Preoptic hypothalamic warming suppresses laryngeal dilator activity during sleep

Upper airway dilator activity during sleep appears to be diminished under conditions of enhanced sleep propensity, such as after sleep deprivation, leading to worsening of obstructive sleep apnea (OSA). Non-rapid eye movement (NREM) sleep propensity originates in sleep-active neurons of the preoptic area (POA) of the hypothalamus and is facilitated by activation of POA warm-sensitive neurons (WSNs). We hypothesized that activation of WSNs by local POA warming would inhibit activity of the posterior cricoarytenoid (PCA) muscle, an airway dilator, during NREM sleep. In chronically prepared unrestrained cats, the PCA exhibited inspiratory bursts in approximate synchrony with inspiratory diaphragmatic activity during waking, NREM, and REM. Integrated inspiratory PCA activity (IA), peak activity (PA), and the lead time (LT) of the onset of inspiratory activity in PCA relative to diaphragm were significantly reduced in NREM sleep and further reduced during REM sleep compared with waking. Mild bilateral local POA warming (0.5-1.2 degrees C) significantly reduced IA, PA, and LT during NREM sleep compared with a prewarming NREM baseline. In some animals, effects of POA warming on PCA activity were found during waking or REM. Because POA WSN activity is increased during spontaneous NREM sleep and regulates sleep propensity, we hypothesize that this activation contributes to reduction of airway dilator activity in patients with OSA.     

Rapid changes in glutamate levels in the posterior hypothalamus across sleep-wake states in freely behaving rats

The histamine-containing posterior hypothalamic region (PH-TMN) plays a key role in sleep-wake regulation. We investigated rapid changes in glutamate release in the PH-TMN across the sleep-wake cycle with a glutamate biosensor that allows the measurement of glutamate levels at 1- to 4-s resolution. In the PH-TMN, glutamate levels increased in active waking (AW) and rapid eye movement (REM) sleep compared with quiet waking and nonrapid eye movement (NREM) sleep. There was a rapid (0.6 +/- 1.8 s) and progressive increase in glutamate levels at REM sleep onset. A reduction in glutamate levels consistently preceded the offset of REM sleep by 8 +/- 3 s. Short-duration sleep deprivation resulted in a progressive increase in glutamate levels in the PH-TMN, perifornical-lateral hypothalamus (PF-LH), and cortex. We found that in the PF-LH, glutamate levels took a longer time to return to basal values compared with the time it took for glutamate levels to increase to peak values during AW onset. This is in contrast to other regions we studied in which the return to baseline values after AW was quicker than their rise with waking onset. In summary, we demonstrated an increase in glutamate levels in the PH-TMN with REM/AW onset and a drop in glutamate levels before the offset of REM. High temporal resolution measurement of glutamate levels reveals dynamic changes in release linked to the initiation and termination of REM sleep.     

The cognitive neuroscience of sleep: neuronal systems,consciousness and learning

Sleep can be addressed across the entire hierarchy of biological organization. We discuss neuronal-network and regional forebrain activity during sleep, and its consequences for consciousness and cognition. Complex interactions in thalamocortical circuits maintain the electroencephalographic oscillations of non-rapid eye movement (NREM) sleep. Functional neuroimaging affords views of the human brain in both NREM and REM sleep, and has informed new concepts of the neural basis of dreaming during REM sleep -- a state that is characterized by illogic, hallucinosis and emotionality compared with waking. Replay of waking neuronal activity during sleep in the rodent hippocampus and in functional images of human brains indicates possible roles for sleep in neuroplasticity. Different forms and stages of learning and memory might benefit from different stages of sleep and be subserved by different forebrain regions.     

