Adaptive sugar sensors in hypothalamic feeding circuits

被引:96
作者
Williams, Rhiannan H. [1 ,2 ]
Alexopoulos, Haris [3 ]
Jensen, Lise T.
Fugger, Lars [3 ,4 ]
Burdakov, Denis [1 ]
机构
[1] Univ Cambridge, Dept Pharmacol, Cambridge C82 1PD, England
[2] Univ Manchester, Fac Life Sci, Manchester M13 9PL, Lancs, England
[3] Univ Oxford, Weatherall Inst Mol Med, Dept Clin Neurol, Oxford OX3 9OS, England
[4] Aarhus Univ Hosp, Inst Clin, DK-8200 Aarhus, Denmark
基金
英国生物技术与生命科学研究理事会; 英国医学研究理事会;
关键词
brain; glucose; hypocretin; orexin; hypothalamus;
D O I
10.1073/pnas.0802687105
中图分类号
O [数理科学和化学]; P [天文学、地球科学]; Q [生物科学]; N [自然科学总论];
学科分类号
07 ; 0710 ; 09 ;
摘要
Brain glucose sensing is critical for healthy energy balance, but how appropriate neurocircuits encode both small changes and large background values of glucose levels is unknown. Here, we report several features of hypothalamic orexin neurons, cells essential for normal wakefulness and feeding: (i) A distinct group of orexin neurons exhibits only transiert inhibitory responses to sustained rises in sugar levels; (h) this sensing strategy involves time-dependent recovery from inhibition via adaptive closure of leak-like K+ channels; (iii) combining transient and sustained glucosensing allows orexin cell firing to maintain sensitivity to small fluctuations in glucose levels while simultaneously encoding a large range of baseline glucose concentrations. These data provide insights into how vital behavioral orchestrators sense key features of the internal environment while susta ning a basic activity tone required for the stability of consciousness.
引用
收藏
页码:11975 / 11980
页数:6
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