Developmental emergence of power-law wake behavior depends upon the functional integrity of the locus coeruleus

Abstract

Study objectives: Daily amounts of sleep and wakefulness are accumulated in discrete bouts that exhibit distinct statistical properties. In adult mammals, sleep bout durations follow an exponential distribution whereas wake bout durations follow a power-law distribution. In infant Norway rats, however, wake bouts initially follow an exponential distribution and only transition to a power-law distribution beginning around postnatal day 15 (P15). Here we test the hypothesis that the locus coeruleus (LC), one of several wake-active nuclei in the brainstem, contributes to this developmental transition.

Design: At P7, rats were injected subcutaneously with saline or DSP-4, a neurotoxin that targets noradrenergic (NA) LC terminals. Then, at P21, sleep and wakefulness during the day and night were monitored. The effectiveness of DSP-4 treatment was verified by measuring NA, dopamine (DA), and serotonin (5-HT) concentration in cortical and non-cortical tissue using high performance liquid chromatography.

Results: In relation to controls, subjects treated with DSP-4 exhibited significant reductions only in cortical and non-cortical NA concentration. Consistent with our hypothesis, the wake bout durations of DSP-4 subjects more closely followed an exponential distribution, whereas those of control subjects followed the expected power-law distribution. Sleep bout distributions were unaffected by DSP-4.

Conclusions: These results suggest that the fundamental developmental transition in the statistical structure of wake bout durations is effected in part by changes in noradrenergic LC functioning. Considered within the domain of network theory, the hub-like connectivity of the LC may have important implications for the maintenance of network function in the face of random or targeted neural degeneration.

Figure 1

Log-survivor plots of sleep (A) and wake (B) bout durations in P21 rats treated with DSP-4 or saline. Each semi-log plot was constructed using pooled data (677-1180 data points). Straight lines on these plots indicate that the data follow an exponential distribution.

Figure 2

Values of r² using regression analysis of sleep (A) and wake (B) bout durations in DSP-4 and saline control P21 subjects. Sleep bout durations are better fit by exponential distributions during the day and night in subjects treated with DSP-4 or saline. Wake bout durations are better fit by power-law distributions in saline control subjects during the day and night. In contrast, wake bout durations in DSP-4 subjects are fit better by neither a power-law nor exponential distribution during the day, but are better fit by an exponential distribution at night. *significant difference between exponential and power-law fits.