Ghrelin signalling in AgRP neurons links metabolic state to the sensory regulation of AgRP neural activity.
Ghrelin signalling in AgRP neurons links metabolic state to the sensory regulation of AgRP neural activity.
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DOI：
10.1016/j.molmet.2023.101826
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发表时间：
2023-12
影响因子：
8.1
通讯作者：
Andrews, Zane B.
中科院分区：
文献类型：
--
作者：
So, Wang Lok;Hu, Jiachen;Jeffs, Lotus;Dempsey, Harry;Lockie, Sarah H.;Zigman, Jeffrey M.;Stark, Romana;Reichenbach, Alex;Andrews, Zane B.
关键词：
对食物和食物线索的感官检测会在食用前抑制刺豚鼠相关肽 (AgRP) 神经元活动，其中最大的抑制是在响应高热量食物或内感受能量需求时发生的。然而，引发适当的 AgRP 神经对食物可用性的外部感官信息做出反应的内感受机制仍有待探索。由于饥饿会增加血浆生长素释放肽，我们假设 AgRP 神经元上的生长素释放肽受体 (GHSR) 信号是一种关键的内感受机制，将能量需求与预测热量可用性的外部感觉线索结合起来。我们使用体内光度测定法，测量了 GCaMP6 施用或禁食对 AgRP 神经活动的影响，并使用 GRAB-DA 测量了 AgRP 神经元中缺乏 ghrelin 受体的小鼠伏核中多巴胺释放的影响。 AgRP 神经元上 GHSR 的缺失会阻止 ghrelin 诱导的食物摄入、动机和 AgRP 活性。食物（花生酱颗粒）或木钉的存在会抑制禁食野生型小鼠的 AgRP 活性，但不会抑制 AgRP 神经元中缺乏 GHSR 的小鼠。同样，在 WT 中腹腔注射 ghrelin 后，花生酱和木钉会增加伏隔核中多巴胺的释放，但 AgRP 神经元中缺乏 GHSR 的小鼠则不会。在禁食的小鼠中没有观察到多巴胺释放的差异。最后，腹膜内注射生长素释放肽并没有直接增加腹侧被盖区的多巴胺神经活动。我们的结果表明，AgRP GHSR 将能量需求的内感受状态与外部感觉信息相结合，以产生 AgRP 神经活动的最佳变化。因此，AgRP 神经元上的生长素释放肽信号不仅仅是在饥饿期间增加 AgRP 活性的反馈信号。 AgRP 神经元上的饥饿素受体将饥饿与感觉信息结合起来，以优化 AgRP 神经活动的变化。 AgRP 生长素释放肽受体是生长素释放肽诱导的食物摄入、寻找食物、动机和 AgRP 活性所必需的。 AgRP 生长素释放肽受体介导对感觉信息的适当 AgRP 抑制反应。生长素释放肽受体影响伏隔核中响应感觉信息的多巴胺释放。外周生长素释放肽注射不会直接增加腹侧被盖区多巴胺神经元的活性。
The sensory detection of food and food cues suppresses Agouti related peptide (AgRP) neuronal activity prior to consumption with greatest suppression occurring in response to highly caloric food or interoceptive energy need. However, the interoceptive mechanisms priming an appropriate AgRP neural response to external sensory information of food availability remain unexplored. Since hunger increases plasma ghrelin, we hypothesized that ghrelin receptor (GHSR) signalling on AgRP neurons is a key interoceptive mechanism integrating energy need with external sensory cues predicting caloric availability. We used in vivo photometry to measure the effects of ghrelin administration or fasting on AgRP neural activity with GCaMP6s and dopamine release in the nucleus accumbens with GRAB-DA in mice lacking ghrelin receptors in AgRP neurons. The deletion of GHSR on AgRP neurons prevented ghrelin-induced food intake, motivation and AgRP activity. The presentation of food (peanut butter pellet) or a wooden dowel suppressed AgRP activity in fasted WT but not mice lacking GHSRs in AgRP neurons. Similarly, peanut butter and a wooden dowel increased dopamine release in the nucleus accumbens after ip ghrelin injection in WT but not mice lacking GHSRs in AgRP neurons. No difference in dopamine release was observed in fasted mice. Finally, ip ghrelin administration did not directly increase dopamine neural activity in the ventral tegmental area. Our results suggest that AgRP GHSRs integrate an interoceptive state of energy need with external sensory information to produce an optimal change in AgRP neural activity. Thus, ghrelin signalling on AgRP neurons is more than just a feedback signal to increase AgRP activity during hunger. Ghrelin receptors on AgRP neurons integrate hunger with sensory information to optimise the change in AgRP neural activity. AgRP ghrelin receptors are required for ghrelin-induced food intake, food-seeking, motivation and AgRP activity. AgRP ghrelin receptors mediate the appropriate AgRP inhibitory response to sensory information. Ghrelin receptors influence dopamine release in the nucleus accumbens in response to sensory information. Peripheral ghrelin injection does not directly increase activity of dopamine neurons in the ventral tegmental area.
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影响因子：
16.2
作者：
Burnett CJ;Li C;Webber E;Tsaousidou E;Xue SY;Brüning JC;Krashes MJ
通讯作者：
Krashes MJ
影响因子：
64.5
作者：
Dietrich MO;Zimmer MR;Bober J;Horvath TL
通讯作者：
Horvath TL
影响因子：
2.7
作者：
Floresco, SB;Seamans, JK;Phillips, AG
通讯作者：
Phillips, AG
影响因子：
25
作者：
Dietrich, Marcelo O.;Bober, Jeremy;Horvath, Tamas L.
通讯作者：
Horvath, Tamas L.
影响因子：
15.9
作者：
Chuang, Jen-Chieh;Perello, Mario;Zigman, Jeffrey M.
通讯作者：
Zigman, Jeffrey M.