Glutamatergic neurons in the preoptic hypothalamus promote wakefulness, destabilize NREM sleep, suppress REM sleep, and regulate cortical dynamics

Mondino, Alejandra; Hambrecht-Wiedbusch, Viviane S.; Li, Duan; York, A. Kane; Pal, Dinesh; González, Joaquín; Torterolo, Pablo; Mashour, George A.; Vanini, Giancarlo

doi:10.1101/2020.10.20.347260

Cited by 11 publications

(15 citation statements)

References 96 publications

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“…Moreover, neurons in the PVN are also responsible for endocrine regulation through hormone production and release [ 64 , 65 ]. The LH, MPOA, VLPO, DMH and SPVZ regulate sleep/wakefulness, locomotion, and thermoregulation [ 63 , 66 , 67 , 68 , 69 ]. Altogether, these hypothalamic nuclei maintain organism-wide energy balance.…”

Section: Chronology Of Clocks In the Hypothalamic Nucleimentioning

confidence: 99%

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Circadian Rhythms of the Hypothalamus: From Function to Physiology

Drunen

Eckel‐Mahan

2021

Clocks & Sleep

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The nearly ubiquitous expression of endogenous 24 h oscillations known as circadian rhythms regulate the timing of physiological functions in the body. These intrinsic rhythms are sensitive to external cues, known as zeitgebers, which entrain the internal biological processes to the daily environmental changes in light, temperature, and food availability. Light directly entrains the master clock, the suprachiasmatic nucleus (SCN) which lies in the hypothalamus of the brain and is responsible for synchronizing internal rhythms. However, recent evidence underscores the importance of other hypothalamic nuclei in regulating several essential rhythmic biological functions. These extra-SCN hypothalamic nuclei also express circadian rhythms, suggesting distinct regions that oscillate either semi-autonomously or independent of SCN innervation. Concurrently, the extra-SCN hypothalamic nuclei are also sensitized to fluctuations in nutrient and hormonal signals. Thus, food intake acts as another powerful entrainer for the hypothalamic oscillators’ mediation of energy homeostasis. Ablation studies and genetic mouse models with perturbed extra-SCN hypothalamic nuclei function reveal their critical downstream involvement in an array of functions including metabolism, thermogenesis, food consumption, thirst, mood and sleep. Large epidemiological studies of individuals whose internal circadian cycle is chronically disrupted reveal that disruption of our internal clock is associated with an increased risk of obesity and several neurological diseases and disorders. In this review, we discuss the profound role of the extra-SCN hypothalamic nuclei in rhythmically regulating and coordinating body wide functions.

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Section: Chronology Of Clocks In the Hypothalamic Nucleimentioning

confidence: 99%

“…regulate sleep/wakefulness, locomotion, and thermoregulation [63,[66][67][68][69]. Altogether, these hypothalamic nuclei maintain organism-wide energy balance.…”

Section: Chronology Of Clocks In the Hypothalamic Nucleimentioning

confidence: 99%

Circadian Rhythms of the Hypothalamus: From Function to Physiology

Drunen

Eckel‐Mahan

2021

Clocks & Sleep

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“…Although most of the neurons whose activity have been related to sleep are GABAergic (Fang et al, 2018; Lonstein and De Vries, 2000; Tsuneoka et al, 2013), it has been recently showed that a subgroup of glutamatergic neurons within the mPOA promotes NREM sleep together with body cooling (Harding et al, 2018). In addition to somnogenic POA neurons, it has been recently reported a group of glutamatergic neurons within the mPOA whose chemogenetic activation increases wakefulness, and decreases both NREM and REM sleep (Mondino et al, 2021; Vanini et al, 2020). Regarding the mechanisms underlying the effects of HCRT in POA neurons, (Eggermann et al, 2001) have studied the effects of HCRT-1 perfusion in neurons of VLPO in rat brain slices.…”

Section: Discussionmentioning

confidence: 99%

“…In addition, administration of glutamate (Kaushik et al, 2011) or adenosine (Mendelson, 2000) into the mPOA, as well as the activation of GABAergic and galaninergic neurons of this area promote NREM sleep (Chung et al, 2017; Harding et al, 2018; Kroeger et al, 2018; Vanini et al, 2020). Recently, it has been reported that the chemogenetic activation of a group of glutamatergic neurons within the mPOA and surroundings areas increases wakefulness, and decreases both NREM and REM sleep (Mondino et al, 2021; Vanini et al, 2020), suggesting that mPOA contains not only sleep-inducing neurons, but also wake-promoting neurons.…”

