Respiratory nuclei share synaptic connectivity with pontine reticular regions regulating REM sleep

1995 ◽  
Vol 268 (2) ◽  
pp. L251-L262 ◽  
Author(s):  
L. H. Lee ◽  
D. B. Friedman ◽  
R. Lydic
Keyword(s):  
Respiratory Depression ◽  
Rem Sleep ◽  
Minute Ventilation ◽  
Fluorescent Labeling ◽  
Respiratory Neurons ◽  
Synaptic Connectivity ◽  
Fluorescent Tracers ◽  
State Dependent ◽  
Dorsal Respiratory Group ◽  
Diamidino Yellow

Injection of cholinomimetics into the medial pontine reticular formation (mPRF) of intact, unanesthetized cat causes a rapid eye movement (REM) sleep-like state and respiratory depression. The mPRF contains no concentrations of respiratory neurons, and this study examined the hypothesis that respiratory depression evoked from the mPRF is synaptically mediated. The mPRF of conscious cats was injected with bethanechol to define an mPRF zone causing state-dependent respiratory depression. Bethanechol caused a 361% increase in the REM sleep-like state and a 37% decrease in minute ventilation. Additional cats were injected with the retrograde fluorescent tracers True Blue and either Fluoro-Gold or Diamidino Yellow aimed for the cholinoceptive mPRF or for the pontine respiratory group (PRG). After mPRF dye injection, 1) labeling was observed in the PRG, dorsal respiratory group (DRG), and ventral respiratory group (VRG); and 2) double-labeled cells were observed in the VRG and PRG. Dye injections into the PRG produced contralateral and ipsilateral fluorescent labeling of the mPRF, DRG, and VRG. Thus cholinoceptive regions of the mPRF involved in REM sleep generation have reciprocal monosynaptic connections with the PRG and receive monosynaptic projections from the DRG and VRG.

Cholinergic Pontine Mechanisms Causing State-Dependent Respiratory Depression

Physiology ◽  
1992 ◽  
Vol 7 (5) ◽  
pp. 220-224
Author(s):  
R Lydic ◽  
HA Baghdoyan
Keyword(s):  
Hypothesis Testing ◽  
Eye Movement ◽  
Respiratory Depression ◽  
Reticular Formation ◽  
Rem Sleep ◽  
Pontine Reticular Formation ◽  
Rapid Eye Movement ◽  
Cholinergic Agonists ◽  
State Dependent ◽  
Pharmacological Model

Microinjecting cholinergic agonists into the pontine reticular formation causes a rapid-eye-movement (REM) sleeplike state. The ability to cause this state pharmacologically has encouraged causal hypothesis testing. This pharmacological model has shown that cholinergic pontine mechanism known to regulate REM sleep can also cause state-dependent respiratory depression.

Pontine cholinergic reticular mechanisms cause state-dependent changes in the discharge of parabrachial neurons

1994 ◽  
Vol 266 (1) ◽  
pp. R136-R150 ◽  
Author(s):  
K. A. Gilbert ◽  
R. Lydic
Keyword(s):  
Reticular Formation ◽  
Rem Sleep ◽  
Respiratory Neurons ◽  
Pontine Reticular Formation ◽  
Limited Sample ◽  
Extracellular Recordings ◽  
Firing Rates ◽  
Nuclear Complex ◽  
State Dependent ◽  
Cholinoceptive Mechanisms

The present study examined the hypothesis that cholinoceptive reticular mechanisms in the gigantocellular tegmental field (FTG) of the medial pontine reticular formation cause state-dependent changes in the discharge of parabrachial neurons. In chronically implanted, unanesthetized cats, extracellular recordings were made from nonrespiratory and respiratory neurons in the parabrachial nuclear complex (PBNC) during the natural sleep-wake cycle and during the rapid eye movement (REM) sleeplike state caused by FTG microinjection of carbachol or neostigmine. PBNC cells that increased discharge during natural REM sleep (REM-on cells) revealed similar increased discharge during the carbachol-induced REM sleeplike state (DCarb). Cells that decreased discharge in natural REM sleep (REM-off cells) displayed decreased discharge during both DCarb and the neostigmine-induced REM sleeplike states. The limited sample of parabrachial respiratory neurons revealed significantly diminished discharge during the cholinergically induced REM sleeplike state. Thus cholinoceptive mechanisms localized to specific regions of the pontine reticular formation can cause state-dependent changes in the firing rates of respiratory and nonrespiratory neurons in the PBNC.

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.

