Details

Autor(en) / Beteiligte

• Williams, Rhîannan H
• Jensen, Lise T
• Verkhratsky, Alex
• Fugger, Lars
• Burdakov, Denis

Titel

Control of hypothalamic orexin neurons by acid and CO2

Ist Teil von

• Proceedings of the National Academy of Sciences - PNAS, 2007-06, Vol.104 (25), p.10685-10690

Ort / Verlag

United States: National Acad Sciences

Erscheinungsjahr

2007

Quelle

MEDLINE

Beschreibungen/Notizen

• Hypothalamic orexin/hypocretin neurons recently emerged as key orchestrators of brain states and adaptive behaviors. They are critical for normal stimulation of wakefulness and breathing: Orexin loss causes narcolepsy and compromises vital ventilatory adaptations. However, it is unclear how orexin neurons generate appropriate adjustments in their activity during changes in physiological circumstances. Extracellular levels of acid and CO 2 are fundamental physicochemical signals controlling wakefulness and breathing, but their effects on the firing of orexin neurons are unknown. Here we show that the spontaneous firing rate of identified orexin neurons is profoundly affected by physiological fluctuations in ambient levels of H + and CO 2 . These responses resemble those of known chemosensory neurons both qualitatively (acidification is excitatory, alkalinization is inhibitory) and quantitatively (≈100% change in firing rate per 0.1 unit change in pH e ). Evoked firing of orexin cells is similarly modified by physiologically relevant changes in pH e : Acidification increases intrinsic excitability, whereas alkalinization depresses it. The effects of pH e involve acid-induced closure of leak-like K + channels in the orexin cell membrane. These results suggest a new mechanism of how orexin/hypocretin networks generate homeostatically appropriate firing patterns. arousal hypocretin hypothalamus pH breathing