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 Selectively driving cholinergic fibers optically in the thalamic reticular nucleus promotes sleep

eLife ◽  
2016 ◽  
Vol 5 ◽  
Author(s):  
Kun-Ming Ni ◽  
Xiao-Jun Hou ◽  
Ci-Hang Yang ◽  
Ping Dong ◽  
Yue Li ◽  
...  
Keyword(s):  
Eye Movement ◽  
Nicotinic Acetylcholine Receptors ◽  
Rem Sleep ◽  
Sleep Onset ◽  
Cholinergic Neurons ◽  
Nrem Sleep ◽  
Gabaergic Neurons ◽  
Thalamic Reticular Nucleus ◽  
Reticular Nucleus ◽  
Rapid Eye Movement

Cholinergic projections from the basal forebrain and brainstem are thought to play important roles in rapid eye movement (REM) sleep and arousal. Using transgenic mice in which channelrhdopsin-2 is selectively expressed in cholinergic neurons, we show that optical stimulation of cholinergic inputs to the thalamic reticular nucleus (TRN) activates local GABAergic neurons to promote sleep and protect non-rapid eye movement (NREM) sleep. It does not affect REM sleep. Instead, direct activation of cholinergic input to the TRN shortens the time to sleep onset and generates spindle oscillations that correlate with NREM sleep. It does so by evoking excitatory postsynaptic currents via α7-containing nicotinic acetylcholine receptors and inducing bursts of action potentials in local GABAergic neurons. These findings stand in sharp contrast to previous reports of cholinergic activity driving arousal. Our results provide new insight into the mechanisms controlling sleep.

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

2020 ◽  
Author(s):  
Alejandra Mondino ◽  
Viviane Hambrecht-Wiedbusch ◽  
Duan Li ◽  
A. Kane York ◽  
Dinesh Pal ◽  
...  
Keyword(s):  
Eye Movement ◽  
Rem Sleep ◽  
Preoptic Area ◽  
Sleep Onset ◽  
Nrem Sleep ◽  
State Transitions ◽  
Rapid Eye Movement ◽  
Cortical Dynamics ◽  
Glutamatergic Neurons ◽  
Conditional Expression

ABSTRACTClinical and experimental data from the last nine decades indicate that the preoptic area of the hypothalamus is a critical node in a brain network that controls sleep onset and homeostasis. By contrast, we recently reported that a group of glutamatergic neurons in the lateral and medial preoptic area increases wakefulness, challenging the long-standing notion in sleep neurobiology that the preoptic area is exclusively somnogenic. However, the precise role of these subcortical neurons in the control of behavioral state transitions and cortical dynamics remains unknown. Therefore, in this study we used conditional expression of excitatory hM3Dq receptors in these preoptic glutamatergic (Vglut2+) neurons and show that their activation initiates wakefulness, decreases non-rapid eye movement (NREM) sleep, and causes a persistent suppression of rapid eye movement (REM) sleep. Activation of preoptic glutamatergic neurons also causes a high degree of NREM sleep fragmentation, promotes state instability with frequent arousals from sleep, and shifts cortical dynamics (including oscillations, connectivity, and complexity) to a more wake-like state. We conclude that a subset of preoptic glutamatergic neurons may initiate -but not maintain- arousals from sleep, and their inactivation may be required for NREM stability and REM sleep generation. Further, these data provide novel empirical evidence supporting the conclusion that the preoptic area causally contributes to the regulation of both sleep and wakefulness.

scholarly journals GABA neurons in the ventral tegmental area regulate non-rapid eye movement sleep in mice

2019 ◽  
Author(s):  
Srikanta Chowdhury ◽  
Takanori Matsubara ◽  
Toh Miyazaki ◽  
Daisuke Ono ◽  
Manabu Abe ◽  
...  
Keyword(s):  
Ventral Tegmental Area ◽  
Eye Movement ◽  
Rem Sleep ◽  
Nrem Sleep ◽  
Neural Circuitry ◽  
Acid Decarboxylase ◽  
Rapid Eye Movement ◽  
Population Activity ◽  
Ventral Tegmental

AbstractThe daily sleep/wakefulness cycle is regulated by coordinated interactions between sleep- and wakefulness-regulating neural circuitry. However, the detailed neural circuitry mediating sleep is far from understood. Here, we found that glutamic acid decarboxylase 67 (Gad67)-positive GABAergic neurons in the ventral tegmental area (VTAGad67+) are a key regulator of non-rapid eye movement (NREM) sleep in mice. VTAGad67+ neurons project to multiple brain areas implicated in sleep/wakefulness regulation such as the lateral hypothalamus (LH) and dorsal raphe nucleus. Chemogenetic activation of VTAGad67+ neurons promoted NREM sleep with higher delta power whereas optogenetic inhibition of these neurons induced prompt arousal from NREM sleep under highly somnolescent conditions, but not during REM sleep. In vivo fiber photometry recordings revealed that VTAGad67+ neurons showed the highest population activity in NREM sleep and the lowest activity in REM sleep. Acute brain slice electrophysiology combined with optogenetics revealed that VTAGad67+ neurons directly innervate and inhibit wake-promoting orexin/hypocretin neurons in the LH by releasing GABA. Taken together, we reveal that VTAGad67+ neurons play a crucial role in the regulation of NREM sleep.

scholarly journals Neurophysiological control of sleep with special emphasis on melatonin

2020 ◽  
Vol 18 (4) ◽  
pp. 355-376
Author(s):  
Iv. Penchev Georgiev
Keyword(s):  
Sleep Disorders ◽  
Eye Movement ◽  
Rem Sleep ◽  
Sleep Onset ◽  
Vascular Diseases ◽  
Nrem Sleep ◽  
Brain Structures ◽  
Rapid Eye Movement ◽  
Human Beings ◽  
Melatonin Receptor Agonists

Sleep and wakefulness are two main types of human and animal behavior. On the average human beings spend about one-third of their lives asleep. The sleep-wake cycle is the most important circadian rhythms which alternates in a periodic manner lasting for about 24 hours. Sleep is determined as the natural periodic suspension of consciousness characterized by relative immobility and reduced responsiveness to external stimuli. The researchers have found and identified many special brain structures and systems controlling waking, rapid eye movement (REM) sleep and non-rapid eye (NREM) sleep and the transitions among these states. Currently, there is an enhanced interest of researchers toward sleep and its neurophysiological mechanisms of regulation because the number of people suffering from various sleep disturbance such as insomnia, delayed sleep onset, duration and propensity of sleep, worldwide dramatically increases. In addition to the next day drowsiness, nervousness, tiredness and decreased workability, it has been suggested that sleep is important also for the maintaining of mood, memory and cognitive function of the brain and is essential for the normal functioning of the endocrine and immune systems. More recently, new studies show a sustained link between sleep disorders and different serious health problems, including obesity, insulin resistance, type 2 diabetes mellitus, cardio-vascular diseases and depression. Therefore, the purpose of this review is to summarize and analyze the available data about the neurological control of wakefulness, non-rapid-eye-movement (NREM) sleep and rapid- eye-movement (REM) sleep creating a substantial basis for better understanding different sleep disorders. Special attention is paid on the pharmacological aspects and use of some new classes of sleep promoting agents – melatonin, melatonin receptor agonists and orexin receptor antagonists.

scholarly journals Structural organization of dream experience during daytime sleep-onset rapid eye movement period sleep of patients with narcolepsy type 1

SLEEP ◽  
2020 ◽  
Vol 43 (8) ◽  
Author(s):  
Carlo Cipolli ◽  
Fabio Pizza ◽  
Claudia Bellucci ◽  
Michela Mazzetti ◽  
Giovanni Tuozzi ◽  
...  
Keyword(s):  
Eye Movement ◽  
Rem Sleep ◽  
Structural Organization ◽  
Sleep Onset ◽  
Nrem Sleep ◽  
Rapid Eye Movement ◽  
Story Grammar ◽  
Late Night ◽  
Grammar Analysis

Abstract Study Objective To assess the frequency of dream experience (DE) developed during naps at Multiple Sleep Latency Test (MSLT) by patients with narcolepsy type 1 (NT1) and establish, using story-grammar analysis, the structural organization of DEs developed during naps with sleep onset rapid eye movement (REM) period (SOREMP) sleep compared with their DEs during early- and late-night REM sleep. Methods Thirty drug-free cognitively intact adult NT1 patients were asked to report DE developed during each MSLT nap. Ten NT1 patients also spent voluntarily a supplementary night being awakened during the first-cycle and third-cycle REM sleep. Patients provided dream reports, white dreams, and no dreams, whose frequencies were matched in naps with SOREMP versus non-REM (NREM) sleep. All dream reports were then analyzed using story-grammar rules. Results DE was recalled in detail (dream report) by NT1 patients after 75% of naps with SOREMP sleep and after 25% of naps with NREM sleep. Dream reports were provided by 8 out of 10 NT1 patients after both awakenings from nighttime REM sleep. Story-grammar analysis of dream reports showed that SOREMP-DEs are organized as hierarchically ordered sequences of events (so-called dream-stories), which are longer and more complex in the first and fourth SOREMP naps and are comparable with nighttime REM-DEs. Conclusions The similar structural organization of SOREMP-DEs with nighttime REM-DEs indicates that their underlying cognitive processes are highly, albeit not uniformly, effective during daytime SOREMP sleep. Given the peculiar neurophysiology of SOREMP sleep, investigating SOREMP-DEs may cast further light on the relationships between the neurophysiological and psychological processes involved in REM-dreaming.

