Food deprivation drives eating through multiple signals and circuits. Decreased glucose availability (i.e., cytoglucopenia) drives eating and also increases the value of sucrose. Ventral tegmental area (VTA) dopamine neurons (DANs) contribute to the evaluation of taste stimuli, but their role in integrating glucoprivic signals remains unknown. We monitored VTA DAN activity via Cre-dependent expression of a calcium indicator with in vivo fibre photometry. In ad libitum fed rats, intraoral sucrose evoked a phasic increase in DAN activity. To manipulate glucose availability, we administered (intraperitoneal, lateral or fourth ventricular) the antiglycolytic agent 5-thio-D-glucose (5TG), which significantly augmented the phasic DAN activity to sucrose. 5TG failed to alter DAN activity to water or saccharin, suggesting the response was selective for caloric stimuli. 5TG enhancement of sucrose-evoked DAN activity was stronger after fourth ventricular administration, suggesting a critical node of action within the hindbrain. As 5TG also increases blood glucose, in a separate study, we used peripheral insulin, which stimulates eating, to decrease blood glucose—which was associated with increased DAN activity to intraoral sucrose. DAN activity developed to a cue predictive of intraoral sucrose. While 5TG augmented cue-evoked DAN activity, its action was most potent when delivered to the lateral ventricle. Together, the studies point to central glucose availability as a key modulator of phasic DAN activity to food and food-cues. As glucose sensing neurons are known to populate the hypothalamus and brainstem, results suggest differential modulation of cue-evoked and sucrose-evoked DAN activity.

中文翻译：

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蔗糖和蔗糖预测线索引起的多巴胺神经元活动通过葡萄糖可用性的外周和中枢操纵而增强

食物匮乏通过多种信号和回路驱动进食。葡萄糖利用率降低（即细胞葡萄糖减少症）会促进进食，同时也会增加蔗糖的价值。腹侧被盖区（VTA）多巴胺神经元（DAN）有助于味觉刺激的评估，但它们在整合糖皮质激素信号中的作用仍然未知。我们通过体内纤维光度测定法通过钙指示剂的 Cre 依赖性表达来监测 VTA DAN 活性。在随意喂养的大鼠中，口腔内蔗糖引起 DAN 活性的阶段性增加。为了控制葡萄糖的可用性，我们给予（腹膜内、侧脑室或第四心室）抗糖酵解剂 5-硫代-D-葡萄糖 (5TG)，它显着增强了蔗糖的相 DAN 活性。5TG 未能改变 DAN 对水或糖精的活性，表明该反应对热量刺激具有选择性。在第四脑室给药后，5TG 对蔗糖诱发的 DAN 活性的增强更强，表明后脑内有一个关键的作用节点。由于 5TG 也会增加血糖，因此在另一项研究中，我们使用刺激进食的外周胰岛素来降低血糖——这与口腔内蔗糖的 DAN 活性增加有关。DAN 活性可作为口腔内蔗糖的预测线索。虽然 5TG 增强了提示诱发的 DAN 活性，但当传递到侧脑室时，其作用最为有效。总之，这些研究表明，中央葡萄糖可用性是食物和食物线索阶段性 DAN 活性的关键调节剂。由于已知葡萄糖感应神经元分布在下丘脑和脑干，因此结果表明提示诱发和蔗糖诱发的 DAN 活性存在差异调节。