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D McGinty

Publications and source records attributed to D McGinty.

At least 37 records · Page 2Linked to original sources
PubMed1998

Sleep-waking discharge patterns of ventrolateral preoptic/anterior hypothalamic neurons in rats.

Numerous lesion, stimulation and recording studies in experimental animals demonstrate the importance of neurons within the preoptic/anterior hypothalamic area (POA) in the regulation of sleep induction and sleep maintenance. Recently, a discrete cluster of cells in the ventrolateral POA (vlPOA) of rats was found to exhibit elevated c-fos gene expression during sleep, indicating that these neurons are strongly activated during nonREM and/or REM sleep stages. We examined neuronal discharge during wakefulness and sleep throughout the dorsal to ventral extent of the lateral POA in rats, using chronic microwire technique. We found that neurons with elevated discharge rates during sleep, compared to waking, were localized to the vlPOA. As a group, vlPOA neurons displayed elevated discharge rates during both nonREM and REM sleep. Discharge of vlPOA neurons reflected the depth of sleep, i.e., discharge rates increased significantly from light to deep nonREM sleep. During recovery sleep following 12-14 h of sleep deprivation, vlPOA neurons displayed increased sleep-related discharge, compared to baseline sleep. Neurons in the vlPOA displaying increased neuronal discharge during sleep were located in the same area where neurons exhibit increased c-fos gene expression during sleep. Such neurons are likely components of a rostral hypothalamic mechanism that regulates sleep onset and sleep maintenance.

Animals↗
PubMed1997

Thermosensitive neurons of the diagonal band in rats: relation to wakefulness and non-rapid eye movement sleep.

The thermosensitivity of the neurons in the diagonal band of Broca (DBB) was studied in 12 freely moving rats by determining responses to local cooling or warming with a water perfused thermode. Of 151 neurons studied, 37 (25%) neurons met the criterion for thermosensitivity including 17 warm-sensitive (WSNs) and 20 cold-sensitive neurons (CSNs). The spontaneous discharge rates of WSNs and CSNs were recorded through 1-3 sleep-waking cycles. The discharge of WSNs and CSNs during waking and non-rapid eye movement (NREM) sleep were different. Of 17 WSNs, 10 exhibited increased discharge rates during NREM sleep as compared with waking (NREM/Wake discharge ratio, > 1.2). Of 20 CSNs, 14 discharged more slowly during NREM sleep as compared with waking (NREM/Wake discharge ratio, < 0.8). In both WSNs and CSNs, changes in discharge rate preceded EEG changes at the waking-NREM transition. These results support a hypothesis that the activation of sleep-related WSNs and the deactivation of wake-related CSNs play a role in the onset and regulation of NREM sleep.

Animals↗
PubMed1997

The effects of temperature and synaptic blockade in vitro on neurons of the horizontal limb of the diagonal band of Broca in the rat basal forebrain.

We studied the thermosensitivity of neurons in the rat horizontal limb of the diagonal band of Broca (HDB) in vitro under normal conditions and under conditions of a low calcium/high magnesium synaptic blockade (SB). Of 52 HDB neurons tested, 34 neurons (65%) were warm-sensitive (WS), three neurons (6%) were cold-sensitive (CS), 11 neurons (21%) were temperature-insensitive (TI) and four additional neurons (8%) were both warm- and cold-sensitive (WS/CS). Of 34 neurons tested for thermosensitivity under SB, 11 were WS, 4 were CS and 19 were TI. Nearly half (48%) of the WS neurons maintained warm sensitivity under SB, 43% became TI and 9% became CS. Baseline firing rates of neurons significantly decreased during SB and then increased during recovery from SB. In addition, a distinct anatomical distribution of thermosensitive neurons was found in the HDB. The most ventral aspect of the HDB (interaural +0.9-1.3 mm) had proportionally fewer temperature sensitive neurons (65% vs. 88%) than areas more dorsal (interaural +1.3-1.7 mm), and only one of seven ventral HDB neurons (14%) remained thermosensitive during SB. In the dorsal HDB, 65% of the neurons maintained thermosensitivity during SB. These results demonstrate that the HDB contains inherently thermosensitive neurons, and that a difference in thermal characteristics exists between the ventral and dorsal HDB neurons.

Action Potentials↗
PubMed1996

Preoptic/anterior hypothalamic neurons: thermosensitivity in wakefulness and non rapid eye movement sleep.

