Region-Specific Dissociation between Cortical Noradrenaline Levels and the Sleep/ Wake Cycle.

STUDY OBJECTIVE: The activity of the noradrenergic system of the locus coeruleus (LC) is high in wake and low in sleep. LC promotes arousal and EEG activation, as well as attention, working memory, and cognitive flexibility. These functions rely on prefrontal cortex and are impaired by sleep deprivation, but the extent to which LC activity changes during wake remains unclear. Moreover, it is unknown whether noradrenergic neurons can sustain elevated firing during extended wake. Recent studies show that relative to LC neurons targeting primary motor cortex (M1), those projecting to medial prefrontal cortex (mPFC) have higher spontaneous firing rates and are more excitable. These results suggest that noradrenaline (NA) levels should be higher in mPFC than M1, and that during prolonged wake LC cells targeting mPFC may fatigue more. DESIGN: In vivo microdialysis to determine how cortical NA levels change during the sleep/wake cycle and in the course of sleep deprivation. SETTING: Basic sleep research laboratory. SUBJECTS: Adult (9-10 weeks old) C57-BL6 mice. INTERVENTIONS: Recordings during spontaneous sleep and wake (n = 8 mice), and sleep deprivation (n = 6). MEASUREMENTS AND RESULTS: We find that absolute NA levels are higher in mPFC than in M1. Moreover, in both areas they decline during sleep and increase during wake, but these changes are faster in M1 than mPFC. Finally, by the end of sleep deprivation NA levels decline only in mPFC. CONCLUSIONS: LC neurons targeting prefrontal cortex may fatigue more markedly, or earlier, than other LC cells, suggesting one of the mechanisms underlying the cognitive impairment and the increased sleep presure associated with sleep deprivation.