RT Journal Article
SR Electronic
T1 VMAT2-Mediated Neurotransmission from Midbrain Leptin Receptor Neurons in Feeding Regulation
JF eneuro
JO eNeuro
FD Society for Neuroscience
SP ENEURO.0083-17.2017
DO 10.1523/ENEURO.0083-17.2017
VO 4
IS 3
A1 Yuanzhong Xu
A1 Yungang Lu
A1 Pingwen Xu
A1 Leandra R. Mangieri
A1 Elsa Isingrini
A1 Yong Xu
A1 Bruno Giros
A1 Qingchun Tong
YR 2017
UL http://www.eneuro.org/content/4/3/ENEURO.0083-17.2017.abstract
AB Leptin receptors (LepRs) expressed in the midbrain contribute to the action of leptin on feeding regulation. The midbrain neurons release a variety of neurotransmitters including dopamine (DA), glutamate and GABA. However, which neurotransmitter mediates midbrain leptin action on feeding remains unclear. Here, we showed that midbrain LepR neurons overlap with a subset of dopaminergic, GABAergic and glutamatergic neurons. Specific removal of vesicular monoamine transporter 2 (VMAT2) in midbrain LepR neurons (KO mice) disrupted DA accumulation in vesicles, but failed to cause a significant change in the evoked release of either glutamate or GABA to downstream neurons. While KO mice showed no differences on chow, they presented a reduced high-fat diet (HFD) intake and resisted to HFD-induced obesity. Specific activation of midbrain LepR neurons promoted VMAT2-dependent feeding on chow and HFD. When tested with an intermittent access to HFD where first 2.5-h HFD eating (binge-like) and 24-h HFD feeding were measured, KO mice exhibited more binge-like, but less 24-h HFD feeding. Interestingly, leptin inhibited 24-h HFD feeding in controls but not in KO mice. Thus, VMAT2-mediated neurotransmission from midbrain LepR neurons contributes to both binge-like eating and HFD feeding regulation.