Journal
BRAIN STRUCTURE & FUNCTION
Volume 220, Issue 4, Pages 2171-2190Publisher
SPRINGER HEIDELBERG
DOI: 10.1007/s00429-014-0778-9
Keywords
Reward; Oscillations; Development; Midbrain; Mouse genetics
Categories
Funding
- Swedish Medical Research Council [2007-5742, 2011-4747]
- Uppsala University
- Swedish Brain Foundation
- Parkinsonfonden
- foundation of Major Gosta Lind
- foundation of Ake Wiberg
- foundation of Ahlen
- foundation of Bertil Hallsten
- Intramural Research Program of the National Institute on Drug Abuse
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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.
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