CO2 dialysis in the medullary raphe of the rat increases ventilation in sleep

Central chemoreceptors are widespread within the brain stem. We hypothesize that function at different sites varies with arousal state. In unanesthetized rats, we produced focal acidification at single sites by means of microdialysis using artificial cerebrospinal fluid equilibrated with 25% CO2. Tissue acidosis, measured under anesthesia, is equivalent to that observed with 63 Torr end-tidal Pco 2 and is limited to 600 μm. Focal acidification of the retrotrapezoid nucleus increased ventilation by 24% only in wakefulness via an increase in tidal volume (Li A, Randall M, and Nattie E. J Appl Physiol 87: 910–919, 1999). In this study of the medullary raphe, the effect of such focal acidification was in sleep (defined by electroencephalographic and electromyographic criteria): ventilation and frequency increased by 15–20% in non-rapid eye movement sleep, and frequency increased by 15% in rapid eye movement sleep. There was no effect in wakefulness. Chemoreception in the medullary raphe appears to be responsive in sleep. Central chemoreceptors at two different locations appear to vary in effectiveness with arousal state.

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Effects of sleep-promoting factor from human urine on sleep cycle of cats

AJP Endocrinology and Metabolism ◽

10.1152/ajpendo.1981.241.4.e269 ◽

1981 ◽

Vol 241 (4) ◽

pp. E269-E274

Author(s):

J. E. Garcia-Arraras

Keyword(s):

Cerebrospinal Fluid ◽

Eye Movement ◽

Slow Wave ◽

Human Urine ◽

Slow Wave Sleep ◽

Sleep Cycle ◽

Rapid Eye Movement ◽

Rapid Eye Movement Sleep ◽

Artificial Cerebrospinal Fluid ◽

Normal Sleep

Slow-wave sleep (SWS) and rapid-eye-movement sleep (REM) were recorded in cats for 32 h a) under control conditions, b) following intraventricular infusions of artificial cerebrospinal fluid (CSF), and c) following infusions of sleep-promoting factor S prepared from human urine (SPU). During the first 12 h after receiving artificial CSF, the cats slept 4.9 +/- 0.2 h in slow-wave sleep (SWS) and 1.4 +/- 0.1 h in REM. Similar values were obtained from the same cats under control conditions. After infusions of SPU, the duration of SWS in the same cats increased to an average of 6.9 +/- 0.5 h with no significant change in REM averaged over 12 h; a transient decrease of REM in the first 4 h was fully compensated in subsequent hours. The increased SWS induced by the sleep-promoting factor from human urine subsided after 12 h, and there was no compensatory increase in wakefulness during the subsequent 20 h. The normal sleep cycle was not affected. In cats, therefore, the primary effect of SPU is to increase normal SWS, with little effect on REM.

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Transient attenuation of CO2 sensitivity after neurotoxic lesions in the medullary raphe area of awake goats

Journal of Applied Physiology ◽

10.1152/japplphysiol.00584.2004 ◽

2004 ◽

Vol 97 (6) ◽

pp. 2236-2247 ◽

Cited By ~ 39

Author(s):

M. R. Hodges ◽

C. Opansky ◽

B. Qian ◽

S. Davis ◽

J. Bonis ◽

...

Keyword(s):

Eye Movement ◽

Glutamate Receptor ◽

Tryptophan Hydroxylase ◽

Ibotenic Acid ◽

Control Mechanisms ◽

Rapid Eye Movement ◽

Rapid Eye Movement Sleep ◽

Medullary Raphe ◽

Before And After ◽

Neurokinin 1

The major objective of this study was to gain insight into whether under physiological conditions medullary raphe area neurons influence breathing through CO2/H+ chemoreceptors and/or through a postulated, nonchemoreceptor modulatory influence. Microtubules were chronically implanted into the raphe of adult goats ( n = 13), and breathing at rest (awake and asleep), breathing during exercise, as well as CO2 sensitivity were assessed repeatedly before and after sequential injections of the neurotoxins saporin conjugated to substance P [SP-SAP; neurokinin-1 receptor (NK1R) specific] and ibotenic acid (IA; nonspecific glutamate receptor excitotoxin). In all goats, microtubule implantation alone resulted in altered breathing periods, manifested as central or obstructive apneas, and fractionated breathing. The frequency and characteristics of the altered breathing periods were not subsequently affected by injections of the neurotoxins ( P > 0.05). Three to seven days after SP-SAP or subsequent IA injection, CO2 sensitivity was reduced ( P < 0.05) by 23.8 and 26.8%, respectively, but CO2 sensitivity returned to preinjection control values >7 days postinjection. However, there was no hypoventilation at rest (awake, non-rapid eye movement sleep, or rapid eye movement sleep) or during exercise after these injections ( P > 0.05). The neurotoxin injections resulted in neuronal death greater than three times that with microtubule implantation alone and reduced ( P < 0.05) both tryptophan hydroxylase-expressing (36%) and NK1R-expressing (35%) neurons at the site of injection. We conclude that both NK1R- and glutamate receptor-expressing neurons in the medullary raphe nuclei influence CO2 sensitivity apparently through CO2/H-expressing chemoreception, but the altered breathing periods appear unrelated to CO2 chemoreception and thus are likely due to non-chemoreceptor-related neuromodulation of ventilatory control mechanisms.

