Biomedical subjects

R Lydic

Publications and source records attributed to R Lydic.

At least 55 records · Page 3Linked to original sources

PubMed1990

Parabrachial neuron discharge in the cat is altered during the carbachol-induced REM sleep-like state (DCarb).

Pontine parabrachial neurons have been suggested to play a regulatory role in both respiratory and sleep cycle control. Encouraged by the finding that microinjections of the cholinergic agonist carbachol into the medial pontine reticular formation (mPRF) of the cat produced respiratory changes paralleling those observed during rapid eye movement (REM) sleep (Neurosci. Lett., 102 (1989) 211-216), this study tested the hypothesis that cholinergic mechanisms in the mPRF can also cause state-dependent changes in the discharge of parabrachial neurons. This paper describes extracellular recordings of parabrachial neurons during REM sleep and during the carbachol-induced REM sleep-like state (DCarb). Cells which were activated (REM-on) or inactivated (REM-off) during REM maintained the same state-dependent firing patterns during the DCarb state. These results support the hypothesis that cholinergic mechanisms in the mPