scholarly journals State-dependent pontine ensemble dynamics and interactions with cortex across sleep states

2019 ◽  
Author(s):  
Tomomi Tsunematsu ◽  
Amisha A Patel ◽  
Arno Onken ◽  
Shuzo Sakata
Keyword(s):  
Rem Sleep ◽  
Hippocampal Neurons ◽  
Specific Activity ◽  
Nrem Sleep ◽  
Dependent Manner ◽  
Sleep Regulation ◽  
Population Activity ◽  
P Waves ◽  
State Dependent ◽  
Global Coordination

AbstractThe pontine nuclei play a crucial role in sleep-wake regulation. However, pontine ensemble dynamics underlying sleep regulation remain poorly understood. By monitoring population activity in multiple pontine and adjacent brainstem areas, here we show slow, state-predictive pontine ensemble dynamics and state-dependent interactions between the pons and the cortex in mice. On a timescale of seconds to minutes, pontine populations exhibit diverse firing across vigilance states, with some of these dynamics being attributed to cell type-specific activity. Pontine population activity can predict pupil dilation and vigilance states: pontine neurons exhibit longer predictable power compared with hippocampal neurons. On a timescale of sub-seconds, pontine waves (P-waves) are observed as synchronous firing of pontine neurons primarily during rapid eye movement (REM) sleep, but also during non-REM (NREM) sleep. Crucially, P-waves functionally interact with cortical activity in a state-dependent manner: during NREM sleep, hippocampal sharp wave-ripples (SWRs) precede P-waves. On the other hand, P-waves during REM sleep are phase-locked with ongoing hippocampal theta oscillations and are followed by burst firing in a subset of hippocampal neurons. Thus, the directionality of functional interactions between the hippocampus and pons changes depending on sleep states. This state-dependent global coordination between pontine and cortical regions implicates distinct functional roles of sleep.

scholarly journals State-dependent brainstem ensemble dynamics and their interactions with hippocampus across sleep states

eLife ◽  
2020 ◽  
Vol 9 ◽  
Author(s):  
Tomomi Tsunematsu ◽  
Amisha A Patel ◽  
Arno Onken ◽  
Shuzo Sakata
Keyword(s):  
Nrem Sleep ◽  
Dependent Manner ◽  
Sleep Regulation ◽  
P Waves ◽  
Ca1 Neurons ◽  
Functional Roles ◽  
Synchronous Firing ◽  
State Dependent ◽  
Hippocampal Ca1 ◽  
Global Coordination

The brainstem plays a crucial role in sleep-wake regulation. However, the ensemble dynamics underlying sleep regulation remain poorly understood. Here, we show slow, state-predictive brainstem ensemble dynamics and state-dependent interactions between the brainstem and the hippocampus in mice. On a timescale of seconds to minutes, brainstem populations can predict pupil dilation and vigilance states and exhibit longer prediction power than hippocampal CA1 neurons. On a timescale of sub-seconds, pontine waves (P-waves) are accompanied by synchronous firing of brainstem neurons during both rapid eye movement (REM) and non-REM (NREM) sleep. Crucially, P-waves functionally interact with CA1 activity in a state-dependent manner: during NREM sleep, hippocampal sharp wave-ripples (SWRs) precede P-waves. On the other hand, P-waves during REM sleep are phase-locked with ongoing theta oscillations and are followed by burst firing of CA1 neurons. This state-dependent global coordination between the brainstem and hippocampus implicates distinct functional roles of sleep.

scholarly journals Arousal-State Dependent Alterations in VTA-GABAergic Neural Activity

2019 ◽  
Author(s):  
Ada Eban-Rothschild ◽  
Jeremy C. Borniger ◽  
Gideon Rothschild ◽  
William J. Giardino ◽  
Joshua G. Morrow ◽  
...  
Keyword(s):  
Ventral Tegmental Area ◽  
Neuronal Activity ◽  
Rem Sleep ◽  
Neural Activity ◽  
Dopaminergic Neurons ◽  
Nrem Sleep ◽  
Gabaergic Neurons ◽  
Population Activity ◽  
Arousal State ◽  
State Dependent