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

Regional cerebral glucose metabolic rate in human sleep assessed by positron emission tomography

The cerebral metabolic rate of glucose was measured during nighttime sleep in 36 normal volunteers using positron emission tomography and fluorine-18-labeled 2-deoxyglucose (FDG). In comparison to waking controls, subjects given FDG during non-rapid eye movement (NREM) sleep (primarily stages 2 and 3) showed about a 23% reduction in metabolic rate across the entire brain. This decrease was greater for the frontal than temporal or occipital lobes, and greater for basal ganglia and thalamus than cortex. Subjects in rapid eye movement (REM) sleep tended to have higher cortical metabolic rates than waking subjects. The cingulate gyrus was the only cortical structure to show a significant increase in glucose metabolic rate in REM sleep in comparison to waking. The basal ganglia were relatively more active on the right in REM sleep and symmetrical in NREM sleep.     

Dialysis delivery of an adenosine A2A agonist into the pontine reticular formation of C57BL/6J mouse increases pontine acetylcholine release and sleep

In vivo microdialysis in C57BL/6J (B6) mouse was used to test the hypothesis that activating adenosine A(2A) receptors in the pontine reticular formation (PRF) increases acetylcholine (ACh) release and rapid eye movement (REM) sleep. Eight concentrations of the adenosine A(2A) receptor agonist 2-p-(2-carboxyethyl)phenethylamino-5'-N-ethylcarboxamidoadenosine hydrochloride (CGS 21680; CGS) were delivered to the PRF and ACh in the PRF was quantified. ACh release was significantly increased by dialysis with 3 mum CGS and significantly decreased by dialysis with 10 and 100 microm CGS. Co-administration of the adenosine A(2A) receptor antagonist 4-(2-[7-amino-2-(2-furyl)[1,2,4]triazolo[2,3-a][1,3,5]triazin-5-ylamino]ethyl)phenol (ZM 241385; 30 nM) blocked the CGS-induced increase in ACh release. In a second series of experiments, CGS (3 microm) was delivered by dialysis to the PRF for 2 h while recording sleep and wakefulness. CGS significantly decreased time in wakefulness (-51% in h 1; -54% in h 2), increased time in non-rapid eye movement (NREM) sleep (90% in h 1; 151% in h 2), and increased both time in REM sleep (331% in h 2) and the number of REM sleep episodes (488% in h 2). The enhancement of REM sleep is consistent with the interpretation that adenosine A(2A) receptors in the PRF of the B6 mouse contribute to REM sleep regulation, in part, by increasing ACh release in the PRF. A(2A) receptor activation may promote NREM sleep via GABAergic inhibition of arousal promoting neurons in the PRF.     

The maturational trajectories of NREM and REM sleep durations differ across adolescence on both school-night and extended sleep

We recorded sleep electroencephalogram longitudinally across ages 9-18 yr in subjects sleeping at home. Recordings were made twice yearly on 4 consecutive nights: 2 nights with the subjects maintaining their ongoing school-night schedules, and 2 nights with time in bed extended to 12 h. As expected, school-night total sleep time declined with age. This decline was entirely produced by decreasing non-rapid eye movement (NREM) sleep. Rapid eye movement (REM) sleep durations increased slightly but significantly. NREM and REM sleep durations also exhibited different age trajectories when sleep was extended. Both durations exceeded those on school-night schedules. However, the elevated NREM duration did not change with age, whereas REM durations increased significantly. We interpret the adolescent decline in school-night NREM duration in relation to our hypothesis that NREM sleep reverses changes produced in plastic brain systems during waking. The "substrate" produced during waking declines across adolescence, because synaptic elimination decreases the intensity (metabolic rate) of waking brain activity. Declining substrate reduces both NREM intensity (i.e., delta power) and NREM duration. The absence of a decline in REM sleep duration on school-night sleep and its age-dependent increase in extended sleep pose new challenges to understanding its physiological role. Whatever their ultimate explanation, these robust findings demonstrate that the two physiological states of human sleep respond differently to the maturational brain changes of adolescence. Understanding these differences should shed new light on both brain development and the functions of sleep.     

