Hypothalamus

About: Hypothalamus is a research topic. Over the lifetime, 22301 publications have been published within this topic receiving 1085925 citations.

Identification of preoptic sleep neurons using retrograde labelling and gene profiling

Abstract: Identification of sleep-active and sleep-promoting neurons in the preoptic area of the hypothalamus using neural projection tracing tools to target this population among a group of intermingled neurons, all with various functions The preoptic area (POA) in the hypothalamus is an essential contributor to typical sleep regulation, but how this brain area is involved in this process has not been well-understood Now, Yang Dan and colleagues dissect the role of sleep-active neurons in the POA using neural-projection-tracing tools to specifically target this population of neurons amongst a group of intermingled neurons with various functions The POA sleep neurons were GABAergic and projected to the tuberomammillary nucleus and were not only active during sleep but could promote sleep when activated Further, single-cell molecular analysis provided candidate genetic markers with which to target these neurons for future studies aiming to further dissect this sleep control circuit In humans and other mammalian species, lesions in the preoptic area of the hypothalamus cause profound sleep impairment1,2,3,4,5, indicating a crucial role of the preoptic area in sleep generation However, the underlying circuit mechanism remains poorly understood Electrophysiological recordings and c-Fos immunohistochemistry have shown the existence of sleep-active neurons in the preoptic area, especially in the ventrolateral preoptic area and median preoptic nucleus6,7,8,9 Pharmacogenetic activation of c-Fos-labelled sleep-active neurons has been shown to induce sleep10 However, the sleep-active neurons are spatially intermingled with wake-active neurons6,7, making it difficult to target the sleep neurons specifically for circuit analysis Here we identify a population of preoptic area sleep neurons on the basis of their projection target and discover their molecular markers Using a lentivirus expressing channelrhodopsin-2 or a light-activated chloride channel for retrograde labelling, bidirectional optogenetic manipulation, and optrode recording, we show that the preoptic area GABAergic neurons projecting to the tuberomammillary nucleus are both sleep active and sleep promoting Furthermore, translating ribosome affinity purification and single-cell RNA sequencing identify 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