Loss of putative GABAergic neurons in the ventrolateral medulla in multiple system atrophy

SLEEP ◽  
2021 ◽  
Author(s):  
Ann M Schmeichel ◽  
Elizabeth A Coon ◽  
Joseph E Parisi ◽  
Wolfgang Singer ◽  
Phillip A Low ◽  
...  
Keyword(s):  
Multiple System Atrophy ◽  
Eye Movement ◽  
Rem Sleep ◽  
Respiratory Control ◽  
Gabaergic Neurons ◽  
Ventrolateral Medulla ◽  
Rapid Eye Movement ◽  
Control Subjects ◽  
Neuropathological Diagnosis

Abstract Study Objectives Multiple system atrophy (MSA) is associated with disturbances in cardiovascular, sleep and respiratory control. The lateral paragigantocellular nucleus (LPGi) in the ventrolateral medulla (VLM) contains GABAergic neurons that participate in control of rapid eye movement (REM) sleep and cardiovagal responses. We sought to determine whether there was loss of putative GABAergic neurons in the LPGi and adjacent regions in MSA. Methods Sections of the medulla were processed for GAD65/67 immunoreactivity in eight subjects with clinical and neuropathological diagnosis of MSA and in six control subjects. These putative GABAergic LPGi neurons were mapped based on their relationship to adjacent monoaminergic VLM groups. Results There were markedly decreased numbers of GAD-immunoreactive neurons in the LPGi and adjacent VLM regions in MSA. Conclusions There is loss of GABAergic neurons in the VLM, including the LPGi in patients with MSA. Whereas these findings provide a possible mechanistic substrate, given the few cases included, further studies are necessary to determine whether they contribute to REM sleep-related cardiovagal and possibly respiratory dysregulation in MSA.

scholarly journals Regulation of REM Sleep by Inhibitory Neurons in the Dorsomedial Medulla

2020 ◽  
Author(s):  
Joseph A. Stucynski ◽  
Amanda L. Schott ◽  
Justin Baik ◽  
Shinjae Chung ◽  
Franz Weber
Keyword(s):  
Eye Movement ◽  
Rem Sleep ◽  
Gabaergic Neurons ◽  
Inhibitory Neurons ◽  
Sleep Stages ◽  
Rapid Eye Movement ◽  
Rapid Eye Movement Sleep ◽  
Brain Rhythms ◽  
Slow Activity ◽  
Raphé Nuclei

ABSTRACTThe two major stages of mammalian sleep – rapid eye movement sleep (REMs) and non-REM sleep (NREMs) – are characterized by distinct brain rhythms ranging from millisecond to minute-long (infraslow) oscillations. The mechanisms controlling transitions between sleep stages and how they are synchronized with infraslow rhythms remain poorly understood. Using opto- and chemogenetic manipulation, we show that GABAergic neurons in the dorsomedial medulla (dmM) promote the initiation and maintenance of REMs, in part through their projections to the dorsal and median raphe nuclei. Fiber photometry revealed that dmM GABAergic neurons are strongly activated during REMs. During NREMs, their activity fluctuated in close synchrony with infraslow oscillations in the spindle band of the electroencephalogram, and the phase of this rhythm modulated the latency of optogenetically induced REMs episodes. Thus, dmM inhibitory neurons powerfully promote REMs, and their slow activity fluctuations may coordinate transitions from NREMs to REMs with infraslow brain rhythms.

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.

Congenital Central Hypoventilation and Sleep State

PEDIATRICS ◽  
1980 ◽  
Vol 66 (3) ◽  
pp. 425-428
Author(s):  
Peter J. Fleming ◽  
Darlene Cade ◽  
M. Heather Bryan ◽  
A. Charles Bryan
Keyword(s):  
Metabolic Control ◽  
Eye Movement ◽  
Rem Sleep ◽  
Ventilatory Response ◽  
Respiratory Control ◽  
Rapid Eye Movement ◽  
Sleep State ◽  
Quiet Sleep ◽  
Awake State ◽  
Central Hypoventilation

Congenital central hypoventilation (Ondine's curse) is described in an infant with persistant symptoms throughout the first nine months of life. Respiratory control was most severely affected in quiet sleep, although abnormalities were present in rapid eye movement (REM) sleep and while awake. Failure of metabolic control in quiet sleep led to profound hypoventilation. Behavioral or "behavioral-like" inputs in the awake state and REM sleep increased ventilation, but not to expected normal levels. The ventilatory response to inhaled 4% CO2 was markedly depressed in all states.

