TY - JOUR T1 - VMAT2-Mediated Neurotransmission from Midbrain Leptin Receptor Neurons in Feeding Regulation JF - eneuro JO - eNeuro DO - 10.1523/ENEURO.0083-17.2017 VL - 4 IS - 3 SP - ENEURO.0083-17.2017 AU - Yuanzhong Xu AU - Yungang Lu AU - Pingwen Xu AU - Leandra R. Mangieri AU - Elsa Isingrini AU - Yong Xu AU - Bruno Giros AU - Qingchun Tong Y1 - 2017/05/01 UR - http://www.eneuro.org/content/4/3/ENEURO.0083-17.2017.abstract N2 - 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. ER -