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D McGinty

Publications and source records attributed to D McGinty.

At least 19 recordsLinked to original sources
PubMed2005

Different neuronal populations of the rat median preoptic nucleus express c-fos during sleep and in response to hypertonic saline or angiotensin-II.

The median preoptic nucleus (MnPN) of the hypothalamus contains sleep-active neurones, and sleep-related Fos-immunoreactivity (IR) in this nucleus is primarily expressed in GABAergic cells. The MnPN also contains cells responsive to hypertonic saline and to angiotensin-II (Ang-II). To clarify functional relationships between MnPN neurones involved in the regulation of sleep and body fluid homeostasis, we examined c-fos expression in the MnPN after administration of hypertonic saline and Ang-II in both spontaneously sleeping and sleep-deprived rats. Systemic administration of hypertonic saline and intracerebroventricular (i.c.v.) injection of Ang-II increased Fos-IR in both spontaneously sleeping and sleep-deprived rats, compared to control animals. To determine if the population of MnPN neurones activated in response to osmotic and hormonal stimuli is similar to or different from neurones activated during sleep, we quantified Fos-IR in MnPN GABAergic neurones in spontaneously sleeping hypertonic saline- and Ang-II-treated rats versus respective control rats. Fos-IR evoked by these treatments occurred primarily (80-85%) in non-GABAergic neurones. Findings of the present study provide evidence that separate populations of MnPN neurones are involved in the regulation of sleep and body fluid homeostasis.

Angiotensin II↗
PubMed2005

Persistence of sleep-temperature coupling after suprachiasmatic nuclei lesions in rats.

The suprachiasmatic nucleus (SCN) regulates the circadian rhythms of body temperature (T(b)) and vigilance states in mammals. We studied rats in which circadian rhythmicity was abolished after SCN lesions (SCNx rats) to investigate the association between the ultradian rhythms of sleep-wake states and brain temperature (T(br)), which are exposed after lesions. Ultradian rhythms of T(br) (mean period: 3.6 h) and sleep were closely associated in SCNx rats. Within each ultradian cycle, nonrapid eye movement (NREM) sleep was initiated 5 +/- 1 min after T(br) peaks, after which temperature continued a slow decline (0.02 +/- 0.006 degrees C/min) until it reached a minimum. Sleep and slow wave activity (SWA), an index of sleep intensity, were associated with declining temperature. Cross-correlation analysis revealed that the rhythm of T(br) preceded that of SWA by 2-10 min. We also investigated the thermoregulatory and sleep-wake responses of SCNx rats and controls to mild ambient cooling (18 degrees C) and warming (30 degrees C) over 24-h periods. SCNx rats and controls responded similarly to changes in ambient temperature. Cooling decreased REM sleep and increased wake. Warming increased T(br), blunted the amplitude of ultradian T(br) rhythms, and increased the number of transitions into NREM sleep. SCNx rats and controls had similar percentages of NREM sleep, REM sleep, and wake, as well as the same average T(b) within each 24-h period. Our results suggest that, in rats, the SCN modulates the timing but not the amount of sleep or the homeostatic control of sleep-wake states or T(b) during deviations in ambient temperature.

Animals↗
PubMed2004

Interleukin 1beta enhances non-rapid eye movement sleep and increases c-Fos protein expression in the median preoptic nucleus of the hypothalamus.