Thermosensitive neurons of the preoptic/anterior hypothalamic area (POAH) have been implicated in the regulation of both body temperature and non rapid eye movement (NREM) sleep. During NREM sleep, a majority of POAH warm-sensitive neurons (WSN) exhibit increased discharge compared to wakefulness. Cold-sensitive neurons (CSN) exhibit reduced discharge in NREM sleep compared to wakefulness. To further study the mechanism underlying these processes, the present study compared discharge rate and thermosensitivity (discharge rate change/degree C) of WSNs and CSNs in NREM sleep and wakefulness in freely moving adult cats. The thermosensitivity of 24 WSNs and 31 CSNs from the medial POAH was determined from responses to local POAH warming and cooling. WSNs with increased discharge in NREM sleep exhibited increased thermosensitivity during NREM sleep compared to wakefulness. CSNs with decreased discharge during NREM sleep exhibited decreased thermosensitivity in NREM sleep. The change in thermosensitivity from wakefulness to NREM sleep was correlated with the change in discharge rate in WSNs but not in CSNs. In addition, 9 of 47 neurons that were thermo-insensitive during wakefulness became warm-sensitive during NREM sleep. Changes in POAH neuronal thermosensitivity could be a component of the mechanism for stabilization of state after state transition.

Animals↗
PubMed1996

Brainstem stimulation during sleep evokes abnormal rhythmic activity in thalamic neurons in feline penicillin epilepsy.

Some periods in the sleep-waking cycle are more seizure prone than others. In absence epilepsy, transition periods between nonrapid-eye-movement (nonREM) sleep and waking or REM sleep can be more seizure prone that stable states. One feature of transition periods that is hypothesized to promote seizure activity is the presence of coincident activity in ascending brainstem reticular formation (RF) arousal systems with synchronized thalamo-cortical activity. To evaluate this hypothesis we examined the state-dependent effects of low intensity RF stimulation on thalamic single unit activity in control conditions and following systemic penicillin-G administration to adult cats. In control conditions, RF stimulation during waking and REM sleep typically evoked a short-latency action potential in thalamic neurons. The same stimulation during nonREM sleep commonly evoked a high frequency burst of action potentials followed by a period of suppressed discharge. In 16/26 neurons, a second rebound burst of action potentials followed the period of discharge suppression. The average interval between the initial and rebound bursts was 75.1 +/- 6.0 ms, which was similar to the interburst interval recorded in these same cells during spontaneous EEG spindles. Following administration of penicillin-G, RF stimulation during nonREM sleep evoked high frequency burst firing, followed by 1-2 rebound bursts in 21/22 thalamic neurons. The average evoked interburst interval was 152.5 +/- 7.3 ms, a value comparable to the interburst interval displayed by these same cells during spontaneous spike-wave seizure activity (157.8 +/- 8.7 ms). RF-evoked rhythmic discharges were dependent upon the presence of thalamocortical synchronization, as responses evoked during waking and REM sleep in penicillin treated cats were similar to those observed in control conditions.

Animals↗
PubMed1995

Local preoptic/anterior hypothalamic warming alters spontaneous and evoked neuronal activity in the magno-cellular basal forebrain.

Local warming of the medial preoptic/anterior hypothalamus (POAH) promotes sleep, enhances EEG slow-wave activity during sleep, and suppresses arousal-related discharge in neurons of the midbrain reticular formation (MRF) and the posterior lateral hypothalamic area (PLHa). Another important site of sleep and arousal regulation, and a potential site of POAH thermal modulation, is the magnocellular basal forebrain (BF). We examined the ability of local POAH warming during wakefulness to influence the spontaneous and evoked discharge of neurons recorded in the BF of unanesthetized, unrestrained cats. Seventy of 174 BF neurons responded to 60-90 s periods of POAH warming with either increases or decreases in discharge rate. Forty-one of the 70 responsive cells displayed suppression of waking discharge during warming. Discharge rate in these cells declined by an average of 26.04 +/- 2.76%/degrees C of POAH temperature increase. The majority of warming-suppressed BF cells (73%) displayed higher rates of discharge during periods of wakefulness compared to periods of sleep. Twenty-nine of 70 responsive cells responded to POAH warming with an average increase in discharge rate of 43.81 +/- 6.26%/degrees C. A majority of these neurons (62%) exhibited higher spontaneous discharge rates during sleep compared to waking. Orthodromic excitatory responses were evoked in 29 BF cells by electrical stimulation of the MRF or PLHa. Thirteen of 29 cells displayed a waking-related discharge pattern, and responded to POAH warming with a significant suppression of evoked excitation. For a group of 15 behavioral state-indifferent cells (i.e., cells displaying no modulation of spontaneous discharge rate across the sleep-waking cycle), POAH warming had no effect on evoked excitatory responses. These results support the hypothesis that thermosensitive neurons of the POAH exert control of sleep-waking state, in part, via modulation of arousal- and sleep-regulating cell types within the magnocellular BF.

