An excitatory peri-tegmental reticular nucleus circuit for wake maintenance

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 peritegmental reticular nucleus (pTRNADRB1) that regulate sleep–wake, uncovering a role for a poorly understood brain area. Al...

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Bibliographic Details
Published in:Proceedings of the National Academy of Sciences - PNAS 2022-08, Vol.119 (34), p.1-11
Main Authors: Webb, John M., Ma, Mingyang, Yin, Chen, Ptáček, Louis J., Fu, Ying-Hui
Format: Article
Language:English
Subjects:
Ablation
Animals
Biological Sciences
Circuits
Combinatorial analysis
Genetics
Humans
Hypothalamic Area, Lateral - physiology
Hypothalamus
Hypothalamus (lateral)
INAUGURAL ARTICLE
Mice
Neurons
Neurons - physiology
Sleep
Sleep - physiology
Sleep and wakefulness
Stimulation
Tegmentum Mesencephali - physiology
Wakefulness
Wakefulness - physiology
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Summary: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 peritegmental 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.
ISSN:0027-8424
1091-6490
1091-6490
DOI:10.1073/pnas.2203266119