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Acid-sensing hypothalamic neurons controlling arousal.

Anna Kernder1, Roberto De Luca, Yevgenij Yanovsky

  • 1Department of Neurophysiology, Molecular Neurophysiology, Medical Faculty, Heinrich-Heine University, 40225, Duesseldorf, Germany.

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|May 7, 2014
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Summary
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Central nervous system pH and CO2 levels regulate breathing and vigilance. Hypothalamic hypocretin/orexin (Hcrt/Orx) and histamine (HA) neurons are excited by acidosis, promoting wakefulness and arousal.

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Area of Science:

  • Neuroscience
  • Physiology
  • Sleep Science

Background:

  • Breathing and vigilance are centrally regulated by pH and CO2.
  • Hypothalamic hypocretin/orexin (Hcrt/Orx) and histamine (HA) neurons are key wake-promoting systems.
  • Acidosis typically inhibits neuronal firing, but specific hypothalamic groups are activated.

Purpose of the Study:

  • To investigate the role of hypothalamic Hcrt/Orx and HA neurons in CO2/acid-induced arousal.
  • To elucidate the molecular mechanisms underlying proton-induced excitation of these wake-promoting neurons.

Main Methods:

  • Utilized c-Fos assays to detect neuronal activation in response to hypercapnia.
  • Performed patch-clamp recordings in rodent brain slices to assess neuronal responses to acidification.
  • Investigated molecular mechanisms including ion channels and receptors in hypothalamic neurons.

Main Results:

  • Hcrt/Orx and HA neurons in the caudal hypothalamus are excited by hypercapnia and physiological acidification (pH 7.4 to 7.0).
  • Proton-induced excitation in HA neurons involves acid-sensing ion channels, Na(+),K(+)-ATPase, and group I metabotropic glutamate receptors (mGluRI).
  • Hcrt/Orx neurons are excited via potassium conductance block, releasing glutamate and peptides.

Conclusions:

  • Hypothalamic Hcrt/Orx and HA neurons, along with the dorsal raphe nucleus, cooperate in CO2/acid-induced arousal.
  • Understanding these H(+)/CO2 activation mechanisms is crucial for treating sleep-waking disorders like sleep apnea and SIDS.