MAPPING BRAIN CIRCUITS VULNERABLE TO CHRONIC SLEEP FRAGMENTATION IN MICE

Disrupted sleep is a common condition associated with fatigue and reduced cognitive function, while also representing a major risk factor for the development of psychiatric disorders, such as anxiety disorders. In addition to being a risk factor, disrupted sleep is also a core symptom of anxiety disorders, thereby establishing a bidirectional relationship between sleep and anxiety. It is therefore crucial to understand the underlying mechanisms of this relationship and develop targeted interventions. To investigate the neural mechanisms underlying sleep disruption, we established a chronic sleep fragmentation (SF) paradigm in mice, using specialized cages equipped with a sweeper bar that moves across the cage floor every two minutes, therefore disrupting sleep continuity. The sleep fragmentation paradigm continued for 14 consecutive days, during the light period, the habitual sleeping period of the mice. Based on electroencephalographic (EEG) recordings, we determined that this paradigm primarily disrupts REM sleep. We then assessed SF-induced changes in brain connectivity using functional ultrasound imaging. Specifically, we performed longitudinal resting-state functional ultrasound imaging before and after SF exposure, in both male and female mice. Our preliminary results reveal altered brain connectivity in SF animals, particularly within and between regions part of the triple-network system of the mouse, consisting of the default mode, salience, and lateral cortical networks. These networks are involved in emotional and memory processing, integration of internal and external stimuli, and goal-directed behavior. Our findings therefore suggest that such networks are especially vulnerable to sleep disruption and may contribute to the development of anxiety disorders.