ABSTRACT
Neuropeptide S (NPS) was postulated to be a wake-promoting neuropeptide with unknown mechanism, and a mutation in its receptor (NPSR1) causes the short sleep duration trait in humans. We investigated the role of different NPS+ nuclei in sleep/wake regulation. Loss-of-function and chemogenetic studies revealed that NPS+ neurons in the parabrachial nucleus (PB) are wake-promoting, whereas peri-locus coeruleus (peri-LC) NPS+ neurons are not important for sleep/wake modulation. Further, we found that a NPS+ nucleus in the central gray of the pons (CGPn) strongly promotes sleep. Fiber photometry recordings showed that NPS+ neurons are wake-active in the CGPn and wake/REM-sleep active in the PB and peri-LC. Blocking NPS-NPSR1 signaling or knockdown of Nps supported the function of the NPS-NPSR1 pathway in sleep/wake regulation. Together, these results reveal that NPS and NPS+ neurons play dichotomous roles in sleep/wake regulation at both the molecular and circuit levels.
Subject(s)
Neuropeptides , Sleep , Humans , Sleep/physiology , Pons/physiology , Locus Coeruleus/physiology , Neurons/metabolism , Neuropeptides/metabolism , Receptors, G-Protein-Coupled/metabolismABSTRACT
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.
Subject(s)
Sleep , Tegmentum Mesencephali , Wakefulness , Animals , Humans , Hypothalamic Area, Lateral/physiology , Mice , Neurons/physiology , Sleep/physiology , Tegmentum Mesencephali/physiology , Wakefulness/physiologyABSTRACT
Sleep regulation has a strong genetic component. In this review, we highlight the recent advances in sleep genetics from knockout, point mutation, and GWAS studies. We overview specific genetic effects on REM versus NREM sleep as well as how the implicated genes fall in broad functional categories. Furthermore, we elucidate how genes affect different aspects of sleep including sleep duration, sleep consolidation, recovery sleep, and the circadian timing of sleep, demonstrating that genetic studies can be powerful in understanding how the body regulates sleep.
Subject(s)
Sleep, REM , Sleep , Circadian Rhythm/genetics , Electroencephalography , Sleep/geneticsABSTRACT
SUMMARY: This note describes nTracer, an ImageJ plug-in for user-guided, semi-automated tracing of multispectral fluorescent tissue samples. This approach allows for rapid and accurate reconstruction of whole cell morphology of large neuronal populations in densely labeled brains. AVAILABILITY AND IMPLEMENTATION: nTracer was written as a plug-in for the open source image processing software ImageJ. The software, instructional documentation, tutorial videos, sample image and sample tracing results are available at https://www.cai-lab.org/ntracer-tutorial. SUPPLEMENTARY INFORMATION: Supplementary data are available at Bioinformatics online.
Subject(s)
Software , Animals , Brain , Documentation , Image Processing, Computer-Assisted , Mice , NeuronsABSTRACT
Drug-induced spoliation of hydrogels as contact lenses or as implants in the anterior eye is a frequent occurrence in clinical practice. This study explores the capacity of three commercial multipurpose solutions for contact lens care to reduce the spoliation of poly(2-hydroxyethyl methacrylate) (PHEMA) specimens exposed to a simulated aqueous humour formulation and to three topical drugs commonly administered after insertion of artificial corneas (Predsol, Optimol and Depo-Ralovera). ReNu MultiPlus (Bausch & Lomb), Complete Blink-N-Cleantrade mark Lens Drops (Allergan) and Complete Protein Remover Tablets dissolved in Complete ComfortPLUS (both from Allergan) were evaluated. All multipurpose solutions were able to dislodge passively the deposits formed on hydrogels in the simulated aqueous and in the presence of Predsol and Optimol, but none were effective against the deposits induced by Depo-Ralovera. A reduction of the calcium content in deposits caused by Predsol and Optimol was confirmed after treatment with the protein remover preparation, while the other multipurpose solutions caused the complete removal of the deposits. In experiments designed to evaluate the preventive action of the multipurpose solutions, no such effects were observed regardless of the drug involved. The prospect of using multipurpose solutions as eye drops following implantation of a hydrogel artificial cornea is a valid alternative for reducing device spoliation, however it appears to depend on the nature of the postoperative medication.
