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3 Publications

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    Dudman LabSternson LabSpruston LabSvoboda LabMouseLight
    09/19/19 | Reconstruction of 1,000 projection neurons reveals new cell types and organization of long-range connectivity in the mouse brain.
    Winnubst J, Bas E, Ferreira TA, Wu Z, Economo MN, Edson P, Arthur BJ, Bruns C, Rokicki K, Schauder D, Olbris DJ, Murphy SD, Ackerman DG, Arshadi C, Baldwin P, Blake R, Elsayed A, Hasan M, Ramirez D, Dos Santos B, Weldon M, Zafar A, Dudman JT, Gerfen CR, Hantman AW, Korff W, Sternson SM, Spruston N, Svoboda K, Chandrashekar J
    Cell. 2019 Sep 19;179(1):268-81. doi: 10.1016/j.cell.2019.07.042

    Neuronal cell types are the nodes of neural circuits that determine the flow of information within the brain. Neuronal morphology, especially the shape of the axonal arbor, provides an essential descriptor of cell type and reveals how individual neurons route their output across the brain. Despite the importance of morphology, few projection neurons in the mouse brain have been reconstructed in their entirety. Here we present a robust and efficient platform for imaging and reconstructing complete neuronal morphologies, including axonal arbors that span substantial portions of the brain. We used this platform to reconstruct more than 1,000 projection neurons in the motor cortex, thalamus, subiculum, and hypothalamus. Together, the reconstructed neurons constitute more than 85 meters of axonal length and are available in a searchable online database. Axonal shapes revealed previously unknown subtypes of projection neurons and suggest organizational principles of long-range connectivity.

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    04/12/19 | Mapping the transcriptional diversity of genetically and anatomically defined cell populations in the mouse brain.
    Sugino K, Clark E, Schulmann A, Shima Y, Wang L, Hunt DL, Hooks BM, Traenkner D, Chandrashekar J, Picard S, Lemire AL, Spruston N, Hantman AW, Nelson SB
    Elife. 2019 Apr 12;8:. doi: 10.7554/eLife.38619

    Understanding the principles governing neuronal diversity is a fundamental goal for neuroscience. Here we provide an anatomical and transcriptomic database of nearly 200 genetically identified cell populations. By separately analyzing the robustness and pattern of expression differences across these cell populations, we identify two gene classes contributing distinctly to neuronal diversity. Short homeobox transcription factors distinguish neuronal populations combinatorially, and exhibit extremely low transcriptional noise, enabling highly robust expression differences. Long neuronal effector genes, such as channels and cell adhesion molecules, contribute disproportionately to neuronal diversity, based on their patterns rather than robustness of expression differences. By linking transcriptional identity to genetic strains and anatomical atlases we provide an extensive resource for further investigation of mouse neuronal cell types.

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    04/10/18 | Dissociable structural and functional hippocampal outputs via distinct subiculum cell classes.
    Cembrowski MS, Phillips MG, DiLisio SF, Shields BC, Winnubst J, Chandrashekar J, Bas E, Spruston N
    Cell. 2018 Apr 10;173(5):1280-92. doi: 10.1016/j.cell.2018.03.031

    The mammalian hippocampus, comprised of serially connected subfields, participates in diverse behavioral and cognitive functions. It has been postulated that parallel circuitry embedded within hippocampal subfields may underlie such functional diversity. We sought to identify, delineate, and manipulate this putatively parallel architecture in the dorsal subiculum, the primary output subfield of the dorsal hippocampus. Population and single-cell RNA-seq revealed that the subiculum can be divided into two spatially adjacent subregions associated with prominent differences in pyramidal cell gene expression. Pyramidal cells occupying these two regions differed in their long-range inputs, local wiring, projection targets, and electrophysiological properties. Leveraging gene-expression differences across these regions, we use genetically restricted neuronal silencing to show that these regions differentially contribute to spatial working memory. This work provides a coherent molecular-, cellular-, circuit-, and behavioral-level demonstration that the hippocampus embeds structurally and functionally dissociable streams within its serial architecture.

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