AbstractDecades of research have implicated the ventral tegmental area (VTA) in motivation, reinforcement learning and reward processing. We and others recently demonstrated that it also serves as an important node in sleep/wake circuitry. Specifically, VTA-dopaminergic neuron activation is sufficient to drive wakefulness and necessary for the maintenance of wakefulness. However, the role of VTA gamma-aminobutyric acid (GABA)-expressing neurons in arousal regulation is not fully understood. It is still unclear whether VTA-GABAergic neurons predictably alter their firing properties across arousal states, what is the nature of interactions between VTA-GABAergic activity and cortical neural oscillations, and how activity in VTA-GABAergic neurons relates to VTA-dopaminergic neurons in the context of sleep/wake regulation. To address these questions, we simultaneously recorded population activity from VTA-GABAergic or VTA-dopaminergic neurons and EEG/EMG signals during spontaneous sleep/wake states and in the presence of salient stimuli in freely-behaving male mice. We observed that VTA-GABAergic neurons exhibit robust arousal-state-dependent alterations in population activity, with high activity and calcium transients during wakefulness and rapid-eye-movement (REM) sleep compared to non-REM (NREM) sleep. During wakefulness, population activity of VTA-GABAergic neurons, but not VTA-dopaminergic neurons, was positively correlated with EEG gamma power and negatively correlated with EEG theta power. During NREM sleep, population activity in both VTA-GABAergic and VTA-dopaminergic neurons negatively correlated with delta, theta, and sigma EEG power bands. Salient stimuli, with both positive and negative valence, activated VTA-GABAergic neurons. The strongest activation was observed for social stimuli irrespective of valence. Together, our data indicate that VTA-GABAergic neurons, like their dopaminergic counterparts, drastically alter their activity across sleep-wake states. Changes in their activity predicts cortical oscillatory patterns reflected in the EEG, which are distinct from EEG spectra associated with dopaminergic neural activity.Statement of SignificanceLittle is known about how ventral tegmental area (VTA) neural ensembles couple arousal to motivated behaviors. Using cell-type specific genetic tools, we investigated the population activity of GABAergic and dopaminergic neurons within the VTA across sleep/wake states and in the presence of salient stimuli. We demonstrate that coordinated neural activity within VTA-GABAergic neurons peaks during wakefulness and REM sleep. Furthermore, neuronal activity in VTA-GABAergic neurons is correlated with high frequency, low amplitude cortical oscillations during waking, but negatively correlated with high amplitude slower frequency oscillations during NREM sleep. Our results demonstrate that VTA-GABAergic neuronal activity is tightly linked to cortical arousal and highlight this population as a potential important node in sleep/wake regulation.

scholarly journals 0074 Inhibitory Neurons in the Dorsomedial Medulla Promote REM Sleep

SLEEP ◽  
2020 ◽  
Vol 43 (Supplement_1) ◽  
pp. A30-A30
Author(s):  
J Stucynski ◽  
A Schott ◽  
J Baik ◽  
J Hong ◽  
F Weber ◽  
...  
Keyword(s):  
Rem Sleep ◽  
Nrem Sleep ◽  
Inhibitory Neurons ◽  
Brain State ◽  
Sleep Regulation ◽  
Optogenetic Stimulation ◽  
Electrophysiological Recordings ◽  
Stimulation Of

