Investigations of the links between locus coeruleus and basal forebrain activity during an oddball auditory task and characteristics of sleep spindles

Abstract

This master thesis entitled “Investigation of the links between locus coeruleus and basal forebrain activity during oddball auditory task and characteristics of sleep spindles” written by Emilie Seret has been realized during academic year 2024-2025 in the GIGA-CRC In Vivo Imaging laboratory in Gilles Vandewalle’s team, promoter of this master thesis. This work aims to highlight potential links between sleep spindles and two brain regions of interest, the locus coeruleus (LC) and the basal forebrain (BF). Sleep spindles represent brief bursts of 11-16 Hz lasting < 1 to 3 seconds, occurring during N2 and N3 stages of slow waves sleep, as a result of thalamic reticular nucleus activity (TRN). This nucleus is innervated by several brain regions, among which the LC and the BF, which exert inhibitory effects on TRN neurons. 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 spindle 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 spindle 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 92 individuals of both sexes aged 18 to 75y (38.6±19.8; 61 women), including structural approaches to isolate the LC and the BF, on top of the functional MRI recording. The analyses first suggested an age-related decrease in the number and density of spindles and confirmed a higher number and density of spindles in women compared to men. Importantly analyses further reveal that a higher response of the LC during the task is significantly and positively associated with the number and density of spindles, with a stronger link in men, while no significant interactions with age were detected. Likewise, the analyses did not yield any significant association between LC activity and spindle spectral power, as well as between cholinergic BF activity and spindle characteristics, potentially due to the limited number of participants that could be included in the analyses. The findings suggest that LC activity during wakefulness may favor sleep spindle in men, potentially through 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.