scholarly journals “Activity of a subset of vesicular GABA-transporter neurons in the ventral zona incerta anticipate sleep onset”

SLEEP ◽  
2020 ◽  
Author(s):  
Carlos Blanco-Centurion ◽  
SiWei Luo ◽  
Aurelio Vidal-Ortiz ◽  
Colby Swank ◽  
Priyattam J Shiromani
Keyword(s):  
Lateral Hypothalamus ◽  
Sleep Onset ◽  
Nrem Sleep ◽  
Zona Incerta ◽  
Rapid Eye Movement Sleep ◽  
Gaba Transporter ◽  
Gaba Neurons ◽  
Freely Behaving ◽  
Behavioral States ◽  
Multiple Episodes

Abstract Study Objectives Sleep and wake are opposing behavioral states controlled by the activity of specific neurons that need to be located and mapped. To better understand how a waking brain falls asleep it is necessary to identify activity of individual phenotype-specific neurons, especially neurons that anticipate sleep onset. In freely-behaving mice, we used microendoscopy to monitor calcium (Ca 2+) fluorescence in individual hypothalamic neurons expressing the vesicular GABA transporter (vGAT), a validated marker of GABA neurons. Methods vGAT-Cre mice (male=3; female=2) transfected with rAAV-FLEX-GCaMP6M in the lateral hypothalamus were imaged 30 days later during multiple episodes of waking (W), non-rapid-eye movement sleep (NREMS) or REMS (REMS). Results 372 vGAT neurons were recorded in the zona incerta. 23.9% of the vGAT neurons showed maximal fluorescence during wake (classified as wake-max), 4% were NREM-max, 56.2% REM-max and 5.9% wake/REM max, while 9.9% were state indifferent. In the NREM-max group, Ca 2+ fluorescence began to increase before onset of NREM sleep, remained high throughout NREM sleep, and declined in REM sleep. Conclusions We found that 60.2% of the vGAT GABA neurons in the zona incerta had activity that was biased towards sleep (NREM and REMS). A subset of vGAT neurons (NREM-max) became active in advance of sleep onset and may induce sleep by inhibiting the activity of the arousal neurons. Abnormal activation of the NREM-max neurons may drive sleep attacks and hypersomnia.

scholarly journals Vesicular GABA-transporter neurons in the zona incerta are maximally active during non rapid-eye movement (NREM) and rapid-eye movement (REM) sleep

2020 ◽  
Author(s):  
Carlos Blanco-Centurion ◽  
SiWei Luo ◽  
Aurelio Vidal-Ortiz ◽  
Priyattam J. Shiromani
Keyword(s):  
Eye Movement ◽  
Lateral Hypothalamus ◽  
Rem Sleep ◽  
Sleep Onset ◽  
Nrem Sleep ◽  
Zona Incerta ◽  
Imaging Method ◽  
Rapid Eye Movement ◽  
Gaba Transporter

AbstractSleep and wake are opposing behavioral states controlled by the activity of specific neurons. The neurons responsible for sleep/wake control have not been fully identifed due to the lack of in-vivo high throughput technology. We use the deep-brain calcium (Ca2+) imaging method to identify activity of hypothalamic neurons expressing the vesicular GABA transporter (vGAT), a marker of GABAergic neurons. vGAT-cre mice (n=5) were microinjected with rAAV-FLEX-GCaMP6M into the lateral hypothalamus and 21d later the Ca2+ influx in vGAT neurons (n=372) was recorded in freely-behaving mice during waking (W), NREM and REM sleep. Post-mortem analysis revealed the lens tip located in the zona incerta/lateral hypothalamus (ZI-LH) and the change in fluorescence of neurons in the field of view was as follows: 54.9% of the vGAT neurons had peak fluorescence during REM sleep (REM-max), 17.2% were NREM-max, 22.8% were wake-max while 5.1% were both wake+REM max. Thus, three quarters of the recorded vGAT neurons in the ZI-LH were most active during sleep. In the NREM-max group Ca2+ fluorescence anticipated the initiation of NREM sleep onset and remained high throughout sleep (NREM and REM sleep). In the REM-max neurons Ca2+fluorescence increased before the onset of REM sleep and stayed elevated during the episode. Activation of the vGAT NREM-max neurons in the zona incerta and dorsal lateral hypothalamus would inhibit the arousal neurons to initiate and maintain sleep.