Abstract Introduction The neural circuits controlling rapid eye movement (REM) sleep, and in particular the role of the medulla in regulating this brain state, remains an active area of study. Previous electrophysiological recordings in the dorsomedial medulla (DM) and electrical stimulation experiments suggested an important role of this area in the control of REM sleep. However the identity of the involved neurons and their precise role in REM sleep regulation are still unclear. Methods The properties of DM GAD2 neurons in mice were investigated through stereotaxic injection of CRE-dependent viruses in conjunction with implantation of electrodes for electroencephalogram (EEG) and electromyogram (EMG) recordings and optic fibers. Experiments included in vivo calcium imaging (fiber photometry) across sleep and wake states, optogenetic stimulation of cell bodies, chemogenetic excitation and suppression (DREADDs), and connectivity mapping using viral tracing and optogenetics. Results Imaging the calcium activity of DM GAD2 neurons in vivo indicates that these neurons are most active during REM sleep. Optogenetic stimulation of DM GAD2 neurons reliably triggered transitions into REM sleep from NREM sleep. Consistent with this, chemogenetic activation of DM GAD2 neurons increased the amount of REM sleep while inhibition suppressed its occurrence and enhanced NREM sleep. Anatomical tracing revealed that DM GAD2 neurons project to several areas involved in sleep / wake regulation including the wake-promoting locus coeruleus (LC) and the REM sleep-suppressing ventrolateral periaquaductal gray (vlPAG). Optogenetic activation of axonal projections from DM to LC, and DM to vlPAG was sufficient to induce REM sleep. Conclusion These experiments demonstrate that DM inhibitory neurons expressing GAD2 powerfully promote initiation of REM sleep in mice. These findings further characterize the dorsomedial medulla as a critical structure involved in REM sleep regulation and inform future investigations of the REM sleep circuitry. Support R01 HL149133

Vigilance state-dependent attenuation of hypercapnic chemoreflex and exaggerated sleep apnea in orexin knockout mice

2007 ◽  
Vol 102 (1) ◽  
pp. 241-248 ◽  
Author(s):  
Akira Nakamura ◽  
Wei Zhang ◽  
Masashi Yanagisawa ◽  
Yasuichiro Fukuda ◽  
Tomoyuki Kuwaki
Keyword(s):  
Rem Sleep ◽  
Knockout Mice ◽  
Slow Wave Sleep ◽  
Ventilatory Response ◽  
Control Of Breathing ◽  
Dependent Manner ◽  
Wild Type ◽  
Vigilance State ◽  
State Dependent ◽  
Respiratory Parameters

Exogenous administration of orexin can promote wakefulness and respiration. Here we examined whether intrinsic orexin participates in the control of breathing in a vigilance state-dependent manner. Ventilation was recorded together with electroencephalography and electromyography for 6 h during the daytime in prepro-orexin knockout mice (ORX-KO) and wild-type (WT) littermates. Respiratory parameters were separately determined during quiet wakefulness (QW), slow-wave sleep (SWS), or rapid eye movement (REM) sleep. Basal ventilation was normal in ORX-KO, irrespective of vigilance states. The hypercapnic ventilatory response during QW in ORX-KO (0.19 ± 0.01 ml·min−1·g−1·%CO2−1) was significantly smaller than that in WT mice (0.38 ± 0.04 ml·min−1·g−1·%CO2−1), whereas the responses during SWS and REM in ORX-KO were comparable to those in WT mice. Hypoxic responses during wake and sleep periods were not different between the genotypes. Spontaneous but not postsigh sleep apneas were more frequent in ORX-KO than in WT littermates during both SWS and REM sleep. Our findings suggest that orexin plays a crucial role both in CO2 sensitivity during wakefulness and in preserving ventilation stability during sleep.

scholarly journals 0156 Activation of Glutamatergic PPT Neurons and Their Projections Promotes Arousal, and Distinct Wake Behaviors

SLEEP ◽  
2020 ◽  
Vol 43 (Supplement_1) ◽  
pp. A61-A62
Author(s):  
D Kroeger ◽  
J A Thundercliffe ◽  
A Phung ◽  
C Geraci ◽  
R DeLuca ◽  
...  
Keyword(s):  
Substantia Nigra ◽  
Optical Fibers ◽  
Lateral Hypothalamus ◽  
Rem Sleep ◽  
Basal Forebrain ◽  
Viral Vector ◽  
Nrem Sleep ◽  
Blue Laser ◽  
Dependent Manner ◽  
Glutamatergic Neurons