Cataplexy-active neurons in the hypothalamus: implications for the role of histamine in sleep and waking behavior

Noradrenergic, serotonergic, and histaminergic neurons are continuously active during waking, reduce discharge during NREM sleep, and cease discharge during REM sleep. Cataplexy, a symptom associated with narcolepsy, is a waking state in which muscle tone is lost, as it is in REM sleep, while environmental awareness continues, as in alert waking. In prior work, we reported that, during cataplexy, noradrenergic neurons cease discharge, and serotonergic neurons greatly reduce activity. We now report that, in contrast to these other monoaminergic "REM-off" cell groups, histamine neurons are active in cataplexy at a level similar to or greater than that in quiet waking. We hypothesize that the activity of histamine cells is linked to the maintenance of waking, in contrast to activity in noradrenergic and serotonergic neurons, which is more tightly coupled to the maintenance of muscle tone in waking and its loss in REM sleep and cataplexy.     

Upper airway resistance and geniohyoid muscle activity in normal men during wakefulness and sleep

Sleep-related reduction in geniohyoid muscular support may lead to increased airway resistance in normal subjects. To test this hypothesis, we studied seven normal men throughout a single night of sleep. We recorded inspiratory supraglottic airway resistance, geniohyoid muscle electromyographic (EMGgh) activity, sleep staging, and ventilatory parameters in these subjects during supine nasal breathing. Mean inspiratory upper airway resistance was significantly (P less than 0.01) increased in these subjects during all stages of sleep compared with wakefulness, reaching highest levels during non-rapid-eye-movement (NREM) sleep [awake 2.5 +/- 0.6 (SE) cmH2O.l-1.s, stage 2 NREM sleep 24.1 +/- 11.1, stage 3/4 NREM sleep 30.2 +/- 12.3, rapid-eye-movement (REM) sleep 13.0 +/- 6.7]. Breath-by-breath linear correlation analyses of upper airway resistance and time-averaged EMGgh amplitude demonstrated a significant (P less than 0.05) negative correlation (r = -0.44 to -0.55) between these parameters in five of seven subjects when data from all states (wakefulness and sleep) were combined. However, we found no clear relationship between normalized upper airway resistance and EMGgh activity during individual states (wakefulness, stage 2 NREM sleep, stage 3/4 NREM sleep, and REM sleep) when data from all subjects were combined. The timing of EMGgh onset relative to the onset of inspiratory airflow did not change significantly during wakefulness, NREM sleep, and REM sleep. Inspiratory augmentation of geniohyoid activity generally preceded the start of inspiratory airflow. The time from onset of inspiratory airflow to peak inspiratory EMGgh activity was significantly increased during sleep compared with wakefulness (awake 0.81 +/- 0.04 s, NREM sleep 1.01 +/- 0.04, REM sleep 1.04 +/- 0.05; P less than 0.05). These data indicate that sleep-related changes in geniohyoid muscle activity may influence upper airway resistance in some subjects. However, the relationship between geniohyoid muscle activity and upper airway resistance was complex and varied among subjects, suggesting that other factors must also be considered to explain sleep influences on upper airway patency.     

Occlusion pressure and ventilation during sleep in normal humans

Previous investigation in normal humans has demonstrated reduced ventilation and ventilatory responses to chemical stimuli during sleep. Most have interpreted this to be a product of decreasing central nervous system sensitivity to the normal stimuli that maintain ventilation, whereas other factors such as increasing airflow resistance could also contribute to this reduction in respiration. To improve our understanding of these events, we measured ventilation and occlusion pressures (P0.1) during unstimulated ventilation and rebreathing-induced hypercapnia during wakefulness and non-rapid-eye-movement (NREM) and rapid-eye-movement (REM) sleep. Eighteen subjects (10 males and 8 females) of whom seven were snorers (5 males and 2 females) were studied. Ventilation was reduced during both NREM and REM sleep (P less than 0.05), but this decrement in minute ventilation tended to be greater in snorers than nonsnorers. Unstimulated P0.1, on the other hand, was maintained or increased during sleep in all groups studied, with males and snorers showing the largest increase. The hypercapnic ventilatory response fell during both NREM and REM sleep and tended to be lower during REM than NREM sleep. However, the P0.1 response to hypercapnia during NREM sleep was well maintained at the waking level although the REM response was statistically reduced. These studies suggest that the mechanism of the reduction in ventilation and the hypercapnic ventilatory response seen during sleep, particularly NREM sleep, is likely to be multifactorial and not totally a product of decreasing central respiratory drive.     