scholarly journals Rapid changes in glutamate levels in the posterior hypothalamus across sleep-wake states in freely behaving rats

2008 ◽  
Vol 295 (6) ◽  
pp. R2041-R2049 ◽  
Author(s):  
Joshi John ◽  
Lalini Ramanathan ◽  
Jerome M. Siegel
Keyword(s):  
Eye Movement ◽  
Rem Sleep ◽  
Glutamate Release ◽  
Sleep Onset ◽  
Nrem Sleep ◽  
Progressive Increase ◽  
High Temporal Resolution ◽  
Hypothalamic Region ◽  
Rapid Changes ◽  
Freely Behaving

The histamine-containing posterior hypothalamic region (PH-TMN) plays a key role in sleep-wake regulation. We investigated rapid changes in glutamate release in the PH-TMN across the sleep-wake cycle with a glutamate biosensor that allows the measurement of glutamate levels at 1- to 4-s resolution. In the PH-TMN, glutamate levels increased in active waking (AW) and rapid eye movement (REM) sleep compared with quiet waking and nonrapid eye movement (NREM) sleep. There was a rapid (0.6 ± 1.8 s) and progressive increase in glutamate levels at REM sleep onset. A reduction in glutamate levels consistently preceded the offset of REM sleep by 8 ± 3 s. Short-duration sleep deprivation resulted in a progressive increase in glutamate levels in the PH-TMN, perifornical-lateral hypothalamus (PF-LH), and cortex. We found that in the PF-LH, glutamate levels took a longer time to return to basal values compared with the time it took for glutamate levels to increase to peak values during AW onset. This is in contrast to other regions we studied in which the return to baseline values after AW was quicker than their rise with waking onset. In summary, we demonstrated an increase in glutamate levels in the PH-TMN with REM/AW onset and a drop in glutamate levels before the offset of REM. High temporal resolution measurement of glutamate levels reveals dynamic changes in release linked to the initiation and termination of REM sleep.

scholarly journals Sleep deprivation triggers somatostatin neurons in prefrontal cortex to initiate nesting and sleep via the preoptic and lateral hypothalamus

2020 ◽  
Author(s):  
Kyoko Tossell ◽  
Xiao Yu ◽  
Berta Anuncibay Soto ◽  
Mikal Vicente ◽  
Giulia Miracca ◽  
...  
Keyword(s):  
Prefrontal Cortex ◽  
Sleep Deprivation ◽  
Long Range ◽  
Lateral Hypothalamus ◽  
Nrem Sleep ◽  
Nest Building ◽  
Local Activation ◽  
Gaba Neurons ◽  
Somatostatin Neurons ◽  
Innate Behaviors

AbstractAnimals undertake specific behaviors before sleep. Little is known about whether these innate behaviors, such as nest building, are actually an intrinsic part of the sleep-inducing circuitry. We found, using activity-tagging genetics, that mouse prefrontal cortex (PFC) somatostatin/GABAergic (SOM/GABA) neurons, which become activated during sleep deprivation, induce nest building when opto-activated. These tagged neurons induce sustained global NREM sleep if their activation is prolonged metabotropically. Sleep-deprivation-tagged PFC SOM/GABA neurons have long-range projections to the lateral preoptic (LPO) and lateral hypothalamus (LH). Local activation of tagged PFC SOM/GABA terminals in LPO and the LH induced nesting and NREM sleep respectively. Our findings provide a circuit link for how the PFC responds to sleep deprivation by coordinating sleep preparatory behavior and subsequent sleep.

Two-color immunohistochemistry for dopamine and GABA neurons in rat substantia nigra and zona incerta

1982 ◽  
Vol 9 (1-6) ◽  
pp. 463-474 ◽  
Author(s):  
W.H. Oertel ◽  
M.L. Tappaz ◽  
A. Berod ◽  
E. Mugnaini
Keyword(s):  
Substantia Nigra ◽  
Zona Incerta ◽  
Gaba Neurons ◽  
Rat Substantia Nigra

scholarly journals Aging is associated with increased propensity for central apnea during NREM sleep

