Sleep and Circadian Rhythms
Many of the individual laboratories in our department work on various
aspects of sleep and circadian rhythms, from very basic work in animals to
human clinical studies. These include laboratories run by Drs.
The basic science components
of this program use a combination of cutting edge genetic and systems
neuroscience techniques to dissect the circuitry within the brain that
regulates wake-sleep cycles and circadian rhythms. Some of our areas of
Basic sleep circuitry.
Our laboratories have pioneered the development of a flip-flop model to
explain many of the observed phenomena seen in switching from wakefulness
to NREM sleep and between NREM and REM sleep. Current studies involve the
use of conditional genetic constructs and viral vectors to allow us to
manipulate the genes for neurotransmitters and receptors in these circuits.
Other experiments use optogenetics or artificial ligand-gated ion channels
to turn genetically defined populations of neurons on or off to examine
their role in wake-sleep regulation. (Saper, Lu, Arrigoni, Fuller,
People with narcolepsy have chronic sleepiness, and episodes of muscular
weakness or paralysis known as cataplexy, due to loss of orexin (or
hypocretin) neurons in the lateral hypothalamus that produce narcolepsy. We
are using conditional knockin mice for the orexin receptors to study the
brain pathways that produce the different components of narcolepsy in mice.
In addition, we are studying the brains of people with narcolepsy and
investigating whether people with narcolepsy have abnormalities in appetite
or metabolism. (Scammell, Saper)
The suprachiasmatic nucleus (SCN) in the hypothalamus imposes a 24 hour
rhythm on nearly all biological functions, including wake-sleep, feeding,
body temperature, and locomotor activity. We explore the brain circuitry by
which the SCN imposes that influence. To do this, we use viral vectors in
genetically engineered mice to manipulate clock genes as well as genes for
neurotransmitters or receptors involved in these circuits, and measure
circadian rhythms of a variety of physiological processes. (Saper, Fuller)
Sleep and breathing.
Many people develop obstructive sleep apnea, a condition in which they stop
breathing periodically when asleep, due to collapse of their airway. We use
transgenic mice to manipulate the neurons involved in regulation of
breathing and arousal responses to hypoxia/hypercarbia, to study the brain
circuits that regulate airway patency, respiratory drive, and the
behavioral and cardiovascular consequences of repeated arousals during
sleep. (Chamberlin, Saper)
The clinical components
of this work target both the basic science of sleep-wake control and the
effects of sleep loss on pain perception and inflammation.
Human sleep circuitry and genetics.
We receive the brains from subjects in a longitudinal study of elderly
individuals, whose wake-sleep behavior was characterized by actigraphic
recording of activity. We then examine those brains for the integrity of
the wake-sleep and circadian circuitry. These subjects also donate their
DNA for study, and all have been genotyped using a 900K SNP chip, thus
allowing rapid screening of genotypes that produce specific wake-sleep or
circadian phenotypes. (Saper)
Effects of sleep and circadian rhythms on metabolism, inflammation, pain,
and cardiovascular response.
We study human subjects who undergo sleep or circadian manipulation, and
examine the effects of such disruptions on response to inflammation,
glucose metabolism, response to painful stimuli, and vascular reactivity.
Sleep Disorder Treatment