title: Neuronal transgene expression in dominant-negative SNARE mice.
abstract: Experimental advances in the study of neuroglia signaling have been greatly accelerated by the generation of transgenic mouse models. In particular, an elegant manipulation that interferes with astrocyte vesicular release of gliotransmitters via overexpression of a dominant-negative domain of vesicular SNARE (dnSNARE) has led to documented astrocytic involvement in processes that were traditionally considered strictly neuronal, including the sleep-wake cycle, LTP, cognition, cortical slow waves, depression, and pain. A key premise leading to these conclusions was that expression of the dnSNARE was specific to astrocytes. Inconsistent with this premise, we report here widespread expression of the dnSNARE transgene in cortical neurons. We further demonstrate that the activity of cortical neurons is reversibly suppressed in dnSNARE mice. These findings highlight the need for independent validation of astrocytic functions identified in dnSNARE mice and thus question critical evidence that astrocytes contribute to neurotransmission through SNARE-dependent vesicular release of gliotransmitters.
authors.affiliation: Center for Translational Neuromedicine, University of Rochester Medical School, Rochester, New York 14642 nedergaard@urmc.rochester.edu Takumi_Fujita@urmc.rochester.edu.
authors.forename: Takumi
authors.initials: T
authors.lastname: Fujita
authors.affiliation: Center for Translational Neuromedicine, University of Rochester Medical School, Rochester, New York 14642.
authors.forename: Michael J
authors.initials: MJ
authors.lastname: Chen
authors.affiliation: Center for Translational Neuromedicine, University of Rochester Medical School, Rochester, New York 14642.
authors.forename: Baoman
authors.identifier: http://orcid.org/0000-0001-5758-4383
authors.initials: B
authors.lastname: Li
authors.affiliation: Center for Translational Neuromedicine, University of Rochester Medical School, Rochester, New York 14642.
authors.forename: Nathan A
authors.identifier: http://orcid.org/0000-0002-9254-5360
authors.initials: NA
authors.lastname: Smith
authors.affiliation: Center for Translational Neuromedicine, University of Rochester Medical School, Rochester, New York 14642.
authors.forename: Weiguo
authors.initials: W
authors.lastname: Peng
authors.affiliation: Center for Translational Neuromedicine, University of Rochester Medical School, Rochester, New York 14642.
authors.forename: Wei
authors.initials: W
authors.lastname: Sun
authors.affiliation: Center for Translational Neuromedicine, University of Rochester Medical School, Rochester, New York 14642.
authors.forename: Michael J
authors.initials: MJ
authors.lastname: Toner
authors.affiliation: Center for Translational Neuromedicine, University of Rochester Medical School, Rochester, New York 14642.
authors.forename: Benjamin T
authors.initials: BT
authors.lastname: Kress
authors.affiliation: Center for Translational Neuromedicine, University of Rochester Medical School, Rochester, New York 14642.
authors.forename: Linhui
authors.identifier: http://orcid.org/0000-0001-5295-324X
authors.initials: L
authors.lastname: Wang
authors.affiliation: Center for Translational Neuromedicine, University of Rochester Medical School, Rochester, New York 14642.
authors.forename: Abdellatif
authors.initials: A
authors.lastname: Benraiss
authors.affiliation: Center for Translational Neuromedicine, University of Rochester Medical School, Rochester, New York 14642.
authors.forename: Takahiro
authors.initials: T
authors.lastname: Takano
authors.affiliation: Center for Translational Neuromedicine, University of Rochester Medical School, Rochester, New York 14642.
authors.forename: Su
authors.initials: S
authors.lastname: Wang
authors.affiliation: Center for Translational Neuromedicine, University of Rochester Medical School, Rochester, New York 14642 nedergaard@urmc.rochester.edu Takumi_Fujita@urmc.rochester.edu.
authors.forename: Maiken
authors.initials: M
authors.lastname: Nedergaard
mesh_terms: D000818:Animals; D000831:Animals, Newborn; D002478:Cells, Cultured; D004569:Electroencephalography / Q000379:methods; D005260:Female; D005786:Gene Expression Regulation; D008297:Male; D051379:Mice; D008810:Mice, Inbred C57BL; D008822:Mice, Transgenic; D009474:Neurons / Q000378:metabolism*; D050600:SNARE Proteins / Q000096:biosynthesis* / Q000235:genetics; D012894:Sleep Stages / Q000502:physiology
chemical_list: D050600:SNARE Proteins
keywords: EEG; GFAP; SNARE; adenosine; sleep