连接两个糖传感器的神经回路调节果蝇的饱腹感依赖性果糖驱动

来源: Pierre-Yves Musso et al 发布日期: 2022-03-10 访问量: 182

导读	在果蝇体内，神经元传感器检测循环果糖水平的饮食变化，并根据内部状态维持或终止进食。在这里，我们描述了一个由三部分组成的神经电路，该电路对果糖感应进行饱足依赖性调节... 标签: 果蝇进食、糖传感器、糖饱腹感、神经回路

A neural circuit linking two sugar sensors regulates satiety-dependent fructose drive in Drosophila

连接两个糖传感器的神经回路调节果蝇的饱腹感依赖性果糖驱动

Pierre-Yves Musso, Pierre Junca, Michael D. Gordon*

Copyright © 2021 The Authors, some rights reserved; exclusive licensee American Association for the Advancement of Science. No claim to original U.S. Government Works. Distributed under a Creative Commons Attribution NonCommercial License 4.0 (CC BY-NC).

Abstract

In flies, neuronal sensors detect prandial changes in circulating fructose levels and either sustain or terminate feeding, depending on internal state. Here, we describe a three-part neural circuit that imparts satiety-dependent modulation of fructose sensing. We show that dorsal fan-shaped body neurons display oscillatory calcium activity when hemolymph glucose is high and that these oscillations require glutamatergic input from SLP-AB or “Janus” neurons projecting from the protocerebrum to the asymmetric body. Suppression of activity in this circuit, either by starvation or by genetic silencing, promotes specific drive for fructose ingestion. This is achieved through neuropeptidergic signaling by tachykinin, which is released from the fan-shaped body when glycemia is high. Tachykinin, in turn, signals to Gr43a-positive fructose sensors to modulate their response to fructose. Together, our results demonstrate how a three-layer neural circuit links the detection of two sugars to produce precise satiety-dependent control of feeding behavior.

在果蝇体内，神经元传感器检测循环果糖水平的饮食变化，并根据内部状态维持或终止进食。在这里，我们描述了一个由三部分组成的神经电路，该电路对果糖感应进行饱足依赖性调节。我们发现，当血淋巴葡萄糖浓度较高时，背侧扇形体神经元表现出振荡性钙活动，这些振荡需要来自SLP-AB或“Janus”神经元的谷氨酸能输入，这些神经元从前脑投射到不对称体。通过饥饿或基因沉默抑制这一回路的活动，可以促进果糖摄入的特定驱动力。这是通过速激肽释放的神经肽能信号实现的，当血糖升高时，速激肽从扇形体内释放。速激肽反过来向Gr43a阳性果糖传感器发出信号，以调节它们对果糖的反应。总之，我们的结果证明了三层神经回路如何将两种糖的检测联系起来，从而对进食行为产生精确的饱腹感依赖控制。

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FIG. 2. Silencing dFB neurons increases fructose feeding.

(A) Immunofluorescent detection of UAS-GFP driven by R70H05-GAL4. (B) Experimental timeline: Flies are placed at 29°C for 47 hours and starved for 18 hours, and experiments are performed at 25°C . (C) Experimental setup: One channel is filled with sugar and the other one is filled with 1% agar. (D) Effect of dFB neuron silencing on interactions with various concentrations of sucrose (5, 50, and 1000 mM; n = 16 to 21). UAS-Kir^ts represents UAS-Kir2.1 plus tub-Gal80^ts. (E) Effect of dFB neuron silencing on interactions with various concentrations of L-glucose (5, 50, and 1000 mM; n = 10 to 19). (F) Effect of dFB neuron silencing on interactions with 50 mM D-sorbitol (n = 15). (G) Effect of dFB neuron silencing on interactions with 50 mM L-glucose mixed with various concentrations of D-sorbitol (0, 5, 50, 200, and 1000 mM; n = 10 to 16). (H) Effect of dFB neuron silencing on interactions with various concentrations of D-glucose (5, 50, and 1000 mM; n = 8 to 26). (I) Effect of dFB neuron silencing on flies’ interactions with various concentrations of fructose (5, 50, and 1000 mM; n = 11 to 17). Values represent mean ± SEM. Statistical tests: one-way ANOVA and Tukey post hoc; ns, P > 0.05; *P < 0.05; **P < 0.01; ***P < 0.001.

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flyPAD experiments

All flies were 5 to 9 days old at the time of the assay, and experiments were performed between 10:00 a.m. and 5:00 p.m. For single-tastant experiments, one channel of the arena was loaded with 3.5 μl of 1% agar mixed with a tastant. To exclude interactions due to drinking behavior, the other side was loaded with 3.5 μl of 1% agar. The tastants used were sucrose (5, 50, and 1000 mM), L-glucose (5, 50, and 1000 mM), 50 mM L-glucose combined with D-sorbitol (0, 5, 50, 500, and 1000 mM), D-glucose (5, 50, and 1000 mM), fructose (5, 50, and 1000 mM), and D-sorbitol (50 mM). For dual-tastant experiments, one channel was loaded with fructose, while the other one was loaded with D-glucose, always in an equimolar manner (5, 50, and 1000 mM). Acquisition on the flyPAD software was started, and then single flies were transferred into each arena by mouth aspiration. Experiments were run for 60 min, and the preference index (PI) for each fly was calculated as: (interactions with food 1 – interactions with food 2)/(interactions with food 1 + interactions with from food 2). Tastants were all obtained from Sigma-Aldrich.

原文链接：https://www.science.org/doi/full/10.1126/sciadv.abj0186

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