Department of Translational Neuroscience, Brain Center Rudolf Magnus, University Medical Center Utrecht, Utrecht University, Utrecht, The Netherlands.
Institute of Neuroscience and Physiology, Sahlgrenska Academy, University of Gothenburg, Medicinaregatan 11, Göteborg, 41390, Sweden.
J Physiol. 2021 Jan;599(2):709-724. doi: 10.1113/JP276513. Epub 2020 Dec 22.
The zona incerta (ZI) and ventral tegmental area (VTA) are brain areas that are both implicated in feeding behaviour. The ZI projects to the VTA, although it has not yet been investigated whether this projection regulates feeding. We experimentally (in)activated the ZI to VTA projection by using dual viral vector technology, and studied the effects on feeding microstructure, the willingness to work for food, general activity and body temperature. Activity of the ZI to VTA projection promotes feeding by facilitating action initiation towards food, as reflected in meal frequency and the willingness to work for food reward, without affecting general activity or directly modulating body temperature. We show for the first time that activity of the ZI to VTA projection promotes feeding, which improves the understanding of the neurobiology of feeding behaviour and body weight regulation.
Both the zona incerta (ZI) and the ventral tegmental area (VTA) have been implicated in feeding behaviour. The ZI provides prominent input to the VTA, although it has not yet been investigated whether this projection regulates feeding. Therefore, we investigated the role of ZI to VTA projection neurons in the regulation of several aspects of feeding behaviour. We determined the effects of (in)activation of ZI to VTA projection neurons on feeding microstructure, food-motivated behaviour under a progressive ratio schedule of reinforcement, locomotor activity and core body temperature. To activate or inactivate ZI neurons projecting to the VTA, we used a combination of canine adenovirus-2 in the VTA, as well as Cre-dependent designer receptors exclusively activated by designer drugs (DREADD) or tetanus toxin (TetTox) light chain in the ZI. TetTox-mediated inactivation of ZI to VTA projection neurons reduced food-motivated behaviour and feeding by reducing meal frequency. Conversely, DREADD-mediated chemogenetic activation of ZI to VTA projection neurons promoted food-motivated behaviour and feeding. (In)activation of ZI to VTA projection neurons did not affect locomotor activity or directly regulate core body temperature. Taken together, ZI neurons projecting to the VTA exert bidirectional control overfeeding behaviour. More specifically, activity of ZI to VTA projection neurons facilitate action initiation towards feeding, as reflected in both food-motivated behaviour and meal initiation, without affecting general activity.
缰核（ZI）和腹侧被盖区（VTA）均与摄食行为有关。ZI 投射到 VTA，但尚未研究该投射是否调节摄食。我们使用双病毒载体技术对 ZI 到 VTA 的投射进行了实验性（in）激活，并研究了其对摄食微结构、对食物奖励的工作意愿、一般活动和体温的影响。ZI 到 VTA 投射的活动通过促进对食物的动作启动来促进摄食，这反映在进食频率和对食物奖励的工作意愿上，而不影响一般活动或直接调节体温。我们首次表明，ZI 到 VTA 投射的活动促进摄食，这提高了对摄食行为和体重调节神经生物学的理解。
缰核（ZI）和腹侧被盖区（VTA）都与摄食行为有关。ZI 对 VTA 提供了显著的输入，尽管尚未研究该投射是否调节摄食。因此，我们研究了 ZI 到 VTA 投射神经元在调节摄食行为的几个方面中的作用。我们确定了激活或失活 VTA 投射神经元对摄食微结构、强化比例程序下的食物动机行为、运动活动和核心体温的影响。为了激活或失活投射到 VTA 的 ZI 神经元，我们在 VTA 中使用了犬腺病毒-2，以及在 ZI 中使用 Cre 依赖性设计受体仅被设计药物（DREADD）或破伤风毒素（TetTox）轻链激活。TetTox 介导的 ZI 到 VTA 投射神经元失活减少了进食动机行为和进食，减少了进食频率。相反，DREADD 介导的 ZI 到 VTA 投射神经元的化学遗传激活促进了食物动机行为和进食。（In）失活 ZI 到 VTA 投射神经元不影响运动活动或直接调节核心体温。总之，投射到 VTA 的 ZI 神经元对摄食行为施加双向控制。更具体地说，ZI 到 VTA 投射神经元的活动促进了摄食的动作启动，这反映在食物动机行为和进食开始上，而不影响一般活动。
