小柯机器人

美国哈佛医学院Bradford B. Lowell团队发现，AGRP饥饿神经元通过食物线索指导学习。相关论文于2021年7月14日在线发表在《自然》杂志上。

据研究人员介绍，表达Agouti相关肽（AGRP）的神经元被禁食所激活，这导致饥饿，一种厌恶状态，促使人们寻求和摄入食物。进食使AGRP神经元的活动在三个不同的时间尺度上恢复到基线：在感觉到食物线索后迅速而短暂地恢复；在对肠道内营养物质的反应中缓慢而持久地恢复；甚至在能量平衡恢复后更缓慢而持久地恢复。食物线索的快速调节是特别令人感兴趣的，因为其神经生物学基础和目的是未知的。鉴于AGRP神经元的活动是厌恶性的，与感觉线索相关的活动减少可以起到指导行为的作用。

为了评估这一点，研究人员首先确定了介导感觉线索抑制的回路，然后选择性地扰乱它来确定其功能。结果表明，下丘脑外侧谷氨酸能→下丘脑背内侧GABA能（γ-氨基丁酸分泌）→AGRP神经元回路介导这一调节。干扰这个回路会损害食物线索对AGRP神经元的抑制作用，特别是会大大损害对感觉线索引发的食物获取任务的学习。这是对食物的特定影响，因为对相同的水获取任务的学习不受影响。研究人员提出，由这种食物特异性回路介导的厌恶性AGRP神经元活动的减少能够增加食物线索的激励显著性，从而促进食物获取任务的学习。

附：英文原文

Title: Food cue regulation of AGRP hunger neurons guides learning

Author: Janet Berrios, Chia Li, Joseph C. Madara, Alastair S. Garfield, Jennifer S. Steger, Michael J. Krashes, Bradford B. Lowell

Issue&Volume: 2021-07-14

Abstract: Agouti-related peptide (AGRP)-expressing neurons are activated by fasting—this causes hunger1,2,3,4, an aversive state that motivates the seeking and consumption of food5,6. Eating returns AGRP neuron activity towards baseline on three distinct timescales: rapidly and transiently following sensory detection of food cues6,7,8, slowly and longer-lasting in response to nutrients in the gut9,10, and even more slowly and permanently with restoration of energy balance9,11. The rapid regulation by food cues is of particular interest as its neurobiological basis and purpose are unknown. Given that AGRP neuron activity is aversive6, the sensory cue-linked reductions in activity could function to guide behaviour. To evaluate this, we first identified the circuit mediating sensory cue inhibition and then selectively perturbed it to determine function. Here, we show that a lateral hypothalamic glutamatergic → dorsomedial hypothalamic GABAergic (γ-aminobutyric acid-producing)12 → AGRP neuron circuit mediates this regulation. Interference with this circuit impairs food cue inhibition of AGRP neurons and, notably, greatly impairs learning of a sensory cue-initiated food-acquisition task. This is specific for food, as learning of an identical water-acquisition task is unaffected. We propose that decreases in aversive AGRP neuron activity6 mediated by this food-specific circuit increases the incentive salience13 of food cues, and thus facilitates the learning of food-acquisition tasks.

DOI: 10.1038/s41586-021-03729-3

Source: https://www.nature.com/articles/s41586-021-03729-3

Nature：《自然》，创刊于1869年。隶属于施普林格·自然出版集团，最新IF：69.504
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