Section: Introductionmentioning

confidence: 99%

Role of hypocretin in the medial preoptic area in the regulation of sleep, maternal behavior and body temperature of lactating rats

Rivas

Serantes

Peña

et al. 2021

Preprint

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The hypocretins (HCRT), also known as orexin, includes two neuroexcitatory peptides, HCRT-1 and HCRT-2 (orexin A y B, respectively), synthesized by neurons located in the postero-lateral hypothalamus, whose projections and receptors are widely distributed throughout the brain, including the medial preoptic area (mPOA). HCRT have been associated with a wide range of physiological functions including sleep-wake cycle, maternal behavior and body temperature, all regulated by the mPOA. Previously we showed that HCRT in the mPOA facilitates certain active maternal behaviors, while the blockade of HCRT-R1 increased the time spent in nursing. As mother rats mainly sleep while they nurse, we hypothesize that HCRT in the mPOA of lactating rats reduce sleep and nursing, while the intra-mPOA administration of the dual orexin receptor antagonist (DORA) would generate the opposite effect. Therefore, the aim of this study was to determine the role of HCRT within the mPOA, in the regulation and integration of the sleep-wake cycle, maternal behavior and body temperature of lactating rats. To evaluate this idea, we assessed the sleep-wake states, maternal behavior and body temperature of lactating rats following microinjections of HCRT-1 (100 and 200 uM) and DORA (5mM) into the mPOA. As expected, our data shows that HCRT-1 in mPOA promoted wakefulness and a slightly increase in body temperature, whereas DORA increased both NREM and REM sleep along with nursing and milk ejection. Taken together, our results strongly suggest that the reduction of the endogenous HCRT within the mPOA of lactating rats is important to promote sleep, nursing and milk ejection.

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“…In this sense, recent evidence show that the lateral preoptic area triggers awakening from sleep and that the waking state is accompanied with an increased in the cortical activity [66]. In addition, recent reports evidenced that chemogenetic stimulation of glutamatergic neurons induce wakefulness [67, 68]. Thus, it can be postulated that BIC would directly disinhibit these glutamatergic neurons that promote wakefulness.…”

Section: Discussionmentioning

confidence: 99%

Local administration of bicuculline into the ventrolateral and medial preoptic nuclei modifies sleep and maternal behavior in lactating rats

Benedetto

Rivas

Peña

et al. 2021

Preprint

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The preoptic area (POA) is a brain structure classically involved in a wide variety of animal behavior including sleep and maternal care. In the current study, we evaluate the specific effect of disinhibition of two specific regions of the POA, the medial POA nucleus (mPOA) and the ventrolateral POA area (VLPO) on sleep and maternal behavior in lactating rats. For this purpose, mother rats on postpartum day 1 (PPD1) were implanted for polysomnographic recordings and with bilateral cannulae either in the mPOA or in the VLPO. The rats were tested for sleep and maternal behavior on PPD4-8 after the infusion of the GABA-A antagonist, bicuculline (0, 10 or 30 ng/0.2 μl/side). Infusion of bicuculline into the mPOA augmented retrieving and nest building behaviors and reduced both nursing and milk ejections but had almost no effect on sleep. When bicuculine was microinjected into the VLPO, the rats significantly increase the number of retrievings and mouthings and reduced the nursing time without changes in milk ejections, which was associated with an increase in wakefulness and a reduction in light sleep. Our results show that disinhibition of the mPOA, a key area in the control of maternal behavior, increased active maternal behaviors and reduced nursing without affecting wakefulness or sleep time. In contrast, the enhancement of some active maternal behaviors when the drug was infused into the VLPO, a sleep-promoting area, with a concomitant increase in wakefulness suggests that mother rats devote this additional waking time in the active maternal care of the pups. We hypothesize that maternal behavior changes after bicuculine microinjection into the VLPO is caused by a reduction in the sleep drive, rather than a direct effect on maternal behavior.

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Glutamatergic neurons in the preoptic hypothalamus promote wakefulness, destabilize NREM sleep, suppress REM sleep, and regulate cortical dynamics

Cited by 11 publications

References 96 publications

Circadian Rhythms of the Hypothalamus: From Function to Physiology

Circadian Rhythms of the Hypothalamus: From Function to Physiology

Role of hypocretin in the medial preoptic area in the regulation of sleep, maternal behavior and body temperature of lactating rats

Local administration of bicuculline into the ventrolateral and medial preoptic nuclei modifies sleep and maternal behavior in lactating rats

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