On 5 February 2014, Sebastian C. Holst who graduated as Engineer in Medicine and Technology in 2008 will be giving a seminar on Molecular mechanisms of sleep-wake regulation in healthy humans. Sebastian recently finished his PhD in Zürich and is now working as a Postdoctoral Scientist at the University of Zürich, Institute of Pharmacology and Toxicology
Join us in Bulding 349, room 214, at 1.30 pm where Sebastian will be giving a talk on the neurochemical circuitries and molecular mechanisms underlying the regulation of sleep and waking remain largely unanswered questions in modern-day neuroscience.
The striatum plays a central role in regulating movement, motivation and executive functions, and is also important for mediating arousal. Our aim was to investigate how molecular systems related to the striatum contribute to sleep-wake regulation in healthy humans.
An integrative approach was applied, investigating individual responses to sleep deprivation, functional genetic polymorphisms, molecular brain imaging, pharmacological interventions, polygraphic EEG recordings as well as cognitive performance testing, to elucidate potential underlying molecular mechanisms.
We could show that genetic differences in striatal dopaminergic neurotransmission modulate the individual response to acute sleep loss and the response to stimulants such as caffeine. Furthermore, we were able to establish that a specific subtype of glutamate receptors (mGluR5) that interacts with striatal dopaminergic neurotransmission, is increased following sleep deprivation and that this increase is linked to subjective sleepiness and distinct low-frequency brain oscillations during sleep, brain waves that hallmark human sleep need.
In summary, our findings propose a specific role for dopaminergic and glutamatergic neurotransmission in modulating human sleep-wake regulation and suggest an important role for the striatum in perturbing these findings.