Effect of sleep stage on breathing in children with central hypoventilation.

The early literature suggests that hypoventilation in infants with congenital central hypoventilation syndrome (CHS) is less severe during rapid eye movement (REM) than during non-REM (NREM) sleep. However, this supposition has not been rigorously tested, and subjects older than infancy have not been studied. Given the differences in anatomy, physiology, and REM sleep distribution between infants and older children, and the reduced number of limb movements during REM sleep, we hypothesized that older subjects with CHS would have more severe hypoventilation during REM than NREM sleep. Nine subjects with CHS, aged (mean +/- SD) 13 +/- 7 yr, were studied. Spontaneous ventilation was evaluated by briefly disconnecting the ventilator under controlled circumstances. Arousal was common, occurring in 46% of REM vs. 38% of NREM trials [not significant (NS)]. Central apnea occurred during 31% of REM and 54% of NREM trials (NS). Although minute ventilation declined precipitously during both REM and NREM trials, hypoventilation was less severe during REM (drop in minute ventilation of 65 +/- 23%) than NREM (drop of 87 +/- 16%, P = 0.036). Despite large changes in gas exchange during trials, there was no significant change in heart rate during either REM or NREM sleep. We conclude that older patients with CHS frequently have arousal and central apnea, in addition to hypoventilation, when breathing spontaneously during sleep. The hypoventilation in CHS is more severe during NREM than REM sleep. We speculate that this may be due to increased excitatory inputs to the respiratory system during REM sleep.     

Abdominal muscle activity during CO2 rebreathing in sleeping neonates

Comparison of the abdominal muscle response to CO2 rebreathing in rapid-eye-movement (REM) and non-REM (NREM) sleep was performed in healthy premature infants near full term. Eight subjects were studied at a postconceptional age of 40 +/- 1.6 (SD) wk (range 38-43 wk) during spontaneous sleep. Sleep stages were defined on the basis of electrophysiological and behavioral criteria, and diaphragmatic and abdominal muscle electromyographic activity was recorded by cutaneous electrodes. The responses to CO2 were measured by a modified Read rebreathing technique. The minute ventilation and diaphragmatic and abdominal muscle electromyographic activities were calculated and plotted against end-tidal CO2 partial pressure. Both the ventilatory and diaphragmatic muscle responses to CO2 decreased from NREM to REM sleep (P less than 0.05). Abdominal muscles were forcefully recruited in response to CO2 rebreathing during NREM sleep. In REM sleep, abdominal muscle response to CO2 was virtually absent or decreased compared with NREM sleep (P less than 0.05). We conclude that 1) the abdominal muscles are recruited during NREM sleep in response to CO2 rebreathing in healthy premature infants near full term and 2) the abdominal muscle recruitment is inhibited during REM sleep compared with NREM sleep, and this REM sleep-related inhibition probably contributes to the decrease in the ventilatory response to CO2 rebreathing in REM sleep.     

