Hunger enhances food-odour attraction through a neuropeptide Y spotlight.
Hunger enhances food-odour attraction through a neuropeptide Y spotlight.
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DOI：
10.1038/s41586-021-03299-4
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发表时间：
2021-04
期刊：
影响因子：
64.8
通讯作者：
Liberles SD
中科院分区：
文献类型：
--
作者：
Horio N;Liberles SD
内部状态控制嗅觉通过知之甚少的机制。象征食物、配偶、竞争者和捕食者的气味会激活平行的神经回路，这些神经回路可能会根据生理需要灵活地塑造，以改变行为结果。在这里，我们确定了一种神经元机制，饥饿选择性地促进吸引力的食物气味超过其他嗅觉线索。下丘脑Agouti-Related Peptide（AGRP）神经元的光遗传激活增强了对食物气味的吸引力，但不增强对信息素的吸引力，分支特异性激活和抑制揭示了向室旁丘脑投射的关键作用。缺乏神经肽Y（NPY）或5型神经肽Y受体（NPY5R）的敲除小鼠在禁食后不能偏好食物气味而不是信息素，AGRP神经元中的细胞特异性NPY拯救恢复了饥饿依赖的食物气味吸引力。此外，急性神经肽Y注射立即挽救行为，而无需额外的训练，表明在行为表达期间阅读嗅觉回路所需的神经肽Y，而不是在气味学习期间写入嗅觉回路。总之，这些研究结果表明，食物气味反应神经元组成了一个嗅觉子回路，通过丘脑NPY释放来倾听饥饿状态，更普遍地说，提供了对内部状态如何调节行为的机械见解。
Internal state controls olfaction through poorly understood mechanisms. Odors signifying food, mates, competitors, and predators activate parallel neural circuits that may be flexibly shaped by physiological need to alter behavioral outcome. Here, we identify a neuronal mechanism by which hunger selectively promotes attraction to food odors over other olfactory cues. Optogenetic activation of hypothalamic Agouti-Related Peptide (AGRP) neurons enhances attraction to food odors but not pheromones, with branch-specific activation and inhibition revealing a key role for projections to the paraventricular thalamus. Knockout mice lacking Neuropeptide Y (NPY) or NPY receptor type 5 (NPY5R) fail to prefer food odors over pheromones after fasting, with hunger-dependent food odor attraction restored by cell-specific NPY rescue in AGRP neurons. Furthermore, acute NPY injection immediately rescues behavior without additional training, indicating that NPY is required for reading olfactory circuits during behavioral expression rather than writing olfactory circuits during odor learning. Together, these findings show that food odor-responsive neurons comprise an olfactory subcircuit that listens to hunger state through thalamic NPY release, and more generally, provide mechanistic insights into how internal state regulates behavior.
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