2018 ◽  
Vol 124 (1) ◽  
pp. 83-90 ◽  
Author(s):  
Susmita Chowdhuri ◽  
Sukanya Pranathiageswaran ◽  
Hillary Loomis-King ◽  
Anan Salloum ◽  
M. Safwan Badr
Keyword(s):  
Carbon Dioxide ◽  
Older Adults ◽  
Young Adults ◽  
Nrem Sleep ◽  
The Elderly ◽  
Central Apnea ◽  
Elderly Adults ◽  
Rapid Eye Movement Sleep ◽  
Controller Gain ◽  
Central Apneas

The reason for increased sleep-disordered breathing with predominance of central apneas in the elderly is unknown. We hypothesized that the propensity to central apneas is increased in older adults, manifested by a reduced carbon-dioxide (CO2) reserve in older compared with young adults during non-rapid eye movement sleep. Ten elderly and 15 young healthy adults underwent multiple brief trials of nasal noninvasive positive pressure ventilation during stable NREM sleep. Cessation of mechanical ventilation (MV) resulted in hypocapnic central apnea or hypopnea. The CO2 reserve was defined as the difference in end-tidal CO2 ([Formula: see text]) between eupnea and the apneic threshold, where the apneic threshold was [Formula: see text] that demarcated the central apnea closest to the eupneic [Formula: see text]. For each MV trial, the hypocapnic ventilatory response (controller gain) was measured as the change in minute ventilation (V̇e) during the MV trial for a corresponding change in [Formula: see text]. The eupneic [Formula: see text] was significantly lower in elderly vs. young adults. Compared with young adults, the elderly had a significantly reduced CO2 reserve (−2.6 ± 0.4 vs. −4.1 ± 0.4 mmHg, P = 0.01) and a higher controller gain (2.3 ± 0.2 vs. 1.4 ± 0.2 l·min−1·mmHg−1, P = 0.007), indicating increased chemoresponsiveness in the elderly. Thus elderly adults are more prone to hypocapnic central apneas owing to increased hypocapnic chemoresponsiveness during NREM sleep. NEW & NOTEWORTHY The study describes an original finding where healthy older adults compared with healthy young adults demonstrated increased breathing instability during non-rapid eye movement sleep, as suggested by a smaller carbon dioxide reserve and a higher controller gain. The findings may explain the increased propensity for central apneas in elderly adults during sleep and potentially guide the development of pathophysiology-defined personalized therapies for sleep apnea in the elderly.

851 Self-Medication with Caffeine for 31 Years: A Case of Undiagnosed Childhood Narcolepsy Type II

SLEEP ◽  
2021 ◽  
Vol 44 (Supplement_2) ◽  
pp. A331-A331
Author(s):  
Moustapha Doulaye Seydou ◽  
Christian Karime ◽  
Brenda Wyrick ◽  
Amir Khan
Keyword(s):  
Sleep Latency ◽  
Treatment Plan ◽  
Sleep Onset ◽  
Panic Attacks ◽  
Apnea Hypopnea Index ◽  
Type Ii ◽  
Obstructive Sleep ◽  
Sleep Benefit ◽  
Patient Reported ◽  
Multiple Episodes

Abstract Introduction Narcolepsy represents a relatively rare chronic neurological sleep disorder. While peak incidence occurs in adolescence and early-adulthood, reports indicate a substantial number of children under 10 remain undiagnosed or are misdiagnosed. The present case describes a female with undiagnosed narcolepsy type II self-medicating with caffeinated beverages from the age of 7. Report of case(s) A 40-year-old female presented at our clinic with excessive daytime fatigue and hypersomnolence despite adequate sleep (Epworth sleepiness scale= 16/24). The patient denied snoring, sleep paralysis, catalepsy, and hypnagogic/hypnopompic hallucinations. Symptoms began at the age of 7 and steadily worsened, with teachers reporting significant concentration difficulties and multiple episodes of unintentional sleep onset in the classroom. The patient reported heavily relying on caffeinated beverages from the age of 7 to remain awake and focused on classroom activities. Starting at the age of 7, the patient consumed on average a caffeine-equivalent of 1 espresso shot/day (64mg caffeine/day). This increased to 4–6 espresso shots/day (256-384mg caffeine/day) by the age of 12 and 5–9 espresso shots/day (320-576mg caffeine/day) by the age of 18. At the age of 25, the patient developed severe anxiety with panic attacks and episodes of suicidal ideation. With multiple episodes of sleep onset while operating a motor vehicle, a near-accident prompted medical evaluation. Diagnosed with general anxiety disorder and idiopathic hypersomnolence, escitalopram and armodafinil were started with limited effect. The patient continued self-medicating with caffeinated beverages until age 38 when she was diagnosed with narcolepsy type II. Sodium oxybate was subsequently added to her treatment plan with initial sleep benefit and caffeine reduction. A repeat mean sleep latency test confirmed narcolepsy type II (mean sleep latency= 3 minutes, mean rapid eye movement [REM] sleep latency= 3 minutes). Polysomnography was later performed due to non-resolving symptoms, revealing mild obstructive sleep apnea (REM apnea-hypopnea index= 13.5/hour). Continuous positive airway pressure was added to the treatment regime with significant sleep benefit. Conclusion We describe a case of undiagnosed childhood narcolepsy type II necessitating significant caffeine consumptions in order to maintain classroom performance. With known anxiety-provoking effects of caffeine, the case highlights the importance of addressing childhood narcolepsy. Support (if any):