Microdialysis of cat pons reveals enhanced acetylcholine release during state-dependent respiratory depression

1991 ◽  
Vol 261 (3) ◽  
pp. R766-R770 ◽  
Author(s):  
R. Lydic ◽  
H. A. Baghdoyan ◽  
Z. Lorinc
Keyword(s):  
Respiratory Depression ◽  
Rem Sleep ◽  
High Performance ◽  
Respiratory Control ◽  
Acetylcholinesterase Inhibitors ◽  
Brain Regions ◽  
Ach Release ◽  
Microdialysis Probe ◽  
State Dependent ◽  
Polygraphic Recording

Microinjection of cholinergic agonists and acetylcholinesterase inhibitors into the medial pontine reticular formation (mPRF) causes a state that is polygraphically similar to rapid-eye-movement (REM) sleep. Respiratory studies of intact unanesthetized cats during this cholinergically induced REM sleep-like state have shown that the same cholinoceptive pontine reticular regions that mediate REM sleep can also cause state-dependent respiratory depression. The present study investigated the hypothesis that acetylcholine (ACh) release in the mPRF is increased during the respiratory depression that accompanies the cholinergically induced REM sleep-like state. Cats were implanted for polygraphic recording of sleep and wakefulness and with guide tubes aimed for placing a microinjector in one mPRF and a microdialysis probe in the contralateral mPRF. ACh release was measured with high-performance liquid chromatography and electrochemical detection. Compared with waking levels, ACh was significantly increased and respiratory frequency was significantly decreased during the carbachol-induced REM sleep-like state. These results support the hypothesis that endogenous cholinergic neurotransmission in brain regions known to regulate REM sleep can also cause state-dependent changes in respiratory control.

Activity of respiratory neurons during hypoxia in the chemodenervated cat

1995 ◽  
Vol 78 (3) ◽  
pp. 856-861 ◽  
Author(s):  
S. J. England ◽  
J. E. Melton ◽  
M. A. Douse ◽  
J. Duffin
Keyword(s):  
Respiratory Depression ◽  
Late Onset ◽  
Respiratory Neurons ◽  
Ventral Respiratory Group ◽  
Inspiratory Neurons ◽  
Dorsal Respiratory Group ◽  
Premotor Neurons ◽  
Acute Hypoxic Hypoxia ◽  
Subsequent Loss ◽  
Initial Depression

Exposure of anesthetized paralyzed vagotomized peripherally chemodenervated cats to hypoxia results in initial depression and subsequent loss of the phrenic neurogram. To determine whether hypoxic respiratory depression results from the inhibition of respiratory premotor neurons by bulbospinal neurons of the Botzinger complex (Bot-E neurons), extracellular recordings were made of dorsal and ventral respiratory group bulbospinal inspiratory neurons and Bot-E neurons during acute hypoxic hypoxia. All neurons recorded decreased firing rate during hypoxia. Bot-E neurons became silent before the loss of phasic phrenic activity during hypoxia and commenced firing before or coincident with the return of the phrenic neurogram during reoxygenation. Inspiratory neurons ceased firing coincident with phrenic silence. Dorsal respiratory group and ventral respiratory group neurons that had a late onset of firing with respect to the phrenic neurogram during normoxia fired progressively earlier in inspiration during hypoxia, an effect that was reversed during reoxygenation. These data are consistent with inhibition and/or disfacilitation as the mechanism of hypoxic respiratory depression but suggest that Bot-E neurons are not the source of this inhibition.

Changes in upper airway muscle activation and ventilation during phasic REM sleep in normal men

1991 ◽  
Vol 71 (2) ◽  
pp. 488-497 ◽  
Author(s):  
L. Wiegand ◽  
C. W. Zwillich ◽  
D. Wiegand ◽  
D. P. White
Keyword(s):  
Eye Movements ◽  
Tidal Volume ◽  
Rem Sleep ◽  
Muscle Activation ◽  
Sleep Stage ◽  
Minute Ventilation ◽  
Upper Airway ◽  
Respiratory Neurons ◽  
Dilator Muscle ◽  
Normal Men

