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Transcriptomic-anatomic analysis of the mouse habenula uncovers a high molecular heterogeneity among neurons in the lateral complex, while gene expression in the medial complex largely obeys subnuclear boundaries

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Abstract

The mammalian habenula with its medial and lateral complexes has gained much interest in recent years, while knowledge on the detailed biological functions of these nuclei is still scarce. Novel strategies to differentiate and identify habenular cell types are required. Such attempts have largely failed, most likely due to the lack of appropriate molecular markers. One important tool to approach this dilemma is available in form of the Allen Brain Atlas (ABA), which provides detailed expression patterns of many genes in the mouse brain. In the present report, ABA tools in combination with visual inspection of ISH images were used to detect transcripts, which are strongly expressed in medial (MHb) and lateral (LHb) habenular complexes. Against our expectations, most transcripts were differentially distributed throughout the LHb, disregarding boundaries of subnuclear areas. Nine distinct distribution patterns were recognized. Yet, several transcripts could not be attributed to one of these, suggesting a high diversity of neuron types in the LHb. In the MHb, in contrast, many transcripts tended to obey subnuclear boundaries. The differential distribution of others like Adcyap1, Chrna3, or Trp53i11 suggests the presence of a novel subfield adjacent to the region of the MHbVm, which now is termed intermediate field of the ventral MHb. In addition, the localizations of Amigo2, Adcyap1, and a couple of other transcripts suggest a lateral extension of the MHb, which is here, termed HbX area. Apparently, this area is composed of intermingled MHb and LHb neurons and may allow functional interaction between the both habenular complexes.

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  1. Institut für Zell- und Neurobiologie, Centrum 2, Charité-Universitätsmedizin Berlin, Philippstrasse 12, D-10115, Berlin, Germany

    Franziska Wagner & Rüdiger W. Veh

  2. Rotman Research Institute, University of Toronto, 3560 Bathurst Street, Toronto, M6A 2E1, Canada

    Leon French

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  1. Franziska Wagner
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Correspondence to Rüdiger W. Veh.

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This report contains part of the doctoral thesis (MD) of F. Wagner.

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429_2014_891_MOESM1_ESM.xls

Table 1 (Supplement): Complete list of the 138 transcripts, which were analyzed with respect to their detailed distributions within the LHb. Captation figures schematically display the corresponding patterns. Areas with high cell densities are shown in dark blue, those with low densities in light blue, and the HBX field in yellow (XLS 409 kb)

429_2014_891_MOESM2_ESM.xls

Table 2 (Supplement): Complete list of genes with characteristic expressions in the MHb. Captation figures schematically display the corresponding localizations. Selected subnuclei are shown in dark blue, others in light blue, the border zone in orange, and the HBX field in yellow (XLS 391 kb)

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Wagner, F., French, L. & Veh, R.W. Transcriptomic-anatomic analysis of the mouse habenula uncovers a high molecular heterogeneity among neurons in the lateral complex, while gene expression in the medial complex largely obeys subnuclear boundaries. Brain Struct Funct 221, 39–58 (2016). https://doi.org/10.1007/s00429-014-0891-9

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