Interleukin 1beta (IL-1) is a key mediator of the acute phase response in an infected host and acts centrally to coordinate responses to an immune challenge, such as fever and increased non-rapid eye movement (NREM) sleep. The preoptic area (POA) is a primary sleep regulatory center in the brain: the ventrolateral POA (VLPO) and median preoptic nucleus (MnPN) each contain high numbers of c-Fos protein immunoreactive (IR) neurons after sleep but not after waking. We hypothesized that IL-1 mediates increased NREM sleep through activation of these sleep-active sites. Rats injected intracerebroventricularly with IL-1 (10 ng) at dark onset spent significantly more time in NREM sleep 4-5 h after injection. This increase in NREM sleep was associated with increased numbers of Fos-IR neurons in the MnPN, but not in the VLPO. Fos IR in the rostral MnPN was significantly increased 2 h post IL-1 injection, although the percentage of NREM sleep in the preceding 2 h was the same as controls. Fos IR was also increased in the extended VLPO 2 h postinjection. Finally, Fos IR in the MnPN did not differ significantly between IL-1 and vehicle-treated rats that had been sleep deprived for 2 h postinjection, but it was increased in VLPO core. Taken together, these results suggest that Fos IR in the MnPN after IL-1 is not independent of behavioral state and may require some threshold amount of sleep for its expression. Our results support a hypothesis that IL-1 enhances NREM sleep, in part, through activation of neurons in the MnPN of the hypothalamus.

Animals↗
PubMed2004

Sleep-promoting functions of the hypothalamic median preoptic nucleus: inhibition of arousal systems.

Recent work supports the hypotheses developed by von Economo and Nauta and elaborated by Sallanon et al. that the POA contains a sleep-promoting output that opposes wake-promoting neuronal groups in the PH. The POA gives rise to descending pathways that terminate within wake-promoting populations in pLH, PH and midbrain. Current evidence suggests that this output originates in POA sleep-active GABAergic neurons. This output also seems to convey the signals of homeostatic drive. Disynaptic projections from the SCN to both MnPN and VLPO were recently identified. These may regulate the circadian control of sleep propensity. The hypothesis that the descending projections from POA sleep-active neurons to sites of arousal-related neurons originates in GABAergic neurons must be confirmed. Also to be further clarified is the anatomical distribution of putative sleep-active GABAergic neurons within the POA. Segregated groups have been found in the MnPN and VLPO, but unit recording studies of sleep-active neurons, lesion studies and local neurochemical application studies all indicate that sleep-active neurons may be found diffusely in the POA and adjacent areas. The MnPN has been shown previously to be involved in water balance and blood pressure regulation and to be responsive to hyperthermia. Our studies suggest that this nucleus also contains sleep-active, putative sleep-promoting neurons. However, interactions between sleep control and physiological variables must be considered. In particular, the details of neuronal basis of the coupling of warm-sensitive neurons in MnPN to the POA hypnogenic output has not been explored. It is also worth noting that both the VLPO and MnPN lie close to the ventricular and subarachnoid surface and are punctuated by radial arterioles. The possibility that the sleep-regulatory functions of these sites is coupled to physiological signals conveyed through epithelial cells has been suggested for the actions of PGD2 but has yet to be explored in detail for other putative hypnogens.

Action Potentials↗
PubMed2001

Subregional organization of preoptic area/anterior hypothalamic projections to arousal-related monoaminergic cell groups.

Pathways mediating the generation and/or maintenance of sleep reside within the preoptic/anterior hypothalamus (POAH). Reproduction, water balance, thermoregulation, and neuroendocrine functions are also associated with POAH, but it is not fully understood whether sleep is consolidated with these behavioral and physiological functions, or whether sleep-related circuitry is segregated from other POAH regions. Recent studies indicate that sleep mechanisms may be localized to the ventrolateral preoptic area (VLPO) and that this region sends inhibitory projections to waking/arousal-related neurons in the histaminergic tuberomammillary nucleus (TM), the noradrenergic locus coeruleus (LC), and the serotonergic dorsal raphe (DR). The present study is a quantitative investigation of preoptic area efferents to these monoaminergic groups. The results demonstrate that biotinylated dextran injections in the VLPO region reveal a robust innervation of TM that was as much as five times greater than innervation derived from other POAH subregions. The innervation of TM originated almost exclusively from injection sites in the region of galanin neurons. VLPO projections to the LC were moderately dense and were greater than in other POAH regions except for equivalent input from the medial preoptic area. Projections to the dorsal raphe were equivalent to LC innervation and were generally two to three times greater from VLPO than from other POAH regions, except for projections from the lateral preoptic region, which were similar in magnitude. The rostral and caudal levels projected more to the TM, whereas the midrostral region of VLPO strongly innervated the LC core. These findings, with recent studies demonstrating medial and lateral extensions of the sleep-related VLPO neuronal group, indicate that descending arousal state control may be mediated by this specific galaninergic/gamma-aminobutyric acid (GABA)ergic cell group.