Several investigators have observed that irregular breathing occurs during rapid-eye-movement (REM) sleep in healthy subjects, with ventilatory suppression being prominent during active eye movements [phasic REM (PREM) sleep] as opposed to tonic REM (TREM) sleep, when ocular activity is absent and ventilation more regular. Inasmuch as considerable data suggest that rapid eye movements are a manifestation of sleep-induced neural events that may importantly influence respiratory neurons, we hypothesized that upper airway dilator muscle activation may also be suppressed during periods of active eye movements in REM sleep. We studied six normal men during single nocturnal sleep studies. Standard sleep-staging parameters, ventilation, and genioglossus and alae nasi electromyograms (EMG) were continuously recorded during the study. There were no significant differences in minute ventilation, tidal volume, or any index of genioglossus or alae nasi EMG amplitude between non-REM (NREM) and REM sleep, when REM was analyzed as a single sleep stage. Each breath during REM sleep was scored as “phasic” or “tonic,” depending on its proximity to REM deflections on the electrooculogram. Comparison of all three sleep states (NREM, PREM, and TREM) revealed that peak inspiratory genioglossus and alae nasi EMG activities were significantly decreased during PREM sleep compared with TREM sleep [genioglossus (arbitrary units): NREM 49 +/- 12 (mean +/- SE), TREM 49 +/- 5, PREM 20 +/- 5 (P less than 0.05, PREM different from TREM and NREM); alae nasi: NREM 16 +/- 4, TREM 38 +/- 7, PREM 10 +/- 4 (P less than 0.05, PREM different from TREM)]. We also observed, as have others, that ventilation, tidal volume, and mean inspiratory airflow were significantly decreased and respiratory frequency was increased during PREM sleep compared with both TREM and NREM sleep. We conclude that hypoventilation occurs in concert with reduced upper airway dilator muscle activation during PREM sleep by mechanisms that remain to be established.

Pertussis toxin-sensitive G proteins mediate carbachol-induced REM sleep and respiratory depression

1995 ◽  
Vol 269 (2) ◽  
pp. R308-R317 ◽  
Author(s):  
S. L. Shuman ◽  
M. L. Capece ◽  
H. A. Baghdoyan ◽  
R. Lydic
Keyword(s):  
Cholera Toxin ◽  
G Protein ◽  
Respiratory Depression ◽  
G Proteins ◽  
Pertussis Toxin ◽  
Rem Sleep ◽  
State Dependent ◽  
Transduction Mechanisms ◽  
Guanine Nucleotide Binding ◽  
Nucleotide Binding Proteins

Microinjecting cholinomimetics into the medial pontine reticular formation (mPRF) of conscious cats causes a rapid eye movement (REM) sleep-like state and state-dependent respiratory depression. Muscarinic receptors within the mPRF have been shown to mediate this state-dependent respiratory depression, but the specific signal transduction mechanisms remain poorly understood. This study tested the hypothesis that the cholinergically induced REM sleep-like state and state-dependent respiratory depression are mediated by guanine nucleotide binding proteins (G proteins). Cholera toxin, pertussis toxin, 5'-guanylylimidodiphosphate, and forskolin were microinjected alone and in combination with carbachol into the mPRF of intact unanesthetized cats. All of the G protein-altering compounds significantly reduced the ability of carbachol to produce the REM sleep-like state. Pertussis toxin caused the greatest decrease in the percent of time spent in the carbachol-evoked REM sleep-like state, showing for the first time mediation by a pertussis toxin-sensitive (Gi- or G(o)-like) G protein. Cholera toxin blocked the carbachol-induced respiratory depression, indicating mediation by a Gs-like G protein. Forskolin significantly decreased carbachol-evoked REM sleep. These data provide the first demonstration that adenylyl cyclase within the mPRF contributes to the carbachol induction of REM sleep and respiratory depression.

Medullary respiratory neuron activity: relationship to tonic and phasic REM sleep

1980 ◽  
Vol 48 (1) ◽  
pp. 54-65 ◽  
Author(s):  
J. Orem
Keyword(s):  
Brain Stem ◽  
Rem Sleep ◽  
Respiratory Activity ◽  
Regression Line ◽  
Respiratory Neurons ◽  
Neuron Activity ◽  
Respiratory Neuron ◽  
Dorsal Respiratory Group ◽  
Phasic Rem Sleep ◽  
The Relationship

This study analyzes the relationship of brain stem respiratory neuron activity to the tonic and phasic events of rapid-eye-movement (REM) sleep. Dorsal and ventral medullary respiratory neurons were recorded in sleeping cats. Discharges of inspiratory and expiratory cells increased in number and frequency with increases in pontogeniculooccipital (PGO) spiking (phasic REM activity). Across neurons the correlations between PGO wave frequency and respiratory neuron activity were positively related to the discharge levels of the neurons: the more active the cell, the greater the relationship to PGO activity. Tonic REM influences on respiratory neurons were calculated by extrapolating from the regression line relating PGO frequency and neuron activity to the hypothetical state of no PGO activity. These calculated levels, when compared to non-REM sleep levels, showed that tonic REM mechanisms reduced the activity of some neurons and activated others. Ventral medullary respiratory activity generally was decreased during tonic rem, whereas dorsal respiratory group cells were variously activated and inactivated. These results demonstrate an association of brain stem respiratory activity to nonrespiratory REM sleep variables.

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