title: Capturing and Manipulating Activated Neuronal Ensembles with CANE Delineates a Hypothalamic Social-Fear Circuit.
abstract: We developed a technology (capturing activated neuronal ensembles [CANE]) to label, manipulate, and transsynaptically trace neural circuits that are transiently activated in behavioral contexts with high efficiency and temporal precision. CANE consists of a knockin mouse and engineered viruses designed to specifically infect activated neurons. Using CANE, we selectively labeled neurons that were activated by either fearful or aggressive social encounters in a hypothalamic subnucleus previously known as a locus for aggression, and discovered that social-fear and aggression neurons are intermixed but largely distinct. Optogenetic stimulation of CANE-captured social-fear neurons (SFNs) is sufficient to evoke fear-like behaviors in normal social contexts, whereas silencing SFNs resulted in reduced social avoidance. CANE-based mapping of axonal projections and presynaptic inputs to SFNs further revealed a highly distributed and recurrent neural network. CANE is a broadly applicable technology for dissecting causality and connectivity of spatially intermingled but functionally distinct ensembles.
authors.affiliation: Department of Neurobiology, Duke University Medical Center, Durham, NC 27710, USA.
authors.forename: Katsuyasu
authors.initials: K
authors.lastname: Sakurai
authors.affiliation: Department of Neurobiology, Duke University Medical Center, Durham, NC 27710, USA.
authors.forename: Shengli
authors.initials: S
authors.lastname: Zhao
authors.affiliation: Department of Neurobiology, Duke University Medical Center, Durham, NC 27710, USA.
authors.forename: Jun
authors.initials: J
authors.lastname: Takatoh
authors.affiliation: Department of Neurobiology, Duke University Medical Center, Durham, NC 27710, USA.
authors.forename: Erica
authors.initials: E
authors.lastname: Rodriguez
authors.affiliation: Department of Neurobiology, Duke University Medical Center, Durham, NC 27710, USA.
authors.forename: Jinghao
authors.initials: J
authors.lastname: Lu
authors.affiliation: Department of Laboratory Medicine, UCSF, San Francisco, CA 94143, USA.
authors.forename: Andrew D
authors.initials: AD
authors.lastname: Leavitt
authors.affiliation: Department of Neurobiology, Duke University Medical Center, Durham, NC 27710, USA.
authors.forename: Min
authors.initials: M
authors.lastname: Fu
authors.affiliation: Department of Neurobiology, Duke University Medical Center, Durham, NC 27710, USA.
authors.forename: Bao-Xia
authors.initials: BX
authors.lastname: Han
authors.affiliation: Department of Neurobiology, Duke University Medical Center, Durham, NC 27710, USA. Electronic address: fan.wang@duke.edu.
authors.forename: Fan
authors.initials: F
authors.lastname: Wang
mesh_terms: D000374:Aggression; D000818:Animals; D001369:Axons / Q000378:metabolism / Q000502:physiology; D001522:Behavior, Animal / Q000502:physiology*; D005239:Fear / Q000502:physiology*; D055879:Gene Knock-In Techniques; D007031:Hypothalamus / Q000166:cytology* / Q000378:metabolism / Q000502:physiology; D051379:Mice; D009415:Nerve Net / Q000378:metabolism / Q000502:physiology*; D009474:Neurons / Q000378:metabolism / Q000502:physiology*; D062308:Optogenetics; D016760:Proto-Oncogene Proteins c-fos / Q000378:metabolism; D012919:Social Behavior; D014697:Ventromedial Hypothalamic Nucleus / Q000166:cytology / Q000378:metabolism / Q000502:physiology
chemical_list: D016760:Proto-Oncogene Proteins c-fos
keywords: CANE; Fos; VMHvl; activity dependent; aggression; functional neural circuit; hypothalamus; social fear