scholarly journals Dream Generation and Recall in Daytime NREM Sleep of Patients With Narcolepsy Type 1

2020 ◽  
Vol 14 ◽  
Author(s):  
Carlo Cipolli ◽  
Fabio Pizza ◽  
Claudia Bellucci ◽  
Michela Mazzetti ◽  
Giovanni Tuozzi ◽  
...  
Keyword(s):  
Cognitive Processes ◽  
Rem Sleep ◽  
Healthy Subjects ◽  
Structural Organization ◽  
Sleep Onset ◽  
Negative Attitude ◽  
Nrem Sleep ◽  
The Difference ◽  
Multiple Sleep Latency

The less rigid architecture of sleep in patients with narcolepsy type 1 (NT1) compared with healthy subjects may provide new insights into some unresolved issues of dream experience (DE), under the assumption that their DE frequencies are comparable. The multiple transition from wakefulness to REM sleep (sleep onset REM period: SOREMP) during the five trials of the Multiple Sleep Latency Test (MSLT) appears of particular interest. In MSLT studies, NT1 patients reported a DE after about 80% of SOREMP naps (as often as after nighttime REM sleep of themselves and healthy subjects), but only after about 30% of NREM naps compared to 60% of daytime and nighttime NREM sleep of healthy subjects. To estimate accurately the “real” DE frequency, we asked participants to report DE (“dream”) after each MSLT nap and, in case of failure, to specify if they were unable to retrieve any content (“white dream”) or DE did not occur (“no-dream”). The proportions of dreams, white dreams, and no dreams and the indicators of structural organization of DEs reported after NREM naps by 17 adult NT1 patients were compared with those reported by 25 subjects with subjective complaints of excessive daytime sleepiness (sc-EDS), who take multiple daytime NREM naps. Findings were consistent with the hypothesis of a failure in recall after awakening rather than in generation during sleep: white dreams were more frequent in NT1 patients than in sc-EDS subjects (42.86 vs 17.64%), while their frequency of dreams plus white dreams were similar (67.86 and 61.78%) and comparable with that of NREM-DEs in healthy subjects. The longer and more complex NREM-DEs of NT1 patients compared with sc-EDS subjects suggest that the difficulty in DE reporting depends on their negative attitude toward recall of contents less vivid and bizarre than those they usually retrieve after daytime SOREMP and nighttime REM sleep. As this attitude may be reversed by some recall training before MSLT, collecting wider amounts of DE reports after NREM naps would cast light on both the across-stage continuity in the functioning of cognitive processes underlying DE and the difference in content and structural organization of SOREM-DEs preceded by N1 or also N2 sleep.

Hyperbaric oxygenation increases arousal and breathing movements in fetal lambs

1994 ◽  
Vol 77 (2) ◽  
pp. 902-911 ◽  
Author(s):  
M. H. Tiktinsky-Rupp ◽  
S. U. Hasan ◽  
B. Bishop ◽  
F. C. Morin
Keyword(s):  
Eye Movement ◽  
Hyperbaric Oxygenation ◽  
Nrem Sleep ◽  
Absolute Pressure ◽  
Rapid Eye Movement ◽  
Rapid Eye Movement Sleep ◽  
Fetal Sheep ◽  
Arterial Blood ◽  
Group 2 ◽  
Group 1

