Connect-seq to superimpose molecular on anatomical neural circuit maps

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  • Naresh K. Hanchate
    Basic Sciences Division, Fred Hutchinson Cancer Research Center, Seattle, WA 98109;
  • Donghui Kuang
    Basic Sciences Division, Fred Hutchinson Cancer Research Center, Seattle, WA 98109;
  • Eun Jeong Lee
    Basic Sciences Division, Fred Hutchinson Cancer Research Center, Seattle, WA 98109;
  • Ryan Basom
    Genomics and Bioinformatics Shared Resource, Fred Hutchinson Cancer Research Center, Seattle, WA 98109;
  • Cole Trapnell
    Department of Genome Sciences, University of Washington, Seattle, WA 98115;
  • Kunio Kondoh
    Basic Sciences Division, Fred Hutchinson Cancer Research Center, Seattle, WA 98109;
  • Andria Ellis
    Department of Genome Sciences, University of Washington, Seattle, WA 98115;
  • Linda B. Buck
    Basic Sciences Division, Fred Hutchinson Cancer Research Center, Seattle, WA 98109;

Bibliographic Information

Published
2020-02-07
Resource Type
journal article
Rights Information
  • https://www.pnas.org/site/aboutpnas/licenses.xhtml
DOI
  • 10.1073/pnas.1912176117
  • 10.1101/454835
Publisher
Proceedings of the National Academy of Sciences

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<jats:p>The mouse brain contains about 75 million neurons interconnected in a vast array of neural circuits. The identities and functions of individual neuronal components of most circuits are undefined. Here we describe a method, termed “Connect-seq,” which combines retrograde viral tracing and single-cell transcriptomics to uncover the molecular identities of upstream neurons in a specific circuit and the signaling molecules they use to communicate. Connect-seq can generate a molecular map that can be superimposed on a neuroanatomical map to permit molecular and genetic interrogation of how the neuronal components of a circuit control its function. Application of this method to hypothalamic neurons controlling physiological responses to fear and stress reveals subsets of upstream neurons that express diverse constellations of signaling molecules and can be distinguished by their anatomical locations.</jats:p>

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