Optogenetic Reverse-engineering of Brain Sleep/wake Circuitry

The neural control of sleep and wakefulness depends upon a complex and partially defined balance between subcortical excitatory and inhibitory populations in the brain. Wake-active neurons include hypocretin (Hcrt)-containing neurons in the lateral hypothalamus and noradrenergic neurons that make up the brainstem locus coeruleus (LC). Experimentally determining a causal role for these neurons in promoting and maintaining wakefulness has remained elusive using traditional pharmacological and electrical techniques due to their small size, unique morphology, and proximity to heterogeneous neuronal and non-neuronal cell types. The recent development of optogenetic technology provides a toolkit of genetically-encodable, millisecond timescale, stimulation and inhibition probes that can be targeted to specific cell types with no toxicity to the cells under investigation. This dissertation discusses the application of optogenetic tools to questions about sleep/wake circuitry and uses these tools to study Hcrt and LC neurons, both individually and in combination.