GABAA receptors in the pontine reticular formation of C57BL/6J mouse modulate neurochemical, electrographic, and behavioral phenotypes of wakefulness

Ra Shonda R. Flint, Theresa Chang, Ralph Lydic, Helen Baghdoyan

Research output: Contribution to journalArticle

24 Citations (Scopus)

Abstract

Drugs that potentiate transmission at GABAA receptors are widely used to enhance sleep and to cause general anesthesia. The mechanisms underlying these effects are unknown. This study tested the hypothesis that GABAA receptors in the pontine reticular nucleus, oral part (PnO) of mouse modulate five phenotypes of arousal: sleep and wakefulness, cortical electroencephalogram (EEG) activity, acetylcholine (ACh) release in the PnO, breathing, and recovery time from general anesthesia. Microinjections into the PnO of saline (vehicle control), the GABAA receptor agonist muscimol, muscimol with the GABAA receptor antagonist bicuculline, and bicuculline alone were performed in male C57BL/6J mice (n = 33) implanted with EEG recording electrodes. Muscimol caused a significant increase in wakefulness and decrease in rapid eye movement (REM) and non-REM (NREM) sleep. These effects were reversed by coadministration of bicuculline. Bicuculline administered alone caused a significant decrease in wakefulness and increase in NREM sleep and REM sleep. Muscimol significantly increased EEG power in the delta range (0.5-4 Hz) during wakefulness and in the theta range (4-9 Hz) during REM sleep. Dialysis delivery of bicuculline to the PnO of male mice (n = 18) anesthetized with isoflurane significantly increased ACh release in the PnO, decreased breathing rate, and increased anesthesia recovery time. All drug effects were concentration dependent. The effects on phenotypes of arousal support the conclusion that GABAA receptors in the PnO promote wakefulness and suggest that increasing GABAergic transmission in the PnO may be one mechanism underlying the phenomenon of paradoxical behavioral activation by some benzodiazepines.

Original languageEnglish (US)
Pages (from-to)12301-12309
Number of pages9
JournalJournal of Neuroscience
Volume30
Issue number37
DOIs
StatePublished - Sep 15 2010
Externally publishedYes

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Wakefulness
GABA-A Receptors
Inbred C57BL Mouse
Bicuculline
Muscimol
Sleep
Phenotype
REM Sleep
Electroencephalography
Arousal
General Anesthesia
Acetylcholine
Respiration
GABA-A Receptor Agonists
GABA-A Receptor Antagonists
Isoflurane
Microinjections
Eye Movements
Benzodiazepines
Pharmaceutical Preparations

All Science Journal Classification (ASJC) codes

  • Neuroscience(all)

Cite this

GABAA receptors in the pontine reticular formation of C57BL/6J mouse modulate neurochemical, electrographic, and behavioral phenotypes of wakefulness. / Flint, Ra Shonda R.; Chang, Theresa; Lydic, Ralph; Baghdoyan, Helen.

In: Journal of Neuroscience, Vol. 30, No. 37, 15.09.2010, p. 12301-12309.

Research output: Contribution to journalArticle

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