Sleep Disorders

2015 ◽  
Author(s):  
Sudhansu Chokroverty
Keyword(s):  
Sleep Apnea ◽  
Sleep Disorders ◽  
Eye Movement ◽  
Rem Sleep ◽  
Sleep Apnea Syndrome ◽  
Nrem Sleep ◽  
Rapid Eye Movement ◽  
Circadian Rhythm Sleep Disorders ◽  
Apnea Syndrome ◽  
Sleep Mechanism

Recent research has generated an enormous fund of knowledge about the neurobiology of sleep and wakefulness. Sleeping and waking brain circuits can now be studied by sophisticated neuroimaging techniques that map different areas of the brain during different sleep states and stages. Although the exact biologic functions of sleep are not known, sleep is essential, and sleep deprivation leads to impaired attention and decreased performance. Sleep is also believed to have restorative, conservative, adaptive, thermoregulatory, and consolidative functions. This review discusses the physiology of sleep, including its two independent states, rapid eye movement (REM) and non–rapid eye movement (NREM) sleep, as well as functional neuroanatomy, physiologic changes during sleep, and circadian rhythms. The classification and diagnosis of sleep disorders are discussed generally. The diagnosis and treatment of the following disorders are described: obstructive sleep apnea syndrome, narcolepsy-cataplexy sydrome, idiopathic hypersomnia, restless legs syndrome (RLS) and periodic limb movements in sleep, circadian rhythm sleep disorders, insomnias, nocturnal frontal lobe epilepsy, and parasomnias. Sleep-related movement disorders and the relationship between sleep and psychiatric disorders are also discussed. Tables describe behavioral and physiologic characteristics of states of awareness, the international classification of sleep disorders, common sleep complaints, comorbid insomnia disorders, causes of excessive daytime somnolence, laboratory tests to assess sleep disorders, essential diagnostic criteria for RLS and Willis-Ekbom disease, and drug therapy for insomnia. Figures include polysomnographic recording showing wakefulness in an adult; stage 1, 2, and 3 NREM sleep in an adult; REM sleep in an adult; a patient with sleep apnea syndrome; a patient with Cheyne-Stokes breathing; a patient with RLS; and a patient with dream-enacting behavior; schematic sagittal section of the brainstem of the cat; schematic diagram of the McCarley-Hobson model of REM sleep mechanism; the Lu-Saper “flip-flop” model; the Luppi model to explain REM sleep mechanism; and a wrist actigraph from a man with bipolar disorder. This review contains 14 highly rendered figures, 8 tables, 115 references, and 5 MCQs.

Sleep Disorders

2015 ◽  
Author(s):  
Sudhansu Chokroverty
Keyword(s):  
Sleep Apnea ◽  
Sleep Disorders ◽  
Eye Movement ◽  
Rem Sleep ◽  
Sleep Apnea Syndrome ◽  
Nrem Sleep ◽  
Rapid Eye Movement ◽  
Circadian Rhythm Sleep Disorders ◽  
Apnea Syndrome ◽  
Sleep Mechanism

Recent research has generated an enormous fund of knowledge about the neurobiology of sleep and wakefulness. Sleeping and waking brain circuits can now be studied by sophisticated neuroimaging techniques that map different areas of the brain during different sleep states and stages. Although the exact biologic functions of sleep are not known, sleep is essential, and sleep deprivation leads to impaired attention and decreased performance. Sleep is also believed to have restorative, conservative, adaptive, thermoregulatory, and consolidative functions. This review discusses the physiology of sleep, including its two independent states, rapid eye movement (REM) and non–rapid eye movement (NREM) sleep, as well as functional neuroanatomy, physiologic changes during sleep, and circadian rhythms. The classification and diagnosis of sleep disorders are discussed generally. The diagnosis and treatment of the following disorders are described: obstructive sleep apnea syndrome, narcolepsy-cataplexy sydrome, idiopathic hypersomnia, restless legs syndrome (RLS) and periodic limb movements in sleep, circadian rhythm sleep disorders, insomnias, nocturnal frontal lobe epilepsy, and parasomnias. Sleep-related movement disorders and the relationship between sleep and psychiatric disorders are also discussed. Tables describe behavioral and physiologic characteristics of states of awareness, the international classification of sleep disorders, common sleep complaints, comorbid insomnia disorders, causes of excessive daytime somnolence, laboratory tests to assess sleep disorders, essential diagnostic criteria for RLS and Willis-Ekbom disease, and drug therapy for insomnia. Figures include polysomnographic recording showing wakefulness in an adult; stage 1, 2, and 3 NREM sleep in an adult; REM sleep in an adult; a patient with sleep apnea syndrome; a patient with Cheyne-Stokes breathing; a patient with RLS; and a patient with dream-enacting behavior; schematic sagittal section of the brainstem of the cat; schematic diagram of the McCarley-Hobson model of REM sleep mechanism; the Lu-Saper “flip-flop” model; the Luppi model to explain REM sleep mechanism; and a wrist actigraph from a man with bipolar disorder. This review contains 14 highly rendered figures, 8 tables, 115 references, and 5 MCQs.

