title: Increased hippocampal excitability and impaired spatial memory function in mice lacking VGLUT2 selectively in neurons defined by tyrosine hydroxylase promoter activity.
abstract: Three populations of neurons expressing the vesicular glutamate transporter 2 (Vglut2) were recently described in the A10 area of the mouse midbrain, of which two populations were shown to express the gene encoding, the rate-limiting enzyme for catecholamine synthesis, tyrosine hydroxylase (TH).One of these populations ("TH-Vglut2 Class1") also expressed the dopamine transporter (DAT) gene while one did not ("TH-Vglut2 Class2"), and the remaining population did not express TH at all ("Vglut2-only"). TH is known to be expressed by a promoter which shows two phases of activation, a transient one early during embryonal development, and a later one which gives rise to stable endogenous expression of the TH gene. The transient phase is, however, not specific to catecholaminergic neurons, a feature taken to advantage here as it enabled Vglut2 gene targeting within all three A10 populations expressing this gene, thus creating a new conditional knockout. These knockout mice showed impairment in spatial memory function. Electrophysiological analyses revealed a profound alteration of oscillatory activity in the CA3 region of the hippocampus. In addition to identifying a novel role for Vglut2 in hippocampus function, this study points to the need for improved genetic tools for targeting of the diversity of subpopulations of the A10 area.
authors.affiliation: Unit of Functional Neurobiology and Unit of Developmental Genetics, Biomedical Center, Department of Neuroscience, Uppsala University, Box 593, S-751 24, Uppsala, Sweden.
authors.forename: Karin
authors.initials: K
authors.lastname: Nordenankar
authors.forename: Casey J A
authors.initials: CJ
authors.lastname: Smith-Anttila
authors.forename: Nadine
authors.initials: N
authors.lastname: Schweizer
authors.forename: Thomas
authors.initials: T
authors.lastname: Viereckel
authors.forename: Carolina
authors.initials: C
authors.lastname: Birgner
authors.forename: Jana
authors.initials: J
authors.lastname: Mejia-Toiber
authors.forename: Marisela
authors.initials: M
authors.lastname: Morales
authors.forename: Richardson N
authors.initials: RN
authors.lastname: Leao
authors.forename: Åsa
authors.initials: Å
authors.lastname: Wallén-Mackenzie
mesh_terms: D015102:3,4-Dihydroxyphenylacetic Acid / Q000378:metabolism; D000818:Animals; D002851:Chromatography, High Pressure Liquid; D004298:Dopamine / Q000378:metabolism; D004563:Electrochemistry; D005786:Gene Expression Regulation / Q000235:genetics; D049452:Green Fluorescent Proteins / Q000235:genetics / Q000378:metabolism; D006624:Hippocampus / Q000473:pathology*; D066298:In Vitro Techniques; D018782:Maze Learning / Q000502:physiology; D008564:Membrane Potentials / Q000235:genetics; D008569:Memory Disorders / Q000235:genetics* / Q000473:pathology*; D051379:Mice; D008810:Mice, Inbred C57BL; D008822:Mice, Transgenic; D009043:Motor Activity / Q000235:genetics; D009474:Neurons / Q000502:physiology*; D018408:Patch-Clamp Techniques; D011401:Promoter Regions, Genetic / Q000502:physiology; D016704:Synapsins / Q000378:metabolism; D014446:Tyrosine 3-Monooxygenase / Q000235:genetics / Q000378:metabolism*; D050599:Vesicular Glutamate Transport Protein 2 / Q000172:deficiency* / Q000235:genetics; D050495:Vesicular Inhibitory Amino Acid Transport Proteins / Q000378:metabolism
chemical_list: C493477:Slc17a6 protein, mouse; D016704:Synapsins; D050599:Vesicular Glutamate Transport Protein 2; D050495:Vesicular Inhibitory Amino Acid Transport Proteins; C492244:Viaat protein, mouse; D015102:3,4-Dihydroxyphenylacetic Acid; D049452:Green Fluorescent Proteins; D014446:Tyrosine 3-Monooxygenase; D004298:Dopamine