Animals↗
PubMed2001

Subcutaneous administration of nicotine changes dorsal raphe serotonergic neurons discharge rate during REM sleep.

In the present study nicotine (0.1 mg/kg, s.c.) increased discharge rate of putative dorsal raphe (DRN) serotonergic neurons of behaving rats during REM sleep (362.61%), without any significant change during waking and non-REM sleep. Since serotonergic DRN neurons gate PGO onset, these results suggest that nicotine-induced suppression of PGO spikes during REM sleep previously reported is achieved through stimulation of dorsal raphe serotonergic cells.

Action Potentials↗
PubMed2001

Preoptic area sleep-regulating mechanisms.

Evidence is summarized for the existence of a sleep-regulating mechanism within the preoptic area of the hypothalamus, including the results of lesion, stimulation, and neuronal recording studies. Recent findings employing the c-fos protein immunohistochemical method, have localized putative sleep-regulatory neurons to the ventrolateral preoptic area (vlPOA) and the median preoptic nucleus (MnPn). Electrophysiological studies have confirmed the presence of neurons with sleep-related discharge in the vlPOA. Neurons in the vlPOA that exhibit c-fos protein immunoreactivity during sleep contain the inhibitory neuromodulators galanin and gamma-aminobutyric acid (GABA). These neurons also project to monoaminergic arousal systems, particularly the histaminergic cell groups in the posterior hypothalamus. POA neurons can be hypothesized to provide sleep-related inhibitory control over multiple arousal systems in the forebrain and brainstem.

Action Potentials↗
PubMed2000

Effects of lateral preoptic area application of orexin-A on sleep-wakefulness.

Deficiency of orexin, a newly discovered hypothalamic peptide, is thought to lead to abnormal sleepiness and cataplexy in both human narcolepsy and animal models of the disease. As the POA contains extensive orexin terminals and is established as a sleep/arousal regulatory site, we evaluated a hypothesis that this site is a target for the arousal-inducing effects of orexin. Orexin-A was microinjected into lateral preoptic area (IPOA) and the effects on sleep-wakefulness and brain temperature were studied. Compared to saline vehicle control, orexin-A induced an increase in wakefulness for 70 min and suppressed all sleep stages, especially SWS2 and REM for 80 and 90 min, respectively. Brain temperature was not differentially affected by orexin-A compared to saline control. The orexin-induced arousal and REM suppression are consistent with the orexin-deficiency model of narcolepsy. Our results suggest that the IPOA orexin terminal field or adjacent structures may be a locus of arousal regulation by this peptide and a substrate of sleep-wake regulatory deficits in narcolepsy.

Animals↗
PubMed2000

Discharge modulation of rat dorsal raphe neurons during sleep and waking: effects of preoptic/basal forebrain warming.

