Journal
PROCEEDINGS OF THE NATIONAL ACADEMY OF SCIENCES OF THE UNITED STATES OF AMERICA
Volume 117, Issue 8, Pages 4375-4384Publisher
NATL ACAD SCIENCES
DOI: 10.1073/pnas.1912176117
Keywords
single-cell RNA-seq; neural circuits; stress
Categories
Funding
- Millen Literary Trust
- Howard Hughes Medical Institute
- NIH [R01 DC015032, R01 DC016442, DP2 HD088158]
- Paul G. Allen Frontiers Foundation through the Allen Discovery Center for Cell Lineage Tracing
- Alfred P. Sloan Fellowship
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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.
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