Abstract Introduction The pedunculopontine tegmental (PPT) region in the brainstem is crucial for the regulation of sleep/wake states. We recently showed that chemogenetic activation of glutamatergic PPT neurons promotes wakefulness for several hours. Here we used optogenetic activation of these neurons to further investigate the mechanisms and pathways through which PPT glutamatergic neurons produce wakefulness. Methods Using vGlut2-cre mice, we transfected neurons in the PPT region with a viral vector coding for cre-dependent ChR2 tagged with fluorescent mCherry and implanted bilateral optical fibers above the PPT nuclei as well as EEG/EMG leads. Two weeks later, we administered blue laser light to activate ChR2-expressing neurons and recorded sleep/wake states. Results Activation of ChR2-expressing glutamatergic neurons during NREM sleep rapidly elicited wakefulness in a stimulation-frequency dependent manner, with higher frequencies producing wake more quickly and with longer duration. Random, automated stimulation for 10 s at 5 Hz over 24 h revealed that activation of glutamatergic PPT neurons produces rapid arousals form NREM sleep. Importantly, stimulation did not wake mice from REM sleep, suggesting that glutamatergic PPT signaling does not interfere with REM sleep. To map the target areas through which PPT glut neurons produce wakefulness, we used a viral tracer to visualize PPT glutamatergic projections, and then optogenetically stimulated terminals in 1) basal forebrain, 2) lateral hypothalamus, 3) thalamus, and 4) substantia nigra. We found that stimulating terminals in all of these regions woke mice from NREM sleep, and stimulating terminals in the basal forebrain and lateral hypothalamus produced a number of active wake behaviors such as locomotion. In contrast, stimulation of PPT glut soma and terminals in the thalamus and substantia nigra results mainly in quiet wakefulness. Conclusion Glutamatergic PPT neurons potently promote arousal from NREM sleep but not REM sleep, and the resulting wake behavior is modulated by different projection targets. Support NIH grant P01 - HL095491

The Regulation of Sleep

2021 ◽  
Author(s):  
Craig Heller
Keyword(s):  
Eye Movement ◽  
Rem Sleep ◽  
Nrem Sleep ◽  
Control Mechanisms ◽  
Rapid Eye Movement ◽  
Sleep Regulation ◽  
Short Article ◽  
Feedback Information ◽  
State Changes ◽  
And Control

The words “regulation” and “control” have different meanings. A rich literature exists on the control mechanisms of sleep—the genomic, molecular, cellular, and circuit processes responsible for arousal state changes and characteristics. The regulation of sleep refers to functions and homeostatic maintenance of those functions. Much less is known about sleep regulation than sleep control, largely because functions of sleep are still unknown. Regulation requires information about the regulated variable that can be used as feedback information to achieve optimal levels. The circadian timing of sleep is regulated, and the feedback information is entraining stimuli such as the light–dark cycle. Sleep itself is homeostatically regulated, as evidenced by sleep deprivation experiments. Eletroenceophalography (EEG) slow-wave activity (SWA) is regulated, and it appears that adenosine is the major source of feedback information, and that fact indicates an energetic function for sleep. The last aspect of sleep regulation discussed in this short article is the non-rapid eye movement (NREM) and rapid eye movement (REM) sleep cycling. Evidence is discussed that supports the argument that NREM sleep is in a homeostatic relationship with wake, and REM sleep is in a homeostatic relationship with NREM sleep.

Cholinergic reticular mechanisms influence state-dependent ventilatory response to hypercapnia

1991 ◽  
Vol 261 (3) ◽  
pp. R738-R746 ◽  
Author(s):  
R. Lydic ◽  
H. A. Baghdoyan ◽  
R. Wertz ◽  
D. P. White
Keyword(s):  
Eye Movement ◽  
Rem Sleep ◽  
Ventilatory Response ◽  
Minute Ventilation ◽  
Respiratory Control ◽  
Nrem Sleep ◽  
Neural Mechanisms ◽  
Rapid Eye Movement ◽  
State Dependent ◽  
First Time