In cats, putative serotonergic neurons (PSNs) recorded from the dorsal raphe nucleus (DRN) across the sleep-wake cycle exhibit the so-called rapid eye movement sleep-off (REM-off) discharge pattern. Since, the sleep-wake discharge patterns of DRN neurons in behaving rats is poorly known, the present study examined this neuronal populations. The PSNs recorded in this study exhibited: (1) progressive decrease in discharge rate from waking to NREM to REM sleep; (2) long action potential duration, and (3) reduction of discharge rate after systemic administration of a selective 5-HT(1A) agonist, (+/-)-8-hydroxy-2-(di-n-propylamino) tetralin hydrobromide (8-OH-DPAT). Evidence supports the hypothesis that NREM sleep is modulated by thermoregulatory mechanisms localized in the preoptic area and adjacent basal forebrain (POA/BF). We previously reported that POA/BF warming suppresses the discharge of wake-promoting neurons in the posterior hypothalamus and the basal forebrain. Since the DRN is one component of the brainstem arousal system and receives projections from POA/BF, we examined the effects of local POA/BF warming by 1.5-2.0 degrees C during waking on the discharge of DRN neurons. POA/BF warming reduced the discharge in 14 of 19 PSNs and in 12 of 17 other wake-related neurons in the DRN. DRN neuronal discharge reduction occurred without accompanying EEG frequency or behavioral changes. These results suggest that PSNs recorded in DRN in unrestrained and unanesthetized rats exhibit a "wake-active REM-off" discharge pattern and further support the hypothesis that the POA/BF warm-sensitive hypnogenic system induces sleep by a coordinated inhibition of multiple arousal systems including that modulated by the DRN.

8-Hydroxy-2-(di-n-propylamino)tetralin↗
PubMed2000

Discharge patterns of neurons in cholinergic regions of the basal forebrain during waking and sleep.

A subset of neurons recorded in the magnocellular basal forebrain (mBF) of cats and rats exhibit elevated discharge rates during waking and REM sleep, and diminished discharge during sleep with cortical EEG synchrony (nonREM sleep). This pattern is observed in mBF neurons in cats with identified ascending projections, and in neurons located in cholinergic regions of the rat mBF. However, the cholinergic versus noncholinergic nature of recorded cells could not be determined with the extracellular recording method employed. During waking, discharge of mBF neurons is strongly movement-related. Peak discharge rates occur during a variety of head and limb movements. Discharge rates during waking immobility are reduced by >50% compared to rates during waking movement. The absence of movement accounts for more of the variance in discharge across the sleep-wake cycle than does the presence of cortical EEG synchronization. Several factors participate in the regulation of mBF neuronal activity across arousal states. Tonic inhibition mediated by adenosine appears to be present during both waking and sleep. In some mBF neurons, increased GABAergic inhibition contributes to nonREM sleep-related reductions in discharge rate. Fluctuations in mBF cell activity during waking behaviors may reflect changing excitatory input from neurons in the pontine and midbrain tegmentum.

Animals↗
PubMed2000

Sleep-related c-Fos protein expression in the preoptic hypothalamus: effects of ambient warming.

Preoptic area (POA) neuronal activity promotes sleep, but the localization of critical sleep-active neurons is not completely known. Thermal stimulation of the POA also facilitates sleep. This study used the c-Fos protein immunostaining method to localize POA sleep-active neurons at control (22 degrees C) and mildly elevated (31.5 degrees C) ambient temperatures. At 22 degrees C, after sleep, but not after waking, we found increased numbers of c-Fos immunoreactive neurons (IRNs) in both rostral and caudal parts of the median preoptic nucleus (MnPN) and in the ventrolateral preoptic area (VLPO). In animals sleeping at 31.5 degrees C, significantly more Fos IRNs were found in the rostral MnPN compared with animals sleeping at 22 degrees C. In VLPO, Fos IRN counts were no longer increased over waking levels after sleep at the elevated ambient temperature. Sleep-associated Fos IRNs were also found diffusely in the POA, but counts were lower than those made after waking. This study supports a hypothesis that the MnPN, as well as the VLPO, is part of the POA sleep-facilitating system and that the rostral MnPN may facilitate sleep, particularly at elevated ambient temperatures.

Animals↗
PubMed1999

Adenosinergic modulation of rat basal forebrain neurons during sleep and waking: neuronal recording with microdialysis.

