Control of hypothalamic orexin neurons by acid and CO2.
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 n...
| Үндсэн зохиолчид: | , , , , |
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| Формат: | Journal article |
| Хэл сонгох: | English |
| Хэвлэсэн: |
2007
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| _version_ | 1826274064716529664 |
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| author | Williams, R Jensen, LT Verkhratsky, A Fugger, L Burdakov, D |
| author_facet | Williams, R Jensen, LT Verkhratsky, A Fugger, L Burdakov, D |
| author_sort | Williams, R |
| collection | OXFORD |
| description | 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 CO2 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 CO2. These responses resemble those of known chemosensory neurons both qualitatively (acidification is excitatory, alkalinization is inhibitory) and quantitatively (approximately 100% change in firing rate per 0.1 unit change in pHe). Evoked firing of orexin cells is similarly modified by physiologically relevant changes in pHe: Acidification increases intrinsic excitability, whereas alkalinization depresses it. The effects of pHe 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. |
| first_indexed | 2024-03-06T22:37:46Z |
| format | Journal article |
| id | oxford-uuid:5a8458d1-73d5-49ae-8191-c7f56ecd2308 |
| institution | University of Oxford |
| language | English |
| last_indexed | 2024-03-06T22:37:46Z |
| publishDate | 2007 |
| record_format | dspace |
| spelling | oxford-uuid:5a8458d1-73d5-49ae-8191-c7f56ecd23082022-03-26T17:16:12ZControl of hypothalamic orexin neurons by acid and CO2.Journal articlehttp://purl.org/coar/resource_type/c_dcae04bcuuid:5a8458d1-73d5-49ae-8191-c7f56ecd2308EnglishSymplectic Elements at Oxford2007Williams, RJensen, LTVerkhratsky, AFugger, LBurdakov, DHypothalamic 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 CO2 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 CO2. These responses resemble those of known chemosensory neurons both qualitatively (acidification is excitatory, alkalinization is inhibitory) and quantitatively (approximately 100% change in firing rate per 0.1 unit change in pHe). Evoked firing of orexin cells is similarly modified by physiologically relevant changes in pHe: Acidification increases intrinsic excitability, whereas alkalinization depresses it. The effects of pHe 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. |
| spellingShingle | Williams, R Jensen, LT Verkhratsky, A Fugger, L Burdakov, D Control of hypothalamic orexin neurons by acid and CO2. |
| title | Control of hypothalamic orexin neurons by acid and CO2. |
| title_full | Control of hypothalamic orexin neurons by acid and CO2. |
| title_fullStr | Control of hypothalamic orexin neurons by acid and CO2. |
| title_full_unstemmed | Control of hypothalamic orexin neurons by acid and CO2. |
| title_short | Control of hypothalamic orexin neurons by acid and CO2. |
| title_sort | control of hypothalamic orexin neurons by acid and co2 |
| work_keys_str_mv | AT williamsr controlofhypothalamicorexinneuronsbyacidandco2 AT jensenlt controlofhypothalamicorexinneuronsbyacidandco2 AT verkhratskya controlofhypothalamicorexinneuronsbyacidandco2 AT fuggerl controlofhypothalamicorexinneuronsbyacidandco2 AT burdakovd controlofhypothalamicorexinneuronsbyacidandco2 |