Breathing is impaired by the loss of wakefulness that accompanies sleep, certain comatose states, and anesthesia. Although state-dependent decrements in breathing and the ability to respond to hypercapnic stimuli are characteristic of most mammals, the neural mechanisms that cause state-dependent changes in respiratory control remain poorly understood. The present study examined the hypothesis that cholinergic mechanisms in the medial pontine reticular formation (mPRF) can cause state-dependent changes in breathing and in the hypercapnic ventilatory response (HCVR). Six cats were anesthetized with halothane and chronically instrumented for subsequent studies of breathing during wakefulness, non-rapid-eye-movement (NREM) sleep, rapid-eye-movement (REM) sleep, and during the REM sleep-like state caused by mPRF microinjections of carbachol or bethanechol. Minute ventilation was significantly decreased during the carbachol-induced REM sleep-like state (DCarb) compared with wakefulness. The HCVR in NREM, REM, DCarb, and after bethanechol was less than the waking HCVR. These results show for the first time that cholinoceptive regions in the mPRF can cause state-dependent reductions in normocapnic minute ventilation and in the ventilatory response to hypercapnia.

scholarly journals Estradiol modulates recovery of REM sleep in a time-of-day-dependent manner

2013 ◽  
Vol 305 (3) ◽  
pp. R271-R280 ◽  
Author(s):  
Michael D. Schwartz ◽  
Jessica A. Mong
Keyword(s):  
Rem Sleep ◽  
Nrem Sleep ◽  
Estradiol Benzoate ◽  
Time Of Day ◽  
Female Rats ◽  
Dark Phase ◽  
Dependent Manner ◽  
Light Phase ◽  
Sleep Complaints ◽  
Hormonal Milieu

Ovarian hormones are thought to modulate sleep and fluctuations in the hormonal milieu are coincident with sleep complaints in women. In female rats, estradiol increases waking and suppresses sleep. In this study, we asked whether this effect is mediated via circadian or homeostatic regulatory mechanisms. Ovariectomized female rats received daily injections of estradiol benzoate (EB) or sesame oil that mimicked the rapid increase and subsequent decline of circulating estradiol at proestrus. In one experiment, animals were sleep deprived for 6 h starting at lights-on, so that recovery began in the mid-light phase; in the second experiment, animals were sleep deprived starting in the mid-light phase, so that recovery began at lights-off. EB suppressed baseline rapid eye movement (REM) and non-REM (NREM) sleep and increased waking in the dark phase. In both experiments, EB enhanced REM recovery in the light phase while suppressing it in the dark compared with oil; this effect was most pronounced in the first 6 h of recovery. By contrast, NREM recovery was largely unaffected by EB. In summary, EB enhanced waking and suppressed sleep, particularly REM sleep, in the dark under baseline and recovery conditions. These strong temporally dependent effects suggest that EB consolidates circadian sleep-wake rhythms in female rats.

scholarly journals Optogenetic activation of cholinergic neurons in the PPT or LDT induces REM sleep

2014 ◽  
Vol 112 (2) ◽  
pp. 584-589 ◽  
Author(s):  
Christa J. Van Dort ◽  
Daniel P. Zachs ◽  
Jonathan D. Kenny ◽  
Shu Zheng ◽  
Rebecca R. Goldblum ◽  
...  
Keyword(s):  
Rem Sleep ◽  
Cholinergic Neurons ◽  
Nrem Sleep ◽  
Sleep Regulation ◽  
Natural Sleep ◽  
Sleep Episode ◽  
Episode Duration ◽  
Laterodorsal Tegmentum ◽  
Mesopontine Tegmentum

Rapid eye movement (REM) sleep is an important component of the natural sleep/wake cycle, yet the mechanisms that regulate REM sleep remain incompletely understood. Cholinergic neurons in the mesopontine tegmentum have been implicated in REM sleep regulation, but lesions of this area have had varying effects on REM sleep. Therefore, this study aimed to clarify the role of cholinergic neurons in the pedunculopontine tegmentum (PPT) and laterodorsal tegmentum (LDT) in REM sleep generation. Selective optogenetic activation of cholinergic neurons in the PPT or LDT during non-REM (NREM) sleep increased the number of REM sleep episodes and did not change REM sleep episode duration. Activation of cholinergic neurons in the PPT or LDT during NREM sleep was sufficient to induce REM sleep.

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.

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