Are tuberomammillary histaminergic neurons involved in CO 2-mediated arousal?

Philip L. Johnson, Rosario Moratalla, Stafford L. Lightman, Christopher A. Lowry

Research output: Contribution to journalArticle

27 Scopus citations


An increase in arousal in response to hypercapnia [elevated arterial PCO2 (partial pressure of CO2) levels] during awake or sleep states is an important component of mechanisms designed to maintain acid-base homeostasis. Since central histaminergic neurons are crucial for maintaining waking states and vigilance, a nonresponsive or dysfunctional histaminergic system could contribute to the lack of arousal in response to hypercapnia in some sleep-related disorders [e.g., sudden infant death syndrome (SIDS) and Ondine's curse]. Therefore, the present study attempted to determine if histaminergic neurons display functional responses to acute exposure to hypercapnic gas (i.e., gas with elevated CO2 concentrations). Healthy adult male rats were placed in flow cages during the light cycle, or inactive phase, and exposed to either atmospheric air or to environmental CO2 concentrations increasing from baseline up to 20% CO2 over a 5-min period. The expression of the protein product of the immediate-early gene c-fos was used as a measure of functional cellular responses within subpopulations of histaminergic neurons. Among the histaminergic subgroups (E1-E5), only the ventral tuberommamillary nucleus (VTMn)/E2 cell group showed significant increases in c-Fos expression following brief exposure to hypercapnic gas. These data are consistent with the hypothesis that histaminergic neuronal cell groups are heterogeneous and are involved in physiological and/or behavioral responses to acute hypercapnic challenge, potentially increasing vigilance during active waking and awakening from sleep during hypercapnic states.

Original languageEnglish (US)
Pages (from-to)228-233
Number of pages6
JournalExperimental Neurology
Issue number1
StatePublished - May 2005
Externally publishedYes

ASJC Scopus subject areas

  • Neurology
  • Developmental Neuroscience

Fingerprint Dive into the research topics of 'Are tuberomammillary histaminergic neurons involved in CO <sub>2</sub>-mediated arousal?'. Together they form a unique fingerprint.

  • Cite this