title: New rabies virus variants for monitoring and manipulating activity and gene expression in defined neural circuits.
abstract: Glycoprotein-deleted (ΔG) rabies virus is a powerful tool for studies of neural circuit structure. Here, we describe the development and demonstrate the utility of new resources that allow experiments directly investigating relationships between the structure and function of neural circuits. New methods and reagents allowed efficient production of 12 novel ΔG rabies variants from plasmid DNA. These new rabies viruses express useful neuroscience tools, including the Ca(2+) indicator GCaMP3 for monitoring activity; Channelrhodopsin-2 for photoactivation; allatostatin receptor for inactivation by ligand application; and rtTA, ER(T2)CreER(T2), or FLPo, for control of gene expression. These new tools allow neurons targeted on the basis of their connectivity to have their function assayed or their activity or gene expression manipulated. Combining these tools with in vivo imaging and optogenetic methods and/or inducible gene expression in transgenic mice will facilitate experiments investigating neural circuit development, plasticity, and function that have not been possible with existing reagents.
authors.affiliation: Systems Neurobiology Laboratories, The Salk Institute for Biological Studies, La Jolla, CA 92037, USA.
authors.forename: Fumitaka
authors.initials: F
authors.lastname: Osakada
authors.forename: Takuma
authors.initials: T
authors.lastname: Mori
authors.forename: Ali H
authors.initials: AH
authors.lastname: Cetin
authors.forename: James H
authors.initials: JH
authors.lastname: Marshel
authors.forename: Beatriz
authors.initials: B
authors.lastname: Virgen
authors.forename: Edward M
authors.initials: EM
authors.lastname: Callaway
mesh_terms: D000200:Action Potentials / Q000187:drug effects / Q000502:physiology; D000818:Animals; D000956:Antigens, Viral / Q000235:genetics* / Q000378:metabolism*; D015870:Gene Expression; D014644:Genetic Variation; D005822:Genetic Vectors; D006023:Glycoproteins / Q000235:genetics* / Q000378:metabolism*; D006727:Hormone Antagonists / Q000494:pharmacology; D051379:Mice; D008822:Mice, Transgenic; D009415:Nerve Net / Q000033:anatomy & histology / Q000502:physiology*; D009474:Neurons / Q000187:drug effects / Q000502:physiology* / Q000821:virology; D009479:Neuropeptides / Q000494:pharmacology; D018408:Patch-Clamp Techniques; D011820:Rabies virus / Q000235:genetics* / Q000378:metabolism; D011993:Recombinant Fusion Proteins / Q000235:genetics / Q000378:metabolism; D014759:Viral Envelope Proteins / Q000235:genetics* / Q000378:metabolism*
chemical_list: D000956:Antigens, Viral; D006023:Glycoproteins; D006727:Hormone Antagonists; D009479:Neuropeptides; D011993:Recombinant Fusion Proteins; D014759:Viral Envelope Proteins; C064951:glycoprotein G, Rabies virus; C076523:allatostatin