scholarly journals The Interaction Between the Ventrolateral Preoptic Nucleus and the Tuberomammillary Nucleus in Regulating the Sleep-Wakefulness Cycle

2020 ◽  
Vol 14 ◽  
Author(s):  
Juan Cheng ◽  
Fang Wu ◽  
Mingrui Zhang ◽  
Ding Ding ◽  
Sumei Fan ◽  
...  
Keyword(s):  
Nrem Sleep ◽  
Sleep Time ◽  
Preoptic Nucleus ◽  
Flip Flop ◽  
Excitatory Neurotransmitter ◽  
Tuberomammillary Nucleus ◽  
Histaminergic Neurons ◽  
Electrode Recording ◽  
The Central Nervous System ◽  
Ventrolateral Preoptic Nucleus

The ventrolateral preoptic nucleus (VLPO) in the anterior hypothalamus and the tuberomammillary nucleus (TMN) in the posterior hypothalamus are critical regions which involve the regulation of sleep-wakefulness flip-flop in the central nervous system. Most of the VLPO neurons are sleep-promoting neurons, which co-express γ-aminobutyric acid (GABA) and galanin, while TMN neurons express histamine (HA), a key wake-promoting neurotransmitter. Previous studies have shown that the two regions are innervated between each other, but how to regulate the sleep-wake cycle are not yet clear. Here, bicuculline (Bic), a GABAA-receptor antagonist, L-glutamate (L-Glu), an excitatory neurotransmitter, and triprolidine (Trip), a HA1 receptor (HRH1) inhibitor, were bilaterally microinjected into TMN or VLPO after surgically implanting the electroencephalogram (EEG) and electromyography (EMG) electrode recording system. Microinjecting L-Glu into VLPO during the night significantly increased the NREM sleep time, and this phenomenon was weakened after selectively blocking GABAA receptors with Bic microinjected into TMN. Those results reveal that VLPO neurons activated, which may inhibit TMN neurons inducing sleep via GABAA receptors. On the contrary, exciting TMN neurons by L-Glu during the day, the wakefulness time was significantly increased. These phenomena were reversed by blocking HRH1 with Trip microinjected into VLPO. Those results reveal that TMN neuron activating may manipulate VLPO neurons via HRH1, and induce wakefulness. In conclusion, VLPO GABAergic neurons and TMN histaminergic neurons may interact with each other in regulating the sleep-wake cycle.

scholarly journals Chemogenetic modulation of histaminergic neurons in the tuberomammillary nucleus alters territorial aggression and wakefulness

2021 ◽  
Author(s):  
Fumito Naganuma ◽  
Tadaho Nakamura ◽  
Hiroshi Kuroyanagi ◽  
Masato Tanaka ◽  
Takeo Yoshikawa ◽  
...  
Keyword(s):  
Locomotor Activity ◽  
Nrem Sleep ◽  
Cre Recombinase ◽  
Designer Drugs ◽  
Brain Histamine ◽  
Tuberomammillary Nucleus ◽  
Territorial Aggression ◽  
Neuronal Populations ◽  
Histaminergic Neurons ◽  
Aggressive Behaviours

Abstract Designer receptor activated by designer drugs (DREADDs) techniques are widely used to modulate the activities of specific neuronal populations during behavioural tasks. However, DREADDs-induced modulation of histaminergic neurons in the tuberomammillary nucleus (HATMN neurons) has produced inconsistent effects on the sleep–wake cycle, possibly due to the use of Hdc-Cre mice driving Cre recombinase and DREADDs activity outside the targeted region. Moreover, previous DREADDs studies have not examined locomotor activity and aggressive behaviours, which are also regulated by brain histamine levels. In the present study, we investigated the effects of HATMN activation and inhibition on the locomotor activity, aggressive behaviours and sleep–wake cycle of Hdc-Cre mice with minimal non-target expression of Cre-recombinase. Chemoactivation of HATMN moderately enhanced locomotor activity in a novel open field. Activation of HATMN neurons significantly enhanced aggressive behaviour in the resident–intruder test. Wakefulness was increased and non-rapid eye movement (NREM) sleep decreased for an hour by HATMN chemoactivation. Conversely HATMN chemoinhibition decreased wakefulness and increased NREM sleep for 6 hours. These changes in wakefulness induced by HATMN modulation were related to vigilance status transition. These results indicate the influences of HATMN neurons on exploratory activity, territorial aggression, and wake maintenance.