Animals↗
PubMed1995

Neuronal discharge of preoptic/anterior hypothalamic thermosensitive neurons: relation to NREM sleep.

Thermosensitive neurons of the preoptic/anterior hypothalamic area (POAH) have been implicated in the regulation of non-rapid eye movement (NREM) sleep. We attempted to identify those medial POAH thermosensitive neurons that may be involved in NREM sleep regulation. The thermosensitivity of medial POAH neurons was studied in five freely moving adult cats by local cooling or warming of the medial POAH with a water-perfused thermode. Of 308 neurons, 65 (21%) were classified as thermosensitive, including 31 (10%) warm-sensitive and 34 (11%) cold-sensitive neurons. The spontaneous discharge rates of 28 warm-sensitive, 34 cold-sensitive, and 115 randomly selected thermoinsensitive neurons were recorded through one to three sleep-waking cycles. Patterns of spontaneous activity for warm- and cold-sensitive neurons were different. Of 28 warm-sensitive neurons, 18 (64%) exhibited increased discharge rate during NREM sleep compared with waking (NREM/wake, > or = 1.2). This subpopulation of warm-sensitive neurons also exhibited significantly increased thermosensitivity when tested during NREM sleep. Of 34 cold-sensitive neurons, 25 (74%) discharged more slowly during NREM sleep compared with waking (NREM/wake, < or = 0.8). This subpopulation of cold-sensitive neurons exhibited decreased thermosensitivity during NREM sleep. These results are consistent with a hypothesis that the activation of sleep-related warm-sensitive neurons and the deactivation of wake-related cold-sensitive neurons may play a key role in the onset and regulation of NREM sleep.

Animals↗
PubMed1995

Preoptic/anterior hypothalamic neurons: thermosensitivity in rapid eye movement sleep.

The thermosensitivity of 15 warm-sensitive neurons (WSNs) and 19 cold-sensitive neurons (CSNs) from the medial preoptic/anterior hypothalamus (POAH) was tested during wakefulness, non-rapid eye movement (NREM) sleep and rapid eye movement (REM) sleep by local POAH warming and cooling in freely moving cats. Thermosensitivity was quantified by three criteria, Q10, impulses per second per degree Celsius, and percent change per degree Celsius. Irrespective of the criterion used, WSNs did not exhibit a significant change in thermosensitivity during REM sleep compared with wakefulness and NREM sleep. In contrast, CSNs exhibited decreased mean thermosensitivity during REM sleep compared with wakefulness. CSNs as a group did not retain significant thermosensitivity in REM sleep. These findings are consistent with evidence that thermoeffector responses to cooling are lost in REM sleep, whereas some responses to warming are preserved.

Animals↗
PubMed1995

A thermoregulatory model of sleep control.

We hypothesize that non-rapid-eye-movement sleep (NREM) is controlled by thermoregulatory mechanisms of the preoptic/anterior hypothalamus. Circadian and homeostatic thermoregulatory processes may be integrated in this brain area. To investigate this hypothesis, we have developed a mathematical model of qualitative features of human sleep-waking behavior based on a thermoregulatory feedback control mechanism, with modulation by two circadian oscillators, one a temperature rhythm, the other modulating sleepiness. Homeostatic features of the sleep rhythm are generated by integration of a heat load associated with waking. Simulations under entrained conditions show that the model closely mimics typical features of human sleep rhythms, including a biphasic daily pattern of sleepiness and sleep-onsets and awakenings fixed in a descending phase and an ascending phase of the temperature rhythm, respectively. Sleep duration is strongly controlled by the phase difference between the two oscillators with the same period; these could represent two phase-differentiated expressions of a single oscillator. In addition, the simulation of sleep deprivation provides a natural interpretation of the experimentally observed phenomena, which shows that the homeostatic and the oscillatory aspects of the human circadian system is successfully integrated in our model. The promising results obtained suggest that the control of sleep-wake rhythm could be understood within the framework of the thermoregulation.

