Anaclet Lab focuses on the neurophysiology of sleep, the involvement of slow-wave sleep (SWS) in cognitive functions and the development of new interventional strategies to treat sleep-wake and circadian disorders as well as sleep loss consequences. My research combines an innovative conceptual framework for how the brain sleeps with novel, cutting-edge tools, techniques and animal models to perform this work.
The National Institutes of Health estimates that sleep-related problems affect 50 to 70 million Americans and this transcends age, gender, and socioeconomic groupings. Sleep disruption has been implicated in neuropsychiatric disorders, linked with decreased cognitive and psychomotor function and is associated with increased cancer incidence. More recent evidence has strongly implicated sleep disruption in the pathogenesis of several metabolic disorders, heart disease and obesity – all of which represent long-term targets of the Department of Health and Human Services and other public health agencies. Sleep disturbances are also thought to contribute significantly to the disease burden in many neurodegenerative disorders, including Parkinson's and Alzheimer's disease, by disrupting activity cycles and impairing cognition. Given the tremendous economic and health burden of sleep-wake, neuropsychiatric and neurodegenerative disorders, understanding the “neurocircuit” basis of sleep regulation is not only a major health priority but is central to the development of novel pharmacologic and interventional strategies. The two major ongoing areas of research in my laboratory are:
Studying the neuronal circuitry regulating the sleep-wake cycle
The sub-cortical structures regulating sleep-wake cycle and its electroencephalogram (EEG) correlates are incompletely understood. One model of sleep–wake regulation posits a “flip-flop” switching mechanism that involves mutually inhibitory interactions between sleep-promoting neurons in the ventrolateral preoptic area (VLPO) and wake-promoting neurons in the brainstem as well as the forebrain (Saper et al., Neuron 2010). With our recent discovery of the SWS-promoting parafacial zone, the field has not only gained a more accurate picture of the sleep-promoting areas of the flip-flop mechanism but also reconciled earlier findings suggesting the existence of a potent SWS-promoting/EEG synchronizing “center” in the lower brainstem of mammals.
Investigating the role of sleep in cognition
It is now generally accepted that sleep is important for normal and/or optimal cognitive function. However, the interrelationship between sleep and cognition remains incompletely understood. There is accumulating evidence suggesting that both deep sleep—otherwise known as slow-wave-sleep (SWS)—and cortical slow-wave-activity (SWA, 0.5-4 Hz) critically subserve cognitive function, in particular learning and memory. For example, SWS deprivation produces cognitive dysfunction and increased local (cortical) SWA is observed following learning tasks that link to these cortical regions. Thus far, however, the role of sleep in cognition has been studied using models of sleep deprivation that either 1) fail to discriminate the respective role of SWS and rapid-eye-movement (REM) sleep in cognition, or 2) are not designed or otherwise able to determine if increased SWS and SWA might, in fact, reverse or alleviate cognitive dysfunction. By either opto- or chemo-genetically stimulating the PZ, we have been able to exclusively promote SWS particularly enriched in SWA which we believe will permit the unprecedented ability to link (or uncouple) SWS and cortical SWA with cognition function and memory consolidation.