Barchi Library, 140 John Morgan Building
Department of Neuroscience
University of Pennsylvania
Dissection of preoptic sleep control circuit
In humans and other mammalian species, lesions in the preoptic area of the hypothalamus cause profound sleep impairment, indicating a crucial role of the preoptic area in sleep generation. However, the underlying circuit mechanism remains poorly understood. The sleep-active neurons are spatially intermingled with wake-active neurons, making it difficult to target the sleep neurons specifically for circuit analysis. I identified a population of preoptic area sleep neurons on the basis of their projection target and discovered their molecular markers. Using bidirectional optogenetic manipulation and optrode recording, I showed that the preoptic area GABAergic neurons projecting to the tuberomammillary nucleus are both sleep active and sleep promoting. Furthermore, using translating ribosome affinity purification and single-cell RNA sequencing I identified candidate markers for these neurons, and optogenetic and pharmacogenetic manipulations demonstrate that several peptide markers (cholecystokinin, corticotropin-releasing hormone, and tachykinin 1) label sleep-promoting neurons. Together, these findings provide easy genetic access to sleep-promoting preoptic area neurons and a valuable entry point for dissecting the sleep control circuit.
A pizza lunch will be served.