Relationship between renal sympathetic nerve activity and renal blood flow during natural behavior in rats

The purpose of the present study was to determine the relationship between renal sympathetic nerve activity (RSNA) and renal blood flow (RBF) during normal daily activity in conscious, chronically instrumented Wistar rats (n = 8). The animal's behavior was classified as rapid eye movement (REM) sleep, non-REM (NREM) sleep, quiet awake, moving, and grooming states. On average RSNA was lowest during REM sleep, which was decreased by 39.0 +/- 3.2% (P < 0.05) relative to NREM sleep, and rose linearly with an increase in activity level in the order of quiet awake (by 10.9 +/- 1.8%, P < 0.05), moving (by 29.4 +/- 2.9%, P < 0.05), and grooming (by 65.3 +/- 3.9%, P < 0.05) relative to NREM sleep. By contrast, RBF was highest during REM sleep, which was increased by 4.8 +/- 0.7% (P < 0.05) relative to NREM sleep and decreased significantly (P < 0.05) by 5.5 +/- 0.6 and 6.6 +/- 0.5% during moving and grooming states, respectively, relative to NREM sleep. There was a significant (P < 0.05) inverse linear relationship between the percent changes in RSNA and RBF and between those in RSNA and renal vascular conductance. Furthermore, renal denervation (n = 8) abolished the changes in RBF induced by different natural behavioral activities. These results suggest that the changes in RSNA induced by natural behavioral activities had a significant influence on RBF.     

Ventilatory behavior during sleep among A/J and C57BL/6J mouse strains.

The pattern of breathing during sleep could be a heritable trait. Our intent was to test this genetic hypothesis in inbred mouse strains known to vary in breathing patterns during wakefulness (Han F, Subramanian S, Dick TE, Dreshaj IA, and Strohl KP. J Appl Physiol 91: 1962-1970, 2001; Han F, Subramanian S, Price ER, Nadeau J, and Strohl KP, J Appl Physiol 92: 1133-1140, 2002) to determine whether such differences persisted into non-rapid eye movement (NREM) and rapid eye movement (REM) sleep. Measures assessed in C57BL/6J (B6; Jackson Laboratory) and two A/J strains (A/J Jackson and A/J Harlan) included ventilatory behavior [respiratory frequency, tidal volume, minute ventilation, mean inspiratory flow, and duty cycle (inspiratory time/total breath time)], and metabolism, as performed by the plethsmography method with animals instrumented to record EEG, electromyogram, and heart rate. In all strains, there were reductions in minute ventilation and CO2 production in NREM compared with wakefulness (P < 0.001) and a further reduction in REM compared with NREM (P < 0.001), but no state-by-stain interactions. Frequency showed strain (P < 0.0001) and state-by-strain interactions (P < 0.0001). The A/J Jackson did not change frequency in REM vs. NREM [141 +/- 15 (SD) vs. 139 +/- 14 breaths/min; P = 0.92], whereas, in the A/J Harlan, it was lower in REM vs. NREM (168 +/- 14 vs. 179 +/- 12 breaths/min; P = 0.0005), and, in the B6, it was higher in REM vs. NREM (209 +/- 12 vs. 188 +/- 13 breaths/min; P < 0.0001). Heart rate exhibited strain (P = 0.003), state (P < 0.0001), and state-by-strain interaction (P = 0.017) and was lower in NREM sleep in the A/J Harlan (P = 0.035) and B6 (P < 0.0001). We conclude that genetic background affects features of breathing during NREM and REM sleep, despite broad changes in state, metabolism, and heart rate.     

Biogenic amines in the regulation of wakefulness and sleep

Neurophysiological, neurochemical and neuropharmacological evidence indicates that cerebral monoamines are important regulators of wakefulness and sleep besides cerebral amino acid-ergic and peptidergic systems. The cerebral monoamines noradrenaline, dopamine and acetylcholine are positively involved in electroencephalographic aspects of waking and paradoxical or REM sleep. A high level of noradrenergic transmission facilitates waking, and a lower, moderate level facilitates REM sleep. Serotonin is involved in the regulation of synthesis, storage and release of sleep inducing factors, and in the gating mechanisms of REM sleep. Histamine neurons play a role in the regulation of vigilance during waking state. These neurotransmitter systems are important targets for drug actions.     