1. The cholinergic system of the basal forebrain (BF) is hypothesized to play an important role in behavioural and electrocortical arousal. Adenosine has been proposed as a sleep-promoting substance that induces sleep by inhibiting cholinergic neurons of the BF and brainstem. However, adenosinergic influences on the activity of BF neurons in naturally awake and sleeping animals have not been demonstrated. 2. We recorded the sleep-wake discharge profile of BF neurons and simultaneously assessed adenosinergic influences on wake- and sleep-related activity of these neurons by delivering adenosinergic agents adjacent to the recorded neurons with a microdialysis probe. Discharge rates of BF neurons were recorded through two to three sleep-wake episodes during baseline (artificial cerebrospinal fluid perfusion), and after delivering an adenosine transport inhibitor (s-(p-nitrobenzyl)-6-thioinosine; NBTI), or exogenous adenosine, or a selective adenosine A1 receptor antagonist (8-cyclopentyl-1, 3-dimethylxanthine; CPDX). 3. NBTI and adenosine decreased the discharge rate of BF neurons during both waking and non-rapid eye movement (NREM) sleep. In contrast, CPDX increased the discharge rate of BF neurons during both waking and NREM sleep. These results suggest that in naturally awake and sleeping animals, adenosine exerts tonic inhibitory influences on BF neurons, supporting the hypothesized role of adenosine in sleep regulation. 4. However, in the presence of exogenous adenosine, NBTI or CPDX, BF neurons retained their wake- and sleep-related discharge patterns, i.e. still exhibited changes in discharge rate during transitions between waking and NREM sleep. This suggests that other neurotransmitters/neuromodulators also contribute to the sleep-wake discharge modulation of BF neurons.

Adenosine↗
PubMed1999

GABAA receptor modulation of temperature sensitive neurons in the diagonal band of Broca in vitro.

Several regions of the brain, including the horizontal limb of the diagonal band of Broca (HDB), contain neurons that are responsive to changes in local temperature. These neurons are hypothesized to participate in thermoregulation and sleep-wake control. The HDB contains a large number of gamma-aminobutyric acid (GABA) terminals, and it has many neurons that utilize GABA as a neurotransmitter. Therefore, in this study we characterized the in vitro effects of the GABAA receptor agonist muscimol (0.5, 0.25, 0.1 and 0.0625 microM doses) and the GABAA receptor antagonist bicuculline (3.0 and 1.0 microM doses) on the firing rate and thermosensitivity of HDB neurons. Of the 51 neurons recorded in a submerged slice chamber, 53% were warm sensitive, 45% were temperature insensitive and 2% were cold sensitive. All neurons exposed to bath applied muscimol exhibited reductions in both firing rate and thermosensitivity. Muscimol induced reductions were maintained for at least 20 min after washout. Neurons exposed to bicuculline had no change in firing rate or thermosensitivity. However, after bicuculline washout there were reductions in both firing rate and thermosensitivity. These findings support the hypothesis that GABAA receptor induced inhibition of HDB thermosensitive neurons can modulate both thermoregulation and sleep-wake control.

Animals↗
PubMed1999

Sleep-waking discharge of neurons in the posterior lateral hypothalamus of the albino rat.

The sleep-waking discharge patterns of neurons in the posterior lateral hypothalamus (PLH) were investigated in the rat. Previous studies in the cat demonstrated that this region contained neurons that fired tonically at low rates (2-4 Hz) during waking, decreased firing in non-rapid eye-movement (NREM) sleep and nearly ceased firing during rapid eye-movement (REM) sleep. These "REM-off" neurons were proposed to be histaminergic neurons of the tuberomammillary nucleus (TM). Since many anatomical and physiological studies are performed in the rat, we sought to examine the sleep-waking discharge of these neurons in this animal. We found three main types of discharge patterns among PLH neurons. Waking-related neurons decreased their discharge in NREM sleep, and remained at low rates during REM sleep. A subpopulation of these neurons discharged very little during REM sleep (<0.2 Hz) (REM-off neurons). Waking/REM-related neurons decreased their discharge in NREM sleep and returned to waking rates in REM sleep. REM-related neurons decreased their discharge in NREM sleep and increased their discharge during REM sleep higher than waking rates. No NREM-related discharge patterns were recorded. Waking-related and waking/REM-related neurons were similar in location within the PLH and action potential duration. Some REM-off and other waking-related neurons were recorded within the boundaries of the histaminergic TM, however, not all waking-related and REM-off neurons were found within this region. Furthermore, neurons with waking/REM-related and state-indifferent discharge patterns were localized within the TM. These results suggest that waking-related and/or REM-off neurons may not be exclusively histaminergic in rats.