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 Control of Sleep and Wakefulness

2012 ◽  
Vol 92 (3) ◽  
pp. 1087-1187 ◽  
Author(s):  
Ritchie E. Brown ◽  
Radhika Basheer ◽  
James T. McKenna ◽  
Robert E. Strecker ◽  
Robert W. McCarley
Keyword(s):  
Brain Stem ◽  
Eye Movement ◽  
Rem Sleep ◽  
Emotional Reactivity ◽  
Low Voltage ◽  
Nrem Sleep ◽  
Gabaergic Neurons ◽  
Cortical Activation ◽  
Rapid Eye Movement ◽  
The Brain

This review summarizes the brain mechanisms controlling sleep and wakefulness. Wakefulness promoting systems cause low-voltage, fast activity in the electroencephalogram (EEG). Multiple interacting neurotransmitter systems in the brain stem, hypothalamus, and basal forebrain converge onto common effector systems in the thalamus and cortex. Sleep results from the inhibition of wake-promoting systems by homeostatic sleep factors such as adenosine and nitric oxide and GABAergic neurons in the preoptic area of the hypothalamus, resulting in large-amplitude, slow EEG oscillations. Local, activity-dependent factors modulate the amplitude and frequency of cortical slow oscillations. Non-rapid-eye-movement (NREM) sleep results in conservation of brain energy and facilitates memory consolidation through the modulation of synaptic weights. Rapid-eye-movement (REM) sleep results from the interaction of brain stem cholinergic, aminergic, and GABAergic neurons which control the activity of glutamatergic reticular formation neurons leading to REM sleep phenomena such as muscle atonia, REMs, dreaming, and cortical activation. Strong activation of limbic regions during REM sleep suggests a role in regulation of emotion. Genetic studies suggest that brain mechanisms controlling waking and NREM sleep are strongly conserved throughout evolution, underscoring their enormous importance for brain function. Sleep disruption interferes with the normal restorative functions of NREM and REM sleep, resulting in disruptions of breathing and cardiovascular function, changes in emotional reactivity, and cognitive impairments in attention, memory, and decision making.

scholarly journals The Relationship Between Daily Rapid-Eye Movement Sleep and Cognitive Functioning in Older Adults

2020 ◽  
Vol 4 (Supplement_1) ◽  
pp. 159-159
Author(s):  
Tiana Broen ◽  
Tomiko Yoneda ◽  
Jonathan Rush ◽  
Jamie Knight ◽  
Nathan Lewis ◽  
...  
Keyword(s):  
Older Adults ◽  
Working Memory ◽  
Cognitive Functioning ◽  
Eye Movement ◽  
Rem Sleep ◽  
Cognitive Tests ◽  
Rapid Eye Movement ◽  
Targeted Interventions ◽  
The Impact ◽  
The Relationship

Abstract Previous cross-sectional research suggests that age-related decreases in Rapid-Eye Movement (REM) sleep may contribute to poorer cognitive functioning (CF); however, few studies have examined the relationship at the intraindividual level by measuring habitual sleep over multiple days. Applying a 14-day daily diary design, the current study examines the dynamic relationship between REM sleep and CF in 69 healthy older adults (M age=70.8 years, SD=3.37; 73.9% female; 66.6% completed at least an undergraduate degree). A Fitbit device provided actigraphy indices of REM sleep (minutes and percentage of total sleep time), while CF was measured four times daily on a smartphone via ambulatory cognitive tests that captured processing speed and working memory. This research addressed the following questions: At the within-person level, are fluctuations in quantity of REM sleep associated with fluctuations in next day cognitive measures across days? Do individuals who spend more time in REM sleep on average, perform better on cognitive tests than adults who spend less time in REM sleep? A series of multilevel models were fit to examine the extent to which each index of sleep accounted for daily fluctuations in performance on next day cognitive tests. Results indicated that during nights when individuals had more REM sleep minutes than was typical, they performed better on the working memory task the next morning (estimate = -.003, SE = .002, p = .02). These results highlight the impact of REM sleep on CF, and further research may allow for targeted interventions for earlier treatment of sleep-related cognitive impairment.

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