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食欲由孤束核至下丘脑神经回路中的胆囊收缩素核所控制。

Appetite controlled by a cholecystokinin nucleus of the solitary tract to hypothalamus neurocircuit.

作者信息

D'Agostino Giuseppe, Lyons David J, Cristiano Claudia, Burke Luke K, Madara Joseph C, Campbell John N, Garcia Ana Paula, Land Benjamin B, Lowell Bradford B, Dileone Ralph J, Heisler Lora K

机构信息

Rowett Institute of Nutrition and Health, University of Aberdeen, Aberdeen, United Kingdom.

Department of Pharmacology, University of Cambridge, Cambridge, United Kingdom.

出版信息

Elife. 2016 Mar 14;5:e12225. doi: 10.7554/eLife.12225.

DOI:10.7554/eLife.12225
PMID:26974347
原文链接:https://pmc.ncbi.nlm.nih.gov/articles/PMC4861598/
Abstract

The nucleus of the solitary tract (NTS) is a key gateway for meal-related signals entering the brain from the periphery. However, the chemical mediators crucial to this process have not been fully elucidated. We reveal that a subset of NTS neurons containing cholecystokinin (CCK(NTS)) is responsive to nutritional state and that their activation reduces appetite and body weight in mice. Cell-specific anterograde tracing revealed that CCK(NTS) neurons provide a distinctive innervation of the paraventricular nucleus of the hypothalamus (PVH), with fibers and varicosities in close apposition to a subset of melanocortin-4 receptor (MC4R(PVH)) cells, which are also responsive to CCK. Optogenetic activation of CCK(NTS) axon terminals within the PVH reveal the satiating function of CCK(NTS) neurons to be mediated by a CCK(NTS)→PVH pathway that also encodes positive valence. These data identify the functional significance of CCK(NTS) neurons and reveal a sufficient and discrete NTS to hypothalamus circuit controlling appetite.

摘要

孤束核（NTS）是外周与进食相关信号进入大脑的关键门户。然而，这一过程中至关重要的化学介质尚未完全阐明。我们发现，一部分含有胆囊收缩素的NTS神经元（CCK（NTS））对营养状态有反应，并且它们的激活会降低小鼠的食欲和体重。细胞特异性顺行示踪显示，CCK（NTS）神经元对下丘脑室旁核（PVH）有独特的神经支配，其纤维和曲张体与一部分促黑素皮质素4受体（MC4R（PVH））细胞紧密相邻，这些细胞也对CCK有反应。对PVH内CCK（NTS）轴突终末进行光遗传学激活，揭示了CCK（NTS）神经元的饱腹感功能是由CCK（NTS）→PVH通路介导的，该通路也编码积极情绪效价。这些数据确定了CCK（NTS）神经元的功能意义，并揭示了一条从NTS到下丘脑的、足以控制食欲的离散神经回路。

https://cdn.ncbi.nlm.nih.gov/pmc/blobs/9d58/4861598/6c35d24943c0/elife-12225-fig4.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/9d58/4861598/47fa929dac75/elife-12225-fig1.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/9d58/4861598/a6dab4aaddde/elife-12225-fig2.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/9d58/4861598/a9d43a13f8ab/elife-12225-fig3.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/9d58/4861598/a920aba2ded5/elife-12225-fig3-figsupp1.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/9d58/4861598/3e790e7b11e6/elife-12225-fig3-figsupp2.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/9d58/4861598/fa9b8b9067e0/elife-12225-fig3-figsupp3.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/9d58/4861598/6c35d24943c0/elife-12225-fig4.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/9d58/4861598/47fa929dac75/elife-12225-fig1.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/9d58/4861598/a6dab4aaddde/elife-12225-fig2.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/9d58/4861598/a9d43a13f8ab/elife-12225-fig3.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/9d58/4861598/a920aba2ded5/elife-12225-fig3-figsupp1.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/9d58/4861598/3e790e7b11e6/elife-12225-fig3-figsupp2.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/9d58/4861598/fa9b8b9067e0/elife-12225-fig3-figsupp3.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/9d58/4861598/6c35d24943c0/elife-12225-fig4.jpg

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