5-HT recruits distinct neurocircuits to inhibit hunger-driven and non-hunger-driven feeding.

5-HT recruits distinct neurocircuits to inhibit hunger-driven and non-hunger-driven feeding.
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DOI:
10.1038/s41380-021-01220-z
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发表时间:
2021-12
影响因子:
11
通讯作者:
Xu Y
Xu Y
中科院分区:
医学1区
文献类型:
--
作者:
He Y;Cai X;Liu H;Conde KM;Xu P;Li Y;Wang C;Yu M;He Y;Liu H;Liang C;Yang T;Yang Y;Yu K;Wang J;Zheng R;Liu F;Sun Z;Heisler L;Wu Q;Tong Q;Zhu C;Shu G;Xu Y

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肥胖主要是由于摄入的热量超过能量需求而导致的,但其背后的驱动因素尚未完全明确。中缝背核 (5-HTDRN) 中的 5-羟色胺 (5-HT) 神经元调节不同类型的进食行为,例如为了应对饥饿或为了愉悦而进食。在这里,我们观察到激活下丘脑弓状核(5-HTDRN → ARH)投射的5-HTDRN通过ARH 5-HT2C和5-HT1B受体的作用抑制饥饿驱动的食物摄入,而激活腹侧被盖区(5-HTDRN → VTA)5-HTDRN投射则通过作用于ARH 5-HT2C和5-HT1B受体抑制非饥饿驱动的进食。 5-HT2C 受体。此外,饥饿驱动的进食通过抑制 ARH 投射 5-HTDRN 神经元对抑制性 GABA 能输入的反应,逐渐激活它们;非饥饿驱动的进食通过减少钾外向电流来激活 VTA 投射的 5-HTDRN 神经元。因此,我们的结果支持一个模型,通过该模型,并行电路可以响应饥饿或独立于饥饿的线索来调节进食行为。
Obesity is primarily a consequence of consuming calories beyond energetic requirements, but underpinning drivers have not been fully defined. 5-Hydroxytryptamine (5-HT) neurons in the dorsal Raphe nucleus (5-HTDRN) regulate different types of feeding behavior, such as eating to cope with hunger or for pleasure. Here, we observed that activation of 5-HTDRN to hypothalamic arcuate nucleus (5-HTDRN → ARH) projections inhibits food intake driven by hunger via actions at ARH 5-HT2C and 5-HT1B receptors, whereas activation of 5-HTDRN to ventral tegmental area (5-HTDRN → VTA) projections inhibits non-hunger-driven feeding via actions at 5-HT2C receptors. Further, hunger-driven feeding gradually activates ARH-projecting 5-HTDRN neurons via inhibiting their responsiveness to inhibitory GABAergic inputs; non-hunger-driven feeding activates VTA-projecting 5-HTDRN neurons through reducing a potassium outward current. Thus, our results support a model whereby parallel circuits modulate feeding behavior either in response to hunger or to hunger-independent cues.
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