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Proc Natl Acad Sci U S A. 2008 Aug 19;105(33):11975-80. doi: 10.1073/pnas.0802687105. Epub 2008 Aug 11.

Adaptive sugar sensors in hypothalamic feeding circuits.

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Department of Pharmacology, University of Cambridge, Cambridge C82 1PD, United Kingdom.


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 transient inhibitory responses to sustained rises in sugar levels; (ii) 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 sustaining a basic activity tone required for the stability of consciousness.

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