Elicited pontogeniculooccipital waves and phasic suppression of diaphragm activity in sleep and wakefulness

Fractionations are 20- to 100-ms pauses indiaphragm activity that occur spontaneously during rapid-eye-movement(REM) sleep, sometimes in association with pontogeniculooccipital (PGO)waves. Auditory stimuli can elicit fractionations or PGOwaves during REM sleep, non-REM (NREM) sleep, and waking; however,their interrelationship has not been investigated. To determine whetherthe two phenomena are produced by a common phasic-event generator inREM sleep, we examined PGO waves and fractionations that were elicitedby auditory stimuli (tones) presented to freely behaving cats across states. Tones elicited PGO waves and two types of fractionations: short-latency fractionation responses (SFRs; 10- to 60-ms latencies) and long-latency fractionation responses (LFRs; 60- to 120-ms latencies). Both a PGO wave and a SFR were elicited in60-70% of trials across states, but each could be elicited alone.The latencies and durations of elicited SFRs were similar acrossstates, but the latencies of elicited PGO waves in REM sleep (mean 62.5 ms) were significantly longer than in waking or NREM sleep. Elicited SFRs consistently occur with shorter latencies than do PGO waves, incontrast to spontaneous fractionations, which have a variable relationship to PGO waves and usually occur 10-40 ms after the onset of the PGO wave. The LFR then, elicited mostfrequently during REM sleep, resembles a spontaneous fractionation inits temporal relationship to the PGO wave and may reflect the bias toward motoneuronal inhibition characterizing REM sleep but not NREMsleep or waking. We conclude that, although PGO waves and SFRs sharesome features, like LFRs they probably are generated by differentneuronal populations. In three cats there was no correlation betweenPGO waves and fractionations, whereas in one cat they were associatedin REM sleep (LFRs and SFRs) and waking (SFRs only). Thus the majorityof evidence argues against the existence of a common phasic-eventgenerator in REM sleep.

     

Salubrinal, an inhibitor of protein synthesis, promotes deep slow wave sleep

Previous work showed that sleep is associated with increased brain protein synthesis and that arrest of protein synthesis facilitates sleep. Arrest of protein synthesis is induced during the endoplasmic reticulum (ER) stress response, through phosphorylation of eukaryotic initiation factor 2alpha (p-eIF2alpha). We tested a hypothesis that elevation of p-eIF2alpha would facilitate sleep. We studied the effects of intracerebroventricular infusion of salubrinal (Salub), which increases p-eIF2alpha by inhibiting its dephosphorylation. Salub increased deep slow wave sleep by 255%, while reducing active waking by 49%. Delta power within non-rapid eye movement (NREM) sleep was increased, while power in the sigma, beta, and gamma bands during NREM was reduced. We found that Salub increased expression of p-eIF2alpha in the basal forebrain (BF) area, a sleep-wake regulatory brain region. Therefore, we quantified the p-eIF2alpha-immunolabeled neurons in the BF area; Salub administration increased the number of p-eIF2alpha-expressing noncholinergic neurons in the caudal BF. In addition, Salub also increased the intensity of p-eIF2alpha expression in both cholinergic and noncholinergic neurons, but this was more widespread among the noncholinergic neurons. Our findings support a hypothesis that sleep is facilitated by signals associated with the ER stress response.     

