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An excitatory peri-tegmental reticular nucleus circuit for wake maintenance.


ABSTRACT: Sleep is a necessity for our survival, but its regulation remains incompletely understood. Here, we used a human sleep duration gene to identify a population of cells in the peri-tegmental reticular nucleus (pTRNADRB1) that regulate sleep-wake, uncovering a role for a poorly understood brain area. Although initial ablation in mice led to increased wakefulness, further validation revealed that pTRNADRB1 neuron stimulation strongly promotes wakefulness, even after stimulation offset. Using combinatorial genetics, we found that excitatory pTRNADRB1 neurons promote wakefulness. pTRN neurons can be characterized as anterior- or posterior-projecting neurons based on multiplexed analysis of projections by sequencing (MAPseq) analysis. Finally, we found that pTRNADRB1 neurons promote wakefulness, in part, through projections to the lateral hypothalamus. Thus, human genetic information from a human sleep trait allowed us to identify a role for the pTRN in sleep-wake regulation.

SUBMITTER: Webb JM 

PROVIDER: S-EPMC9407645 | biostudies-literature | 2022 Aug

REPOSITORIES: biostudies-literature

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An excitatory peri-tegmental reticular nucleus circuit for wake maintenance.

Webb John M JM   Ma Mingyang M   Yin Chen C   Ptáček Louis J LJ   Fu Ying-Hui YH  

Proceedings of the National Academy of Sciences of the United States of America 20220728 34


Sleep is a necessity for our survival, but its regulation remains incompletely understood. Here, we used a human sleep duration gene to identify a population of cells in the peri-tegmental reticular nucleus (pTRN<sup>ADRB1</sup>) that regulate sleep-wake, uncovering a role for a poorly understood brain area. Although initial ablation in mice led to increased wakefulness, further validation revealed that pTRN<sup>ADRB1</sup> neuron stimulation strongly promotes wakefulness, even after stimulation  ...[more]

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