scholarly journals Drugs affecting sleep and wakefulness: a review

2018 ◽  
Vol 7 (6) ◽  
pp. 1057 ◽  
Author(s):  
Avishek Amar
Keyword(s):  
Sleep Disturbances ◽  
Preoptic Nucleus ◽  
Hypothalamic Region ◽  
Tuberomammillary Nucleus ◽  
Social Wellbeing ◽  
Melatonin Receptor Agonists ◽  
The Common ◽  
Ventrolateral Preoptic Nucleus ◽  
Neuronal Systems ◽  
The Brain

It was in the second half of the twentieth century that Sleep Medicine was recognized as an immensely respected field of clinical research. As a result, past few decades have seen this field making some giant strides towards a better understanding of the neurochemical mechanisms that regulate the state of sleep and wakefulness. This involves a complex interplay of neuronal systems, neurotransmitters and some special nuclei located in the brain. Major wakefulness promoting nuclei being the orexinergic neurons in the lateral hypothalamic region and the tuberomammillary nucleus (TMN) while the sleep-promoting nucleus being ventrolateral preoptic nucleus (VLPO). Sleep-related complaints are one of the common complaints encountered by the physicians and the psychiatrists. As, long-standing sleep disturbances can have far-reaching implications on an individual’s physical, mental and social wellbeing, the importance of drugs affecting sleep and wakefulness could not be stressed upon anymore. Broadly, the sleep disorders are classified as insomnia, hypersomnia, and parasomnia and the presently available drugs work either by acting on the sleep-promoting GABAergic system like benzodiazepines, barbiturates etc. or by interacting with wakefulness promoting system like histaminergic system, 5- hydroxtryptaminergic system, orexinergic system etc. There are drugs which interact with other mechanisms which modulate arousal, like melatonin receptor agonists which promote sleep and adenosine receptor antagonists which promote wakefulness. This review article tries to have an overview of the available drugs for use in pathological states of sleep and wakefulness with a special emphasis on the commonly prescribed drugs and the recently approved one’s.

scholarly journals Neuropeptide S promotes wakefulness through the inhibition of sleep-promoting ventrolateral preoptic nucleus neurons

SLEEP ◽  
2019 ◽  
Vol 43 (1) ◽  
Author(s):  
Frédéric Chauveau ◽  
Damien Claverie ◽  
Emma Lardant ◽  
Christophe Varin ◽  
Eléonore Hardy ◽  
...  
Keyword(s):  
Cognitive Skills ◽  
Vascular Reactivity ◽  
Brain Slices ◽  
Nrem Sleep ◽  
Brain Structures ◽  
Gabaergic Neurons ◽  
Intraventricular Injection ◽  
Preoptic Nucleus ◽  
Neuropeptide S ◽  
Ventrolateral Preoptic Nucleus

Abstract Study Objectives The regulation of sleep-wake cycles is crucial for the brain’s health and cognitive skills. Among the various substances known to control behavioral states, intraventricular injection of neuropeptide S (NPS) has already been shown to promote wakefulness. However, the NPS signaling pathway remains elusive. In this study, we characterized the effects of NPS in the ventrolateral preoptic nucleus (VLPO) of the hypothalamus, one of the major brain structures regulating non-rapid eye movement (NREM) sleep. Methods We combined polysomnographic recordings, vascular reactivity, and patch-clamp recordings in mice VLPO to determine the NPS mode of action. Results We demonstrated that a local infusion of NPS bilaterally into the anterior hypothalamus (which includes the VLPO) significantly increases awakening and specifically decreases NREM sleep. Furthermore, we established that NPS application on acute brain slices induces strong and reversible tetrodotoxin (TTX)-sensitive constriction of blood vessels in the VLPO. This effect strongly suggests that the local neuronal network is downregulated in the presence of NPS. At the cellular level, we revealed by electrophysiological recordings and in situ hybridization that NPSR mRNAs are only expressed by non-Gal local GABAergic neurons, which are depolarized by the application of NPS. Simultaneously, we showed that NPS hyperpolarizes sleep-promoting neurons, which is associated with an increased frequency in their spontaneous IPSC inputs. Conclusion Altogether, our data reveal that NPS controls local neuronal activity in the VLPO. Following the depolarization of local GABAergic neurons, NPS indirectly provokes feed-forward inhibition onto sleep-promoting neurons, which translates into a decrease in NREM sleep to favor arousal.

