caa a22 4500 606202382 CHVBK 20210128100952.0 cr unu---uuuuu 210128e20150701xx s 000 0 eng 10.1007/s00429-014-0778-9 doi (NATIONALLICENCE)springer-10.1007/s00429-014-0778-9 Increased hippocampal excitability and impaired spatial memory function in mice lacking VGLUT2 selectively in neurons defined by tyrosine hydroxylase promoter activity [Elektronische Daten] [Karin Nordenankar, Casey Smith-Anttila, Nadine Schweizer, Thomas Viereckel, Carolina Birgner, Jana Mejia-Toiber, Marisela Morales, Richardson Leao, Åsa Wallén-Mackenzie] 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. The Author(s), 2014 Reward nationallicence Oscillations nationallicence Development nationallicence Midbrain nationallicence Mouse genetics nationallicence β-Gal : β-Galactosidase nationallicence CaPu : Caudate putamen nationallicence cKO : Conditional knockout nationallicence CLi : Caudal linear nucleus nationallicence Ctrl : Control nationallicence DA : Dopamine nationallicence DAB : 3,3-Diaminobenzidine-4 nationallicence DAPI : 4′,6′-Diamidino-2-phenylindole nationallicence DAT : Dopamine transporter nationallicence DOPAC : 3,4-Dihydroxyphenylacetic acid nationallicence DRG : Dorsal root ganglia nationallicence EPM : Elevated plus maze nationallicence FST : Forced swim test nationallicence GFP : Green fluorescent protein nationallicence HVA : Homovanillic acid nationallicence IF : Interfascicular nucleus nationallicence IHC : Immunohistochemistry nationallicence KRB : Krebs-Ringer buffer nationallicence LFP : Local field potential nationallicence lVTA : Later ventral tegmental area nationallicence MFB : Medial forebrain bundle nationallicence NAcc : Nucleus accumbens nationallicence PB : Phosphate buffer nationallicence PFA : Paraformaldehyde nationallicence PFC : Prefrontal cortex nationallicence RLi : Rostral linear nucleus nationallicence RME : Reference memory error nationallicence SNc : Substantia nigra pars compacta nationallicence SSC : Saline-sodium citrate nationallicence TH : Tyrosine hydroxylase nationallicence TUJ1 : Beta-III-tubulin nationallicence Vglut2 : Vesicular glutamate transporter 2 nationallicence VIAAT : Vesicular inhibitory amino acid transporter nationallicence VTA : Ventral tegmental area nationallicence WME : Working memory error nationallicence Nordenankar Karin Unit of Functional Neurobiology and Unit of Developmental Genetics, Biomedical Center, Department of Neuroscience, Uppsala University, Box 593, S-751 24, Uppsala, Sweden aut Smith-Anttila Casey Unit of Functional Neurobiology and Unit of Developmental Genetics, Biomedical Center, Department of Neuroscience, Uppsala University, Box 593, S-751 24, Uppsala, Sweden aut Schweizer Nadine Unit of Functional Neurobiology and Unit of Developmental Genetics, Biomedical Center, Department of Neuroscience, Uppsala University, Box 593, S-751 24, Uppsala, Sweden aut Viereckel Thomas Unit of Functional Neurobiology and Unit of Developmental Genetics, Biomedical Center, Department of Neuroscience, Uppsala University, Box 593, S-751 24, Uppsala, Sweden aut Birgner Carolina Unit of Functional Neurobiology and Unit of Developmental Genetics, Biomedical Center, Department of Neuroscience, Uppsala University, Box 593, S-751 24, Uppsala, Sweden aut Mejia-Toiber Jana National Institute on Drug Abuse, Intramural Research Program, Neuronal Networks Section, 251 Bayview Boulevard, 21224, Baltimore, MD, USA aut Morales Marisela National Institute on Drug Abuse, Intramural Research Program, Neuronal Networks Section, 251 Bayview Boulevard, 21224, Baltimore, MD, USA aut Leao Richardson Brain Institute, Federal University of Rio Grande do Norte, 2155 - 59056-450, Natal/RN, Brazil aut Wallén-Mackenzie Åsa Unit of Functional Neurobiology and Unit of Developmental Genetics, Biomedical Center, Department of Neuroscience, Uppsala University, Box 593, S-751 24, Uppsala, Sweden aut Brain Structure and Function Springer Berlin Heidelberg 220/4(2015-07-01), 2171-2190 1863-2653 220:4<2171 2015 220 429 https://doi.org/10.1007/s00429-014-0778-9 text/html Onlinezugriff via DOI BK010053 XK010053 XK010000 Metadata rights reserved Springer special CC-BY-NC licence nationallicence 1 research-article jats NATIONALLICENCE NATIONALLICENCE NL-springer NATIONALLICENCE 856 40 https://doi.org/10.1007/s00429-014-0778-9 text/html Onlinezugriff via DOI NATIONALLICENCE 700 1- Nordenankar Karin Unit of Functional Neurobiology and Unit of Developmental Genetics, Biomedical Center, Department of Neuroscience, Uppsala University, Box 593, S-751 24, Uppsala, Sweden aut NATIONALLICENCE 700 1- Smith-Anttila Casey Unit of Functional Neurobiology and Unit of Developmental Genetics, Biomedical Center, Department of Neuroscience, Uppsala University, Box 593, S-751 24, Uppsala, Sweden aut NATIONALLICENCE 700 1- Schweizer Nadine Unit of Functional Neurobiology and Unit of Developmental Genetics, Biomedical Center, Department of Neuroscience, Uppsala University, Box 593, S-751 24, Uppsala, Sweden aut NATIONALLICENCE 700 1- Viereckel Thomas Unit of Functional Neurobiology and Unit of Developmental Genetics, Biomedical Center, Department of Neuroscience, Uppsala University, Box 593, S-751 24, Uppsala, Sweden aut NATIONALLICENCE 700 1- Birgner Carolina Unit of Functional Neurobiology and Unit of Developmental Genetics, Biomedical Center, Department of Neuroscience, Uppsala University, Box 593, S-751 24, Uppsala, Sweden aut NATIONALLICENCE 700 1- Mejia-Toiber Jana National Institute on Drug Abuse, Intramural Research Program, Neuronal Networks Section, 251 Bayview Boulevard, 21224, Baltimore, MD, USA aut NATIONALLICENCE 700 1- Morales Marisela National Institute on Drug Abuse, Intramural Research Program, Neuronal Networks Section, 251 Bayview Boulevard, 21224, Baltimore, MD, USA aut NATIONALLICENCE 700 1- Leao Richardson Brain Institute, Federal University of Rio Grande do Norte, 2155 - 59056-450, Natal/RN, Brazil aut NATIONALLICENCE 700 1- Wallén-Mackenzie Åsa Unit of Functional Neurobiology and Unit of Developmental Genetics, Biomedical Center, Department of Neuroscience, Uppsala University, Box 593, S-751 24, Uppsala, Sweden aut NATIONALLICENCE 773 0- Brain Structure and Function Springer Berlin Heidelberg 220/4(2015-07-01), 2171-2190 1863-2653 220:4<2171 2015 220 429