Formation and Dynamics of Waves in a Cortical Model of Cholinergic Modulation

Acetylcholine (ACh) is a regulator of neural excitability and one of the neurochemical substrates of sleep. Amongst the cellular effects induced by cholinergic modulation are a reduction in spike-frequency adaptation (SFA) and a shift in the phase response curve (PRC). We demonstrate in a biophysical model how changes in neural excitability and network structure interact to create three distinct functional regimes: localized asynchronous, traveling asynchronous, and traveling synchronous. Our results qualitatively match those observed experimentally. Cortical activity during slow wave sleep (SWS) differs from that during REM sleep or waking states. During SWS there are traveling patterns of activity in the cortex; in other states stationary patterns occur. Our model is a network composed of Hodgkin-Huxley type neurons with a M-current regulated by ACh. Regulation of ACh level can account for dynamical changes between functional regimes. Reduction of the magnitude of this current recreates the reduction in SFA the shift from a type 2 to a type 1 PRC observed in the presence of ACh. When SFA is minimal (in waking or REM sleep state, high ACh) patterns of activity are localized and easily pinned by network inhomogeneities. When SFA is present (decreasing ACh), traveling waves of activity naturally arise. A further decrease in ACh leads to a high degree of synchrony within traveling waves. We also show that the level of ACh determines how sensitive network activity is to synaptic heterogeneity. These regimes may have a profound functional significance as stationary patterns may play a role in the proper encoding of external input as memory and traveling waves could lead to synaptic regularization, giving unique insights into the role and significance of ACh in determining patterns of cortical activity and functional differences arising from the patterns.     

Sleep and cortical temperature in the Djungarian hamster under baseline conditions and after sleep deprivation

The Djungarian hamster (Phodopus sungorus) is a markedly photoperiodic rodent which exhibits daily torpor under short photoperiod. Normative data were obtained on vigilance states, electroencephalogram (EEG) power spectra (0.25–25.0 Hz), and cortical temperature (T_CRT) under a 168 h light-dark schedule, in 7 Djungarian hamsters for 2 baseline days, 4 h sleep deprivation (SD) and 20 h recovery.During the baseline days total sleep time amounted to 59% of recording time, 67% in the light period and 43% in the dark period. The 4 h SD induced a small increase in the amount of non-rapid eye movement (NREM) sleep and a marked increase in EEG slow-wave activity (SWA; mean power density 0.75–4.0 Hz) within NREM sleep in the first hours of recovery. T_CRT was lower in the light period than in the dark period. It decreased at transitions from either waking or rapid eye movement (REM) sleep to NREM sleep, and increased at the transition from NREM sleep to waking or REM sleep. After SD, T_CRT was lower in all vigilance states.In conclusion, the sleep-wake pattern, EEG spectrum, and time course of T_CRT in the Djungarian hamster are similar to other nocturnal rodents. Also in the Djungarian hamster the time course of SWA seems to reflect a homeostatically regulated process as was formulated in the two-process model of sleep regulation.Abbreviations EEG electroencephalogram - EMG electromyogram - N NREM sleep - NREM non-rapid eye movement - R REM sleep - REM rapid eye movement - SD sleep deprivation - SWA slow-wave activity - T_CRT cortical temperature - TST total sleep time - VS vigilance state - W waking     

Development of CO2 sensitivity: effects of gestational age, postnatal age, and sleep state

To determine the independent effects of sleep state, gestational age, and postnatal age on eucapnic ventilation and steady-state CO2 sensitivity, nine premature (146 +/- 3 days) and eight full-term (168 +/- 2 days) monkeys, Macaca nemestrina, from accurately timed conceptions were studied serially over the first 3 wk of life. Minute volume (VE)/kg,tidal volume (VT)/kg, and respiratory frequency were quantitated during rapid-eye-movement sleep (REM) and nonrapid-eye-movement sleep (NREM)in room air and when animals were breathing varied concentrations of cO2 in 21% O2. Eucapnic VE/kg and CO2 sensitivity [(deltaVE/kg)/delta PaCO2] increased progressively with advancing postnatal age during NREM sleep in grouped term and premature animals. CO2 sensitivity was not significantly different between REM and NREM sleep except in full-term animals at the highest postconceptual age studied (189 +/- 2 days) when [(delta VE/kg)/delta PaCO2] was lower in REM sleep than in NREM sleep (209 +/- 54 vs. 301 +/- 71 ml.min-1.kg-1.Torr-1; P less than 0.05, paired-t test). Gestational age had no measurable effect on eucapnic ventilation or CO2 sensitivity. These results support the hypothesis that REM sleep-induced depression of CO2 sensitivity develops in the neonatal monkey with advancing postconceptual age.