Body Temperature Regulation↗
PubMed1995

Dynamical features of thermoregulatory model of sleep control.

We have developed a quantitative model of human sleep-wake rhythms based on a thermoregulatory feedback control mechanism modulated by two circadian oscillators. Homeostatic features of sleep regulation are realized through the heat memory which represents the history of the masking process associated with sleep-wake cycles: heat load during wake and heat loss during sleep. Simulations under entrained conditions showed that the model closely mimics well-known features of human sleep-wake rhythm, and that the homeostatic and the oscillatory aspects of the human circadian system are successfully integrated in our model. In this paper, parameter dependency of the model behavior is studied by simulations. Because of its physiology-based structure, the parameter dependency could show the possible underlying mechanism for the typical features of human sleep-wake rhythm. In addition, the model stability is analyzed by the linear system theory and the simulations, which establishes the stability condition and suggests that the presented simulation results are basically stable. These results are informative to apply our model to actual data of sleep-wake rhythms, and to interpret them from the physiological point of view.

Body Temperature Regulation↗
PubMed1994

Regulation of posterior lateral hypothalamic arousal related neuronal discharge by preoptic anterior hypothalamic warming.

The posterior lateral hypothalamus (PLH) is a brain region involved in cortical activation and maintenance of behavioral arousal. Spontaneous and evoked neuronal activities were recorded in the PLH of cats before and during local warming of the preoptic-anterior hypothalamus (POAH). Forty-six percent of PLH neurons recorded in awake cats decreased spontaneous discharge during POAH warming. In the absence of POAH warming, these same cells exhibited significantly lower discharge rates in non-rapid eye movement (NREM) sleep compared to waking. Responses of PLH neurons to POAH warming were also investigated in sleeping cats to determine whether hypothalamic thermosensitive neurons modulated sleep-wake regulation across arousal states. POAH warming had no influence on spontaneous activities of PLH neurons during NREM sleep, but suppressed activity of a small subset of neurons during rapid eye movement (REM) sleep. Thus, during wakefulness or REM sleep, hypothalamic thermosensitive neurons may modulate behavioral state via inhibition or disfacilitation of arousal systems.

Animals↗
PubMed1994

Preoptic/anterior hypothalamic warming increases EEG delta frequency activity within non-rapid eye movement sleep.

The effects of mild POAH warming and cooling on EEG frequency patterns within sustained periods of NREM sleep were examined. EEG spectral power analysis showed that POAH warming increased delta (0.5-4.0 Hz) activity, but had no effect on theta or sigma frequencies. Delta power was also increased during a 1 h recovery period, following warming. POAH cooling had no EEG effects. Since delta power is thought to be an index of sleep depth, our findings suggest that POAH thermoregulatory mechanisms participate in the regulation of the depth of NREM sleep.

Animals↗
PubMed1994

REM sleep-suppressing effects of atropine in cats vary with environmental temperature.

Because the occurrence of rapid eye movement (REM) sleep is critically dependent upon an animal's thermal balance, acute pharmacological treatments may effect REM sleep through effects on thermoregulation. We describe how manipulating ambient temperature (T(a)) alters the REM sleep-suppressing effects of systemically-administered atropine, a muscarinic receptor antagonist, in adult cats. At a T(a) of 23 degrees C , atropine (0.5 mg/kg) produced a significant reduction in REM sleep time that persisted for about 8 h of a 16 h recording period. Hypothalamic temperature fell below control levels for about 4 h following atropine. At a T(a) of 30 degrees C, the same dose of atropinehad no significant effect on REM sleep time, or hypothalamic temperature. These findings indicate the importance of considering the possible role of thermoregulation in drug-induced effects on REM sleep.

Acetylcholine↗
PubMed1993

Sleep-wake disturbances in an animal model of chronic cholinergic insufficiency.

