Lateral hypothalamic orexin glucose-inhibited neurons may regulate reward-based feeding by modulating glutamate transmission in the ventral tegmental area.
Lateral hypothalamic orexin glucose-inhibited neurons may regulate reward-based feeding by modulating glutamate transmission in the ventral tegmental area.
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DOI：
10.1016/j.brainres.2018.05.025
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发表时间：
2020-03-15
期刊：
影响因子：
2.9
通讯作者：
Routh VH
中科院分区：
文献类型：
--
作者：
Teegala SB;Sheng Z;Dalal MS;Hirschberg PR;Beck KD;Routh VH
葡萄糖抑制约 60% 的外侧下丘脑 (LH) 食欲素神经元。禁食会增加低血糖条件下 LH 食欲素葡萄糖抑制 (GI) 神经元的激活。在低葡萄糖条件下，推定的 VTA DA 神经元上的自发谷氨酸兴奋性突触后电流 (sEPSC) 的增加是食欲素依赖性的。 VTA DA 神经元调节基于奖励的喂养。我们测试了这样的假设：低葡萄糖条件下 LH 食欲素-GI 神经元的激活增加会增加 VTA DA 神经元上的谷氨酸信号传导，并有助于限制食物动物的基于奖励的喂养。使用包含 LH 和 VTA 的水平脑切片中的全细胞电压钳记录来测量推定的 VTA DA 神经元上的 N-甲基-D-天冬氨酸 (NMDA) 和 α-氨基-3-羟基-5-甲基-4-异恶唑丙酸 (AMPA) 电流。在血糖恢复到基础水平后，血糖降低至少会增加 NMDA 受体电流至少一小时（P < 0.05；N = 8）。增加的电流被食欲素 1 受体拮抗剂阻断（P < 0.05；N = 5）。低葡萄糖引起类似的 AMPA 受体电流持续增强（P < 0.05；N = 7）。禁食过夜会增加假定的 VTA DA 神经元上的 AMPA/NMDA 受体电流比（体内谷氨酸可塑性指数）。在用葡萄糖进行 LH 透析期间测量了对可口食物的条件性位置偏好 (CPP)。 CPP 评分与 LH 葡萄糖增加呈负相关（P < 0.05；N = 20）。这些数据表明，减肥后低血糖条件下 LH 食欲素-GI 神经元的激活增加，导致 VTA DA 神经元上的谷氨酸信号增强，增加吃有益食物的动力，并可能有助于体重反弹。
Glucose inhibits ~60% of lateral hypothalamic (LH) orexin neurons. Fasting increases the activation of LH orexin glucose-inhibited (GI) neurons in low glucose. Increases in spontaneous glutamate excitatory postsynaptic currents (sEPSCs) onto putative VTA DA neurons in low glucose are orexin dependent. VTA DA neurons modulate reward-based feeding. We tested the hypothesis that increased activation of LH orexin-GI neurons in low glucose increases glutamate signaling onto VTA DA neurons and contributes to reward-based feeding in food restricted animals. N-methyl-D-aspartate (NMDA) and α-amino-3-hydroxy-5-methyl-4-isoxazolepropionic acid (AMPA) currents on putative VTA DA neurons were measured using whole cell voltage clamp recording in horizontal brain slices containing the LH and VTA. Decreased glucose increased the NMDA receptor current for at least one hour after returning glucose to basal levels (P < 0.05; N = 8). The increased current was blocked by an orexin 1 receptor antagonist (P < 0.05; N = 5). Low glucose caused a similar persistent enhancement of AMPA receptor currents (P < 0.05; N = 7). An overnight fast increased the AMPA/NMDA receptor current ratio, an in vivo index of glutamate plasticity, on putative VTA DA neurons. Conditioned place preference (CPP) for palatable food was measured during LH dialysis with glucose. CPP score was negatively correlated with increasing LH glucose (P < 0.05; N = 20). These data suggest that increased activation of LH orexin-GI neurons in low glucose after weight loss, leads to enhanced glutamate signaling on VTA DA neurons, increases the drive to eat rewarding food, and may contribute to weight regain.
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