Arousal Characteristics in Patients with Parkinson’s Disease and Isolated Rapid Eye Movement Sleep Behavior Disorder

SLEEP ◽  
2021 ◽  
Author(s):  
Andreas Brink-Kjær ◽  
Matteo Cesari ◽  
Friederike Sixel-Döring ◽  
Brit Mollenhauer ◽  
Claudia Trenkwalder ◽  
...  
Keyword(s):  
Parkinson’S Disease ◽  
Eye Movement ◽  
Rem Sleep ◽  
Regression Models ◽  
Muscle Tone ◽  
Behavior Disorder ◽  
Nrem Sleep ◽  
Rapid Eye Movement ◽  
Sleep Behavior

Abstract Study objectives Patients diagnosed with isolated rapid eye movement (REM) sleep behavior disorder (iRBD) and Parkinson’s disease (PD) have altered sleep stability reflecting neurodegeneration in brainstem structures. We hypothesize that neurodegeneration alters the expression of cortical arousals in sleep. Methods We analyzed polysomnography data recorded from 88 healthy controls (HC), 22 iRBD patients, 82 de novo PD patients without RBD and 32 with RBD (PD+RBD). These patients were also investigated at a 2-year follow-up. Arousals were analyzed using a previously validated automatic system, which used a central EEG lead, electrooculography, and chin electromyography. Multiple linear regression models were fitted to compare group differences at baseline and change to follow-up for arousal index (ArI), shifts in electroencephalographic signals associated with arousals, and arousal chin muscle tone. The regression models were adjusted for known covariates affecting the nature of arousal. Results In comparison to HC, patients with iRBD and PD+RBD showed increased ArI during REM sleep and their arousals showed a significantly lower shift in α-band power at arousals and a higher muscle tone during arousals. In comparison to HC, the PD patients were characterized by a decreased ArI in NREM sleep at baseline. ArI during NREM sleep decreased further at the 2-year follow-up, although not significantly Conclusions Patients with PD and iRBD present with abnormal arousal characteristics as scored by an automated method. These abnormalities are likely to be caused by neurodegeneration of the reticular activation system due to alpha-synuclein aggregation.

scholarly journals Nonrapid eye movement sleep electroencephalographic oscillations in idiopathic rapid eye movement sleep behavior disorder: a study of sleep spindles and slow oscillations

SLEEP ◽  
2020 ◽  
Author(s):  
Jun-Sang Sunwoo ◽  
Kwang Su Cha ◽  
Jung-Ick Byun ◽  
Jin-Sun Jun ◽  
Tae-Joon Kim ◽  
...  
Keyword(s):  
Eye Movement ◽  
Rem Sleep ◽  
Rem Sleep Behavior Disorder ◽  
Behavior Disorder ◽  
Nrem Sleep ◽  
Sleep Spindles ◽  
Rapid Eye Movement ◽  
Sleep Behavior ◽  
Slow Oscillations ◽  
Lower Amplitude

Abstract Study Objectives We investigated electroencephalographic (EEG) slow oscillations (SOs), sleep spindles (SSs), and their temporal coordination during nonrapid eye movement (NREM) sleep in patients with idiopathic rapid eye movement (REM) sleep behavior disorder (iRBD). Methods We analyzed 16 patients with video-polysomnography-confirmed iRBD (age, 65.4 ± 6.6 years; male, 87.5%) and 10 controls (age, 62.3 ± 7.5 years; male, 70%). SSs and SOs were automatically detected during stage N2 and N3. We analyzed their characteristics, including density, frequency, duration, and amplitude. We additionally identified SO-locked spindles and examined their phase distribution and phase locking with the corresponding SO. For inter-group comparisons, we used the independent samples t-test or Wilcoxon rank-sum test, as appropriate. Results The SOs of iRBD patients had significantly lower amplitude, longer duration (p = 0.005 for both), and shallower slope (p < 0.001) than those of controls. The SS power of iRBD patients was significantly lower than that of controls (p = 0.002), although spindle density did not differ significantly. Furthermore, SO-locked spindles of iRBD patients prematurely occurred during the down-to-up-state transition of SOs, whereas those of controls occurred at the up-state peak of SOs (p = 0.009). The phase of SO-locked spindles showed a positive correlation with delayed recall subscores (p = 0.005) but not with tonic or phasic electromyography activity during REM sleep. Conclusions In this study, we found abnormal EEG oscillations during NREM sleep in patients with iRBD. The impaired temporal coupling between SOs and SSs may reflect early neurodegenerative changes in iRBD.

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