Rats reared on a diet in which choline is replaced with N-aminodeanol (NADE), undergo > 50% replacement of brain acetylcholine with acetylated NADE, a false cholinergic transmitter. We examined amounts of sleep and wakefulness in 7 littermate pairs of rats fed either NADE-substituted, or a choline control diet for > 100 days after weaning. During the lights-on portion of the 12/12 h light/dark cycle, NADE rats spent more time awake, and less time in both non-REM and REM sleep compared to littermate controls. Average durations of waking episodes were significantly increased in NADE rats. During the 12 h dark period, there were no between-group differences in sleep-waking amounts. Behavioral hyper-responsiveness which interferes with sleep onset, combined with reduced activity in brainstem cholinergic mechanisms involved in REM sleep generation may underlie daytime sleep-waking disturbances in NADE rats.

Acetylation↗
PubMed1991

Exposure to heat restores sleep in cats with preoptic/anterior hypothalamic cell loss.

Evidence suggests that thermosensitive neurons of the preoptic/anterior hypothalamus (POAH) influence sleep- and arousal-regulating mechanisms. We examined the effects of POAH cell loss, produced by microinjection of neurotoxin (N-methyl-DL-aspartic acid), on sleep and thermoregulation in cats. Cats with bilateral POAH cell loss did not defend their body temperatures in the heat as effectively as normals, and did not initiate panting until brain temperatures rose to abnormally high levels. During 14 h polygraphic recordings of sleep-waking state conducted at an ambient temperature (Ta) of 23 degrees C, POAH-damaged cats exhibited reduced sleep. Amounts of deep slow-wave sleep (SWS2) were significantly less than prelesion values through 7 weeks postlesion; significant REM sleep deficits persisted for 5 weeks. However, these sleep disturbances were dramatically attenuated when cats were exposed to high Tas. During 6 h recordings at Tas of 13, 23, or 33 degrees C, total sleep time was greatest at 33 degrees C at both 2 and 4 weeks postlesion. At 4 weeks, amounts of SWS2 at 33 degrees C were similar to maximal prelesion values. Increased sleep at 33 degrees C was associated with elevated brain temperatures. The finding that, after POAH damage, abnormally high brain temperatures were required to elicit both panting and normal amounts of SWS suggests that impaired hypothalamic sensitivity to heat was responsible for both deficits. These results support the hypothesis that thermosensitive neurons participate in the tonic regulation of sleep and arousal.

Animals↗
PubMed1990

Keeping cool: a hypothesis about the mechanisms and functions of slow-wave sleep.

Current evidence supports a hypothesis that slow-wave sleep (SWS) in mammals and birds is controlled by thermoregulatory mechanisms, and provides brain and body cooling as a primary homeostatic feedback process. Recent work has identified a medial preoptic area anterior hypothalamic and basal forebrain neuronal network which integrates thermoregulatory and hypnogenic controls. This network induces EEG and behavioral deactivation, in part, through suppression of the reticular activating system. Studies have shown that SWS, like other heat loss processes, is facilitated when brain temperature exceeds a threshold level. This threshold is hypothesized to be determined by responses of POAH thermosensitive neurons and to be regulated by both circadian and homeostatic processes. Many known chemomodulators of SWS appear to act on this hypnogenic thermoregulatory system. At a functional level, SWS-induced brain and body cooling would provide several adaptations including lower energy utilization, reduced cerebral metabolism, protection of the brain against the sustained high temperatures of wakefulness, facilitation of immune defense processes and regulation of the timing of behavioral activity relative to the circadian light-dark cycle. This concept provides a comprehensive model for analysis of sleep homeostasis.

Animals↗
PubMed1990

Effects of systemic atropine sulfate administration on the frequency content of the cat sensorimotor EEG during sleep and waking.

Sensorimotor electroencephalogram (EEG) frequencies in cats were evaluated with power spectral analysis before and after 3 doses of atropine sulfate. All doses of atropine tested caused enhanced EEG slow waves (0-7 Hz) and spindles (8-15 Hz) during waking immobility, and postdrug frequency profiles during slow-wave sleep and waking immobility were identical. With 0.75 mg/kg atropine, movement (head movement, locomotion) resulted in EEG desynchronization and reduced power in all frequencies less than 24 Hz. After 1.5 or 3.0 mg/kg atropine, power in low frequencies remained elevated during movement, but power in spindle frequencies was significantly reduced compared with other states. During active REM sleep after 1.5 mg/kg atropine, power in spindle frequencies was significantly lower than that during quiet REM sleep. These results indicate that the sensorimotor cortical EEG in cats is under the control of multiple systems. At least 1 of these systems is active during movement, and its actions are resistant to muscarinic receptor blockade.

Animals↗