Oxygenation produced by distending the lungs with 100% O2 increases the occurrence of arousal and fetal breathing movements (FBM), particularly during non-rapid-eye-movement (NREM) sleep, in fetal sheep of > or = 135 days of gestation. We studied the breathing and behavioral responses to a rise in arterial PO2 (PaO2) without lung distension in fetuses between 128 and 132 days of gestation. Twelve fetuses were chronically instrumented to record FBM, behavioral state, blood pressure, arterial blood gas tensions, and pH. Fetal PaO2 was raised by having the ewe breathe 100% O2 at 3 atmosphere absolute pressure spontaneously (group 1, n = 5, 129 +/- 1 days of gestation) or with mechanical ventilation to control fetal arterial PCO2 (group 2, n = 7, 131 +/- 1 days of gestation). Hyperbaric oxygenation raised fetal PaO2 by 20 Torr in both groups. During hyperbaric oxygenation, the occurrence of arousal increased severalfold in both groups. The occurrence of FBM increased during arousal in both groups, during rapid-eye-movement sleep in group 1, and during NREM sleep in group 2. The timing of diaphragmatic activity during arousal and the variability of diaphragmatic activity during NREM sleep were different than those in rapid-eye-movement sleep. We conclude that oxygenation without lung distension increases the occurrence of arousal and of FBM, principally during arousal and NREM sleep, in fetuses of > or = 135 days of gestation.

Lateral hypothalamus-zona incerta region as an output station for the catalepsy induced by the blockade of striatal D1 and D2 dopamine receptors

1990 ◽  
Vol 506 (2) ◽  
pp. 311-315 ◽  
Author(s):  
Krystyna Ossowska ◽  
Jadwiga Wardas ◽  
Krystyna Golembiowska ◽  
Stanislaw Wolfarth
Keyword(s):  
Dopamine Receptors ◽  
Lateral Hypothalamus ◽  
Zona Incerta ◽  
D2 Dopamine Receptors

NREM delta stimulation following MK-801 is a response of sleep systems

1996 ◽  
Vol 76 (6) ◽  
pp. 3714-3720 ◽  
Author(s):  
I. G. Campbell ◽  
I. Feinberg
Keyword(s):  
Sleep Deprivation ◽  
Eye Movement ◽  
Time Course ◽  
Sleep Onset ◽  
Nrem Sleep ◽  
Rapid Eye Movement ◽  
Mk 801 ◽  
Regulatory Systems ◽  
Sleep Centers ◽  
Electroencephalogram Eeg

1. We have previously shown that noncompetitive blockade of the N-methyl-D-aspartate (NMDA)-gated cation channel with ketamine or Dizocilpine maleate (MK-801) increases the intensity of non-rapid-eye-movement (NREM) delta during subsequent sleep. This delta increase [measured as integrated amplitude (IA) in 1- to 4-Hz electroencephalogram (EEG)] occurs in the 12-h period following intraperitoneal injection. However, the 12 h after drug injection is also the period in which these drugs induce neurotoxic changes, raising the possibility that the increased delta represents toxic EEG slowing rather than an increase in the physiological delta waves of NREM sleep. 2. We hypothesized that the time course of delta stimulation could be separated from the time course of neurotoxicity. We tested this hypothesis by injecting 0.3 mg/kg MK-801 at the start of the dark period (DP) and depriving rats of sleep until the onset of the light period (LP) 12 h later. 3. There were two control groups: one received MK-801 at the start of the DP with no further manipulation, and the second received a saline injection at DP onset followed by 12 h of sleep deprivation. The dependent variable was the amount of delta IA in the LP, whose onset was 12 h after MK-801 injection. Total IA in the LP was significantly greater in rats that received MK-801 followed by sleep deprivation than in rats that received sleep deprivation alone or MK-801 alone. 4. This finding indicates that delta stimulation by MK-801 is maintained over 12 h of waking, indicating that the delta increase is not due to toxic EEG slowing or persisting MK-801. Instead, NMDA channel blockade by MK-801 increases the homeostatic need for delta or else directly alters sleep regulatory systems. We speculate that these effects are mediated by hypothalamic sleep centers through control of neuroendocrine pulses that produce both NREM and rapid-eye-movement sleep. 5. Imposing a period of waking between drug administration and sleep onset may prove a generally useful strategy for determining whether a drug affects the homeostatic need for sleep or acutely stimulates sleep systems. This strategy can also help distinguish between toxic and physiological increases in delta EEG.

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