Kjærby Lab

Our laboratory investigates how the arousal system regulates sleep and its role in memory consolidation and cognitive function. Sleep is shaped by slow arousal rhythms that control its phases, yet this system is highly sensitive to stress, aging, and neurodegenerative diseases. We explore how these disruptions affect sleep and memory, aiming to identify biomarkers and develop sleep-targeted therapies to improve brain health.

Infraslow oscillations of norepinephrine during sleep create pockets of spindles essential for memory consolidation. a. During NREM sleep, spindles cluster together on an infraslow time scale. Spindle density is crucial for memory consolidation during sleep. b. Using genetically encoded calcium and neuromodulator indicators, we have demonstrated that the locus coeruleus-norepinephrine system is inversely correlated with the infraslow spindle density oscillations and c. plays a causal role as demonstrated by optogenetics. d. In aging and neurodegenerative disorders, locus coeruleus is one of the first regions to degenerate and the initial hyperactivity followed by hypoactivity will affect the infraslow organization of spindles and thereby memory consolidation.

Using in vivo techniques in freely moving mice, we combine EEG/EMG-based sleep monitoring, optogenetics, and neuronal synchronization analyses with learning and memory assessments. Our research focuses on how Alzheimer’s and Parkinson’s disease—both marked by early loss of arousal-promoting neurons—impact memory consolidation during sleep. By identifying early arousal-based biomarkers, we aim to improve early diagnosis of cognitive decline.

Beyond understanding disease mechanisms, we develop therapeutic strategies to restore sleep quality and cognition through both invasive and non-invasive approaches. We also investigate the interplay between the arousal and autonomic systems to uncover new biomarkers and treatment targets. To enhance clinical translation, we collaborate with clinical researchers to align our findings with human sleep disorders and cognitive decline.

Video description of our research

Kjærby Lab webpage