Animals↗
PubMed1999

A model-based interpretation of the biphasic daily pattern of sleepiness.

We developed a thermoregulatory model of sleep control based on the hypothesis that non-rapid eye-movement sleep participates in homeostatic thermoregulation. This model successfully reproduced several qualitative features of human sleep/wake cycles during entrained as well as the internally desynchronized states. Among the reproduced features, generation mechanisms of the biphasic sleepiness distribution are studied here in the light of the model structure. Harmonic analysis is employed for this purpose. Through linearizations and confining the harmonics of the masking process to the fundamental component, a simplified representation of sleepiness is obtained. The simplified sleepiness is constructed with the fundamental circadian, the second harmonic components, and the constant (DC). The bimodality of the sleepiness is shown to be made by the second harmonic which is added to the fundamental component. The behavior of their amplitudes and phase positions are investigated under the varied sleep/wake durations and phase differences between the oscillators. Since the sleepiness generated by our model is roughly mimicked by the simplified representation under diverse conditions, this simplification can be regarded as adequate. From the behavior of the constituents of respective harmonic components, the fundamental component is shown to originate from the sleep/wake masking process and the circadian oscillators; the second harmonic from the multiplicative interactions between the circadian oscillators and the sleep/wake masking process. These results indicate that the rhythmic processes are principal constituents of the sleepiness, at least in the steady state.

Body Temperature Regulation↗
PubMed1999

Thermoregulatory model of sleep control: losing the heat memory.

Thermoregulatory mechanisms were hypothesized to provide primary control of non-rapid-eye-movement sleep (NREM). On the basis of this hypothesis, we incorporated the thermoregulatory feedback loops mediated by the "heat memory," heat load, and loss processes associated with sleep-wake cycles, which were modulated by two circadian oscillators. In addition, hypnogenic warm-sensitive neurons (HWSNs) were assumed to integrate thermoregulation and NREM control. The heat memory described above could be mediated by some sleep-promoting substances. In this paper, considering the possible carrier of the heat memory, its losing process is newly included in the model. The newly developed model can generate the appropriate features of human sleep-wake patterns. One of the special features of the model is to generate the bimodal distribution of the sleepiness. This bimodality becomes distinct, as the losing rate of the heat memory decreases or the amplitude of the Y oscillator increases. The theoretical analysis shows the losing rate of the heat memory control's rapidity of model response to a thermal perturbation, which is confirmed by simulating the responses with various losing rates to transient heat loads ("heat load pulse"). The sleepiness exhibits large responses to the heat load pulses applied in the early and late phases of wake period, while the response is significantly reduced to the pulse applied in the supposed wake-maintenance zone. This bimodality of the response appears to reflect the sensitivity of the HWSNs. In addition, the early pulse raises the immediate sleepiness rather than the nocturnal sleepiness, while the heat load pulse applied in the later phase of waking period significantly raises the sleepiness during a nocturnal sleep. In simulations of sleep deprivation, the discontinuous relationship between recovery sleep length and deprivation time is reproduced, where the critical sleep deprivation time at which the recovery sleep length jumps is extended as the losing rate increases. This is possibly due to the dissipation of the heat memory accumulated by the sleep deprivation. The simulation results here qualitatively reproduce the experimental observations or predict the intriguing phenomena of human circadian rhythms. Therefore, our model could provide a novel framework for investigating the relationship between thermoregulation and sleep control processes.

Algorithms↗