies-literature | 2023 Dec

REPOSITORIES: biostudies-literature

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A transcriptomic taxonomy of mouse brain-wide spinal projecting neurons.

Winter Carla C CC Jacobi Anne A Su Junfeng J Chung Leeyup L van Velthoven Cindy T J CTJ Yao Zizhen Z Lee Changkyu C Zhang Zicong Z Yu Shuguang S Gao Kun K Duque Salazar Geraldine G Kegeles Evgenii E Zhang Yu Y Tomihiro Makenzie C MC Zhang Yiming Y Yang Zhiyun Z Zhu Junjie J Tang Jing J Song Xuan X Donahue Ryan J RJ Wang Qing Q McMillen Delissa D Kunst Michael M Wang Ning N Smith Kimberly A KA Romero Gabriel E GE Frank Michelle M MM Krol Alexandra A Kawaguchi Riki R Geschwind Daniel H DH Feng Guoping G Goodrich Lisa V LV Liu Yuanyuan Y Tasic Bosiljka B Zeng Hongkui H He Zhigang Z

Nature 20231213 7991

The brain controls nearly all bodily functions via spinal projecting neurons (SPNs) that carry command signals from the brain to the spinal cord. However, a comprehensive molecular characterization of brain-wide SPNs is still lacking. Here we transcriptionally profiled a total of 65,002 SPNs, identified 76 region-specific SPN types, and mapped these types into a companion atlas of the whole mouse brain<sup>1</sup>. This taxonomy reveals a three-component organization of SPNs: (1) molecularly hom ...[more]

PMID: 38092914

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Project description:The brain executes control of nearly all bodily functions via spinal projecting neurons (SPNs) that carry command signals from numerous supraspinal regions to the spinal cord. Despite their physiological and clinical relevance, a comprehensive molecular characterization of SPNs is still lacking. Here, we use retrograde labeling, whole-brain imaging, and high-throughput transcriptional profiling to generate a unified brain-wide anatomic and transcriptomic atlas of adult mouse SPNs at single-cell resolution. We transcriptionally profiled a total of 65,002 SPNs, identified 76 region-specific SPN types, and mapped these types into a companion atlas of the whole mouse brain generated by the Allen Institute for Brain Science within the BRAIN Initiative Cell Census Network (BICCN). This SPN taxonomy reveals a three-component organization of SPNs: (1) molecularly homogeneous excitatory SPNs from the cortex, red nucleus, and cerebellum with somatotopic spinal terminations suitable for point-to-point communication; (2) highly heterogeneous excitatory and inhibitory populations in the reticular formation with broad spinal termination patterns, thus suitable for relaying commands related to the activities of the entire spinal cord; and (3) modulatory neurons expressing slow-acting neurotransmitters and/or neuropeptides in the hypothalamus, midbrain, and reticular formation for gain control of brain-spinal signals. Within each of these components, this atlas revealed additional insights. From components (2) and (3), we discovered a LIM homeobox transcription factor code that parcellates the most transcriptionally complex population, reticulospinal neurons, into five molecularly distinct and spatially segregated populations. For neurons in component (1), we found transcriptional signatures of a subset of SPNs with large soma size and correlated these with fast-firing electrophysiological properties; thus, at least two different cable lines (namely, Pvalb/Kcng4/Spp1 positive and negative) with different electrophysiological properties might underlie the transmission of brain signals to the spinal cord. Together, by integrating the anatomy, molecular identity, and physiological properties, this study establishes a comprehensive taxonomy of brain-wide SPNs and provides insight into the functional organization of SPNs in mediating brain control of bodily functions.

Dataset Information

A transcriptomic taxonomy of mouse brain-wide spinal projecting neurons.

Publications

A transcriptomic taxonomy of mouse brain-wide spinal projecting neurons.

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