Arousal from sleep produced by optogenetic stimulation of C1 neurons is reduced following sleep deprivation or hypoxia, but restored with systemic adenosine 1A antagonism (1178.11)

Abstract

Arousal from sleep is the major defense mechanism against asphyxia and is sensitive to environmental stressors. Here we determined whether sleep deprivation or hypoxia reduces the probability of arousal from sleep and cardiorespiratory activation by optogenetic stimulation of C1 neurons in freely‐behaving rats. Channelrhodopsin‐2 was selectively introduced into C1 neurons of Tyrosine Hydroxylase Cre‐driver rats with 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. During non‐rapid eye movement sleep, unilateral photostimulation of C1 neurons produced arousal in 86 ± 5% of trials and sighs in 65 ± 7% of trials (n=5). After sleep restriction (6am ‐ 12am), incidence of arousal and sighs were significantly reduced to 37 ± 3% and 28 ± 2% (n=4), respectively, though cardiorespiratory responses remained unchanged. A hypoxic insult (12% O2 for 30min) also reduced arousals and sigh in subsequent trials to 28 ± 4% and 18 ± 6%, respectively (n=5), but caused no change in cardiorespiratory activation. The impaired arousal and sigh incidence in both stressor models were fully restored with an adenosine 1A receptor blocker (DPCPX; 0.2 mg/kg ip), suggesting that an increase in adenosine inhibitory tone selectively depresses the wake‐promoting responses to C1 neuronal activation.Grant Funding Source: Supported by NIH (HL28785, HL74011)