Estradiol replacement enhances sleep deprivation-induced c-Fos immunoreactivity in forebrain arousal regions of ovariectomized rats

2008 ◽  
Vol 295 (4) ◽  
pp. R1328-R1340 ◽  
Author(s):  
S. Deurveilher ◽  
E. M. Cumyn ◽  
T. Peers ◽  
B. Rusak ◽  
K. Semba
Keyword(s):  
Sleep Deprivation ◽  
Body Weight Gain ◽  
Ovariectomized Rats ◽  
Adult Rats ◽  
Limbic Forebrain ◽  
Bed Nucleus ◽  
Tuberomammillary Nucleus ◽  
Female Sex Hormones ◽  
Ventrolateral Preoptic Nucleus ◽  
Oil Injection

To understand how female sex hormones influence homeostatic mechanisms of sleep, we studied the effects of estradiol (E2) replacement on c-Fos immunoreactivity in sleep/wake-regulatory brain areas after sleep deprivation (SD) in ovariectomized rats. Adult rats were ovariectomized and implanted subcutaneously with capsules containing 17β-E2 (10.5 μg; to mimic diestrous E2 levels) or oil. After 2 wk, animals with E2 capsules received a single subcutaneous injection of 17β-E2 (10 μg/kg; to achieve proestrous E2 levels) or oil; control animals with oil capsules received an oil injection. Twenty-four hours later, animals were either left undisturbed or sleep deprived by “gentle handling” for 6 h during the early light phase, and killed. E2 treatment increased serum E2 levels and uterus weights dose dependently, while attenuating body weight gain. Regardless of hormonal conditions, SD increased c-Fos immunoreactivity in all four arousal-promoting areas and four limbic and neuroendocrine nuclei studied, whereas it decreased c-Fos labeling in the sleep-promoting ventrolateral preoptic nucleus (VLPO). Low and high E2 treatments enhanced the SD-induced c-Fos immunoreactivity in the laterodorsal subnucleus of the bed nucleus of stria terminalis and the tuberomammillary nucleus, and in orexin-containing hypothalamic neurons, with no effect on the basal forebrain and locus coeruleus. The high E2 treatment decreased c-Fos labeling in the VLPO under nondeprived conditions. These results indicate that E2 replacement modulates SD-induced or spontaneous c-Fos expression in sleep/wake-regulatory and limbic forebrain nuclei. These modulatory effects of E2 replacement on neuronal activity may be, in part, responsible for E2's influence on sleep/wake behavior.

072 Sleep Spindle Harmonics in Insomnia

SLEEP ◽  
2021 ◽  
Vol 44 (Supplement_2) ◽  
pp. A29-A30
Author(s):  
Michael Goldstein ◽  
Monika Haack ◽  
Janet Mullington
Keyword(s):  
Spectral Power ◽  
Nrem Sleep ◽  
Sleep Time ◽  
Sleep Spindle ◽  
Time Frequency ◽  
Insomnia Disorder ◽  
Spectral Peaks ◽  
Limited Application ◽  
Thalamic Relay Nuclei ◽  
Restorative Sleep

Abstract Introduction Prior research has reported NREM spectral EEG differences between individuals with insomnia and good-sleeper controls, including elevated high-frequency EEG power (beta/gamma bands, ~16-50Hz) and, to a lesser extent, elevations in sleep spindle parameters. However, the mechanisms driving these differences remain unclear. Harmonics have been observed in EEG data as spectral peaks at multiples of a fundamental frequency associated with an event (e.g., for a 14Hz spindle, the 2nd harmonic is expected to be a peak at 28Hz). Thus far, there has been very limited application of this idea of spectral harmonics to sleep spindles, even though these patterns can indeed be seen in some existing literature. We sought to build on this literature to apply spectral harmonic analysis to better understand differences between insomnia and good sleepers. Methods 15 individuals with insomnia disorder (DSM-5 criteria, 13 female, age 18–32 years) and 15 good-sleeper controls (matched for sex, age, and BMI) completed an overnight polysomnography recording in the laboratory and subsequent daytime testing. Insomnia diagnosis was determined by a board-certified sleep specialist, and exclusion criteria included psychiatric history within past 6 months, other sleep disorders, significant medical conditions, and medications with significant effects on inflammation, autonomic function, or other psychotropic effects. Results Consistent with prior studies, we found elevated sleep spindle density and fast sigma power (14-16Hz). Despite no difference in beta or gamma band power when averaged across NREM sleep, time-frequency analysis centered on the peaks of detected spindles revealed a phasic elevation in spectral power surrounding the 28Hz harmonic peak in the insomnia group, especially for spindles coupled with slow waves. We also observed an overall pattern of time-locked delay in the 28Hz harmonic peak, occurring approximately 40 msec after spindle peaks. Furthermore, we observed a 42Hz ‘3rd harmonic’ peak, not yet predicted by the existing modeling work, which was also elevated for insomnia. Conclusion In conjunction with existing mathematical modeling work that has linked sleep spindle harmonic peaks with thalamic relay nuclei as the primary generators of this EEG signature, these findings may enable novel insights into specific thalamocortical mechanisms of insomnia and non-restorative sleep. Support (if any) NIH 5T32HL007901-22