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The sleep-wake cycle and motor activity, but not temperature, are disrupted over the light-dark cycle in mice genetically depleted of serotonin

AJP Regulatory Integrative and Comparative Physiology ◽

10.1152/ajpregu.00400.2014 ◽

2015 ◽

Vol 308 (1) ◽

pp. R10-R17 ◽

Cited By ~ 18

Author(s):

Julia Z. Solarewicz ◽

Mariana Angoa-Perez ◽

Donald M. Kuhn ◽

Jason H. Mateika

Keyword(s):

Motor Activity ◽

Eye Movement ◽

Tryptophan Hydroxylase ◽

Paradoxical Sleep ◽

Core Body Temperature ◽

Light Cycle ◽

Rapid Eye Movement ◽

Rapid Eye Movement Sleep ◽

Dark Cycle ◽

Arousal State

We examined the role that serotonin has in the modulation of sleep and wakefulness across a 12-h:12-h light-dark cycle and determined whether temperature and motor activity are directly responsible for potential disruptions to arousal state. Telemetry transmitters were implanted in 24 wild-type mice (Tph2+/+) and 24 mice with a null mutation for tryptophan hydroxylase 2 (Tph2−/−). After surgery, electroencephalography, core body temperature, and motor activity were recorded for 24 h. Temperature for a given arousal state (quiet and active wake, non-rapid eye movement, and paradoxical sleep) was similar in the Tph2+/+ and Tph2−/− mice across the light-dark cycle. The percentage of time spent in active wakefulness, along with motor activity, was decreased in the Tph2+/+ compared with the Tph2−/− mice at the start and end of the dark cycle. This difference persisted into the light cycle. In contrast, the time spent in a given arousal state was similar at the remaining time points. Despite this similarity, periods of non-rapid-eye-movement sleep and wakefulness were less consolidated in the Tph2+/+ compared with the Tph2−/− mice throughout the light-dark cycle. We conclude that the depletion of serotonin does not disrupt the diurnal variation in the sleep-wake cycle, motor activity, and temperature. However, serotonin may suppress photic and nonphotic inputs that manifest at light-dark transitions and serve to shorten the ultraradian duration of wakefulness and non-rapid-eye-movement sleep. Finally, alterations in the sleep-wake cycle following depletion of serotonin are unrelated to disruptions in the modulation of temperature.

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CO2 dialysis in nucleus tractus solitarius region of rat increases ventilation in sleep and wakefulness

Journal of Applied Physiology ◽

10.1152/japplphysiol.01128.2001 ◽

2002 ◽

Vol 92 (5) ◽

pp. 2119-2130 ◽

Cited By ~ 107

Author(s):

Eugene E. Nattie ◽

Aihua Li

Keyword(s):

Cerebrospinal Fluid ◽

Tidal Volume ◽

Nucleus Tractus Solitarius ◽

Ventilation Frequency ◽

Retrotrapezoid Nucleus ◽

Naturally Occurring ◽

Central Chemoreceptors ◽

Artificial Cerebrospinal Fluid ◽

Medullary Raphe ◽

Stimulation Of

To evaluate the function of widely distributed central chemoreceptors during sleep and wakefulness in the rat, we focally stimulate single chemoreceptor sites during naturally occurring sleep-wake cycles by microdialysis of artificial cerebrospinal fluid equilibrated with 25% CO2. In retrotrapezoid nucleus, this increased ventilation (tidal volume) by 24% only in wakefulness (Li A, Randall M, and Nattie E. J Appl Physiol 87: 910–919, 1999). In caudal medullary raphé, it increased ventilation (frequency) by 15–20% only in sleep (Nattie EE and Li A. J Appl Physiol 90: 1247–1257, 2001). Here, in nucleus tractus solitarius (NTS), focal acidification significantly increased ventilation by 11% in sleep and 7% in wakefulness rostrally ( n = 5) and by 16% in sleep and 28% in wakefulness caudally ( n = 5). The sleep-wake cycle was unaltered. Dialysis with 5% CO2 had no effect. Dialysis with 50% CO2 caudally did not further stimulate ventilation but did disrupt sleep. Central chemoreceptors in the NTS affect breathing in both sleep and wakefulness. The threshold for arousal in caudal NTS is greater than that for the stimulation of breathing.

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