Locus coeruleus activity is positively associated with spindles number in men

Sleep supports cognition, physiology, and brain plasticity through distinct oscillatory activities, including sleep spindles. They represent brief bursts of 11-16 Hz lasting <1 to 3 seconds, occurring during N2 and N3 stages of slow wave sleep. This oscillation is the result of the intrinsic activity of thalamic reticular nucleus, a sheet of GABAergic neurons enveloping parts of the thalamus. The TRN is innervated by several brain regions, among which the locus coeruleus (LC), and the basal forebrain (BF). Both have inhibitory effects on TRN neurons, the LC through noradrenergic projections, and the BF through cholinergic projections. Both the LC and BF may underlie part of the reported age- and sex-related differences in sleep spindle characteristics. Most of what is known about spindles regulation stems, however, from animal research. The translation to humans is incomplete, despite the increasing number of studies allowed by technological advancements in neuroscience, including high resolution 7 Tesla Magnetic Resonance Imaging.
This cross-sectional study aims to investigate the potential links between spindles characteristics (their number, density and spectral power) and the activity of the LC and the cholinergic BF assessed during a cognitive task. Data were collected using 7T MRI in 71 individuals of both sexes aged 18 to 75y (37.3±19.5; 52 women), including structural approaches geared towards the isolation of the LC and BF, on top of the functional MRI recording.
The analyses first suggested an age-related decrease in the number and density of spindle (p>0.05) and confirmed a higher number and density of spindles in women compared to men (p=0.002; p=0.012). Importantly analyses further of reveal that a higher response of the LC during the task is significantly and positively associated with the number and density of spindles (p=0.010; p=0.040), with a stronger link in men (p=0.013; p=0.046), while no significant interactions with age were detected (p>0.05) Likewise, the analyses did not yield any significant association between LC activity and spindle spectral power were detected (p>0.05). Similarly, no significant associations were detected between cholinergic BF response during the cognitive task and spindles characteristic (p>0.05), potentially due to the limited number of participants that could be included in the analyses.
The finding suggests that LC activity during wakefulness may favor sleep spindle in men, potentially though sex-specific LC-TRN interactions. The results may have implications for the understanding of sex differences in the prevalence of certain brain disorders to which sleep is considered to contribute.