Abstract
Sleep and wakefulness are greatly influenced by various physiological and psychological factors, but the neuronal elements responsible for organizing sleep-wake behavior in response to these factors are largely unknown. In this study, we report that a subset of neurons in the lateral hypothalamic area (LH) expressing the neuropeptide neurotensin (Nts) is critical for orchestrating sleep-wake responses to acute psychological and physiological challenges or stressors. We show that selective activation of NtsLH neurons with chemogenetic or optogenetic methods elicits rapid transitions from non-rapid eye movement (NREM) sleep to wakefulness and produces sustained arousal, higher locomotor activity (LMA), and hyperthermia, which are commonly observed after acute stress exposure. On the other hand, selective chemogenetic inhibition of NtsLH neurons attenuates the arousal, LMA, and body temperature (Tb) responses to a psychological stress (a novel environment) and augments the responses to a physiological stress (fasting).
Highlights
We report that a subset of neurons in the lateral hypothalamic area (LH) expressing the neuropeptide neurotensin (Nts) is critical for orchestrating sleep-wake responses to such challenges
We show that brief activation of NtsLH neurons in mice evokes immediate arousals from sleep, while their sustained activation increases wake, locomotor activity, and body temperature for several hours
As Nts neurons were found densely packed in the perifornical LH region, we examined whether these neurons co-express melanin-concentrating hormone (MCH) or orexin by immunolabelling brain sections from Nts-green fluorescent protein (GFP) mice (n = 6) for MCH and orexin
Summary
All experiments were conducted in accordance with the National Institutes of Health guidelines for the Care and Use of Laboratory Animals and were approved by the institutional. Neurotensin neurons in sleep and thermoregulation animal care and use committee of Beth Israel Deaconess Medical Center (protocol #039– 2016). All mice were group-housed in a temperature (22 ± 1 ̊C)–and humidity (40%–60%)–controlled animal room maintained on a 12:12-h light-dark cycle. All animals were singly housed for 3–4 wk before the physiological data collection began. Male mice aged 8–12 wk and weighing between 20 and 24 g at the time of surgery were used for behavioral experiments, and 4-wk-old mice were used for ex vivo brain slice recordings. We used heterozygous Nts-Cre mice on a mixed background
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