Arousal from sleep by optogenetic stimulation of C1 neurons is reduced following sleep deprivation or hypoxia, but restored with systemic adenosine 1A antagonism

Peter Burke, Ruth L. Stornetta, Patrice G. Guyenet

Research output: Contribution to journalMeeting abstract

Abstract

Rationale: Arousal from sleep is the major defense mechanism against asphyxia and is sensitive to environmental stressors. Here we determined whether sleep deprivation, hypoxia or hypercapnia reduce the probability of arousal from sleep and cardiorespiratory activation by optogenetic stimulation of C1 neurons in freely-behaving rats.
Methods: Channelrhodopsin-2 was selectively introduced into C1 neurons of Tyrosine Hydroxylase Cre-driver ratswith a Cre-dependant viral vector. Sleep stages were identified from EEG and neck EMG recordings. Breathing was measured using whole body plethysmography and blood pressure by telemetry.
Main Results: Unilateral photostimulation of C1 neurons produced arousal from non-REM sleep in 86 ± 3% of trials and sighs in 70 ± 5% of trials (n=9). After sleep restriction (6am – 12am), arousal and sigh incidence were significantly reduced to 37 ± 3% and 28 ± 2%, respectively. After a hypoxic episode (12% O2 for 30min), arousal and sigh incidence fell to 28 ± 4% and 18 ± 4%. Pre-treatment with an adenosine 1A receptor blocker (DPCPX; 0.2 mg/kg inter-peritoneal), but not its vehicle (DMSO), prevented hypoxic-suppression of arousal and sigh incidence. Hypercapnia (3 or 6% FiCO2) or sleep (time control) did not reduce arousal/sigh incidence. Cardiorespiratory stimulation was also unchanged across all stressor paradigms.
Conclusions: Arousal by C1 stimulation is suppressed by prior hypoxia or sleep deprivation. We suspect an increase in adenosine inhibitory tone in wake-promoting loci targeted by C1 cells selectively depresses the arousal/sigh responses.
Original languageEnglish
Article number859.6
JournalFASEB Journal
Volume29
Issue number1 supplement
Publication statusPublished - Apr 2015
Externally publishedYes
EventExperimental Biology Meeting - Boston, United States
Duration: 28 Mar 20151 Apr 2015

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