250 AI-Supported Sleep Staging from Activity and Heart Rate

SLEEP ◽  
2021 ◽  
Vol 44 (Supplement_2) ◽  
pp. A101-A101
Author(s):  
Samadrita Chowdhury ◽  
TzuAn Song ◽  
Richa Saxena ◽  
Shaun Purcell ◽  
Joyita Dutta
Keyword(s):  
Heart Rate ◽  
Network Architecture ◽  
Class Imbalance ◽  
Nrem Sleep ◽  
Sleep Time ◽  
Deep Sleep ◽  
Sleep Staging ◽  
Temporal Correlations ◽  
Stage Classification ◽  
Small Form Factor

Abstract Introduction Polysomnography (PSG) is considered the gold standard for sleep staging but is labor-intensive and expensive. Wrist wearables are an alternative to PSG because of their small form factor and continuous monitoring capability. In this work, we present a scheme to perform such automated sleep staging via deep learning in the MESA cohort validated against PSG. This scheme makes use of actigraphic activity counts and two coarse heart rate measures (only mean and standard deviation for 30-s sleep epochs) to perform multi-class sleep staging. Our method outperforms existing techniques in three-stage classification (i.e., wake, NREM, and REM) and is feasible for four-stage classification (i.e., wake, light, deep, and REM). Methods Our technique uses a combined convolutional neural network coupled and sequence-to-sequence network architecture to appropriate the temporal correlations in sleep toward classification. Supervised training with PSG stage labels for each sleep epoch as the target was performed. We used data from MESA participants randomly assigned to non-overlapping training (N=608) and validation (N=200) cohorts. The under-representation of deep sleep in the data leads to class imbalance which diminishes deep sleep prediction accuracy. To specifically address the class imbalance, we use a novel loss function that is minimized in the network training phase. Results Our network leads to accuracies of 78.66% and 72.46% for three-class and four-class sleep staging respectively. Our three-stage classifier is especially accurate at measuring NREM sleep time (predicted: 4.98 ± 1.26 hrs. vs. actual: 5.08 ± 0.98 hrs. from PSG). Similarly, our four-stage classifier leads to highly accurate estimates of light sleep time (predicted: 4.33 ± 1.20 hrs. vs. actual: 4.46 ± 1.04 hrs. from PSG) and deep sleep time (predicted: 0.62 ± 0.65 hrs. vs. actual: 0.63 ± 0.59 hrs. from PSG). Lastly, we demonstrate the feasibility of our method for sleep staging from Apple Watch-derived measurements. Conclusion This work demonstrates the viability of high-accuracy, automated multi-class sleep staging from actigraphy and coarse heart rate measures that are device-agnostic and therefore well suited for extraction from smartwatches and other consumer wrist wearables. Support (if any) This work was supported in part by the NIH grant 1R21AG068890-01 and the American Association for University Women.

scholarly journals Innervation of Histaminergic Tuberomammillary Neurons by GABAergic and Galaninergic Neurons in the Ventrolateral Preoptic Nucleus of the Rat

1998 ◽  
Vol 18 (12) ◽  
pp. 4705-4721 ◽  
Author(s):  
Jonathan E. Sherin ◽  
Joel K. Elmquist ◽  
Fernando Torrealba ◽  
Clifford B. Saper
Keyword(s):  
Preoptic Nucleus ◽  
Ventrolateral Preoptic Nucleus

scholarly journals The European starling (Sturnus vulgaris) shows signs of NREM sleep homeostasis but has very little REM sleep and no REM sleep homeostasis

SLEEP ◽  
2019 ◽  
Vol 43 (6) ◽  
Author(s):  
Sjoerd J van Hasselt ◽  
Maria Rusche ◽  
Alexei L Vyssotski ◽  
Simon Verhulst ◽  
Niels C Rattenborg ◽  
...  
Keyword(s):  
Sleep Deprivation ◽  
Eye Movement ◽  
Rem Sleep ◽  
Spectral Power ◽  
Nrem Sleep ◽  
Sleep Time ◽  
European Starling ◽  
Dark Phase ◽  
Rapid Eye Movement ◽  
Sleep Homeostasis

Abstract Most of our knowledge about the regulation and function of sleep is based on studies in a restricted number of mammalian species, particularly nocturnal rodents. Hence, there is still much to learn from comparative studies in other species. Birds are interesting because they appear to share key aspects of sleep with mammals, including the presence of two different forms of sleep, i.e. non-rapid eye movement (NREM) and rapid eye movement (REM) sleep. We examined sleep architecture and sleep homeostasis in the European starling, using miniature dataloggers for electroencephalogram (EEG) recordings. Under controlled laboratory conditions with a 12:12 h light–dark cycle, the birds displayed a pronounced daily rhythm in sleep and wakefulness with most sleep occurring during the dark phase. Sleep mainly consisted of NREM sleep. In fact, the amount of REM sleep added up to only 1~2% of total sleep time. Animals were subjected to 4 or 8 h sleep deprivation to assess sleep homeostatic responses. Sleep deprivation induced changes in subsequent NREM sleep EEG spectral qualities for several hours, with increased spectral power from 1.17 Hz up to at least 25 Hz. In contrast, power below 1.17 Hz was decreased after sleep deprivation. Sleep deprivation also resulted in a small compensatory increase in NREM sleep time the next day. Changes in EEG spectral power and sleep time were largely similar after 4 and 8 h sleep deprivation. REM sleep was not noticeably compensated after sleep deprivation. In conclusion, starlings display signs of NREM sleep homeostasis but the results do not support the notion of important REM sleep functions.

Identification of histaminergic neurons in Aplysia

1990 ◽  
Vol 64 (3) ◽  
pp. 736-744 ◽  
Author(s):  
A. Elste ◽  
J. Koester ◽  
E. Shapiro ◽  
P. Panula ◽  
J. H. Schwartz
Keyword(s):  
Presynaptic Inhibition ◽  
Ganglion Cells ◽  
Lucifer Yellow ◽  
Cerebral Ganglion ◽  
Abdominal Ganglion ◽  
Serotonergic Neuron ◽  
Histaminergic Neurons ◽  
The Central Nervous System ◽  
Bag Cells ◽  
The Right

1. We have identified putative histaminergic neurons in the central nervous system of Aplysia californica by light-microscopic autoradiography after uptake of [3H]histamine and by immunohistochemistry with the use of an antibody specific for histamine. 2. In the cerebral ganglion cells previously shown to contain histamine (C2 and 2 large neighboring cells in the E cluster and a group of smaller cells in the L cluster) were identified both by uptake of [3H]histamine and by histamine immunoreactivity. The identification of C2 was confirmed by experiments in which individual C2s were characterized electrophysiologically and injected with Lucifer yellow before processing for immunohistochemistry. The giant serotonergic neuron did not take up [3H]histamine and was not immunoreactive. 3. In the abdominal ganglion two clusters of cells--one in the left hemiganglion and the other in the right--took up [3H]histamine and were histamine immunoreactive. These clusters are located in the regions occupied by the 30 identified respiratory interneurons, R25 and L25. Individual cells in the R25 and L25 clusters were identified electrophysiologically, marked by injection of Lucifer yellow, and processed for immunocytochemistry. Eleven of the 30 L25 cells examined (from 7 ganglia) and 2 of the 25 R25 cells (from 6 ganglia) that had been marked with Lucifer yellow were also histamine immunoreactive. 4. Also in the abdominal ganglion, identified cells in the L32 cluster were not histamine immunoreactive and did not take up [3H]histamine. These interneurons, which mediate presynaptic inhibition, had previously been considered histaminergic. Neurons in the ganglion known to use transmitters other than histamine (L10, R2, RB cells, and bag cells) were not histamine immunoreactive.(ABSTRACT TRUNCATED AT 250 WORDS)

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