Neuronal stress and sleep homeostasis

We experience the restorative power of sleep every night, when we fall asleep tired and wake up more
refreshed. Insufficient and disrupted sleep has been linked to a range of neurodegenerative conditions.
However, the primary biological function of sleep remains debated. Waking activity is thought to burden basic
cellular physiology, leading to cellular stress. Extended waking and sleep disruption is associated with an
established indicator of cellular stress in neurons, which is the accumulation of misfolded proteins in the
endoplasmic reticulum lumen ("ER stress"). Indeed, sleep has been proposed to enable neurons to carry out
basic maintenance of cellular functions to prevent irreversible damage, by providing during "OFF-periods"
during which the activity of neurons is reduced. This project will, for the first time, address whether neuronal
cellular stress is an activity-dependent process that accumulates with increased neuronal activity during
waking, and whether decreased neuronal activity during sleep helps to dissipate this cellular stress. The project
will focus on the differential effects of cellular stress and recovery upon different neuronal subtypes, to
elucidate mechanisms that may underpin the regulation of sleep network patterns.