The locus coeruleus, a pivotal region of the brain, plays a crucial role in orchestrating our mental processing and serves as the primary source of noradrenaline, a neurotransmitter that regulates arousal states and adaptive behavior. Researchers at the University of Lausanne (UNIL) have made a groundbreaking discovery, shedding new light on the locus coeruleus’s function in sleep and its disruptions, which has significant implications for our understanding of sleep disorders.
According to the study, led by Dr. Anita Lüthi, a researcher at the department of fundamental neurosciences at the faculty of biology and medicine at UNIL, “The noradrenergic locus coeruleus (LC) regulates arousal levels during wakefulness, but its role in sleep remains unclear, and our research reveals that fluctuating LC neuronal activity partitions non-rapid-eye-movement sleep (NREMS) into two distinct brain-autonomic states.” These states govern the NREMS-REM cycle over periods of approximately 50 seconds, with high LC activity inducing a subcortical-autonomic arousal state that facilitates cortical microarousals, and low LC activity facilitating NREMS-to-REMS transitions.
The study demonstrates that the locus coeruleus determines the optimal timing for transitions between the two sleep states, indicating that this brain area is essential for maintaining the normal cyclicity of sleep states. Furthermore, the researchers found that daytime experiences, particularly stress, disrupt the activity of the locus coeruleus during sleep, resulting in a disorganized sleep cycle and frequent awakenings, which can have significant consequences for overall health and well-being.
The locus coeruleus, long recognized as the primary center of noradrenaline production, which governs our ability to respond to environmental challenges by mobilizing the brain and body, is essential for cognitive wakefulness. During sleep, its activity alternates between peaks and troughs at approximately 50-second intervals, and the UNIL neuroscientists have elucidated the role of this activity, finding that both peaks and troughs play critical roles in sleep organization, functioning as a sort of internal clock.
Under normal conditions, human non-rapid-eye-movement (NREM) sleep consists of four distinct stages, including the deepest stages of sleep, while REM sleep is characterized by high brain activity associated with dreams and occupies around a quarter of the night. A typical night alternates between NREM and REM states in a coordinated manner, allowing the body and mind to rest and recover. The UNIL neuroscientists have identified the locus coeruleus as the gatekeeper of these transitions, precisely controlling when the shift from NREM to REM sleep can occur.
These discoveries have far-reaching implications for our understanding of sleep disorders and may lead to improved treatments, as Dr. Lüthi noted, “Our findings can help us better comprehend sleep disturbances associated with mental health disorders such as anxiety or other sleep disorders, and offer avenues for new treatments, like using the locus coeruleus as a biomarker to monitor and potentially correct sleep cycles.” Clinical collaborations with the Lausanne University Hospital (CHUV) have been initiated to assess whether the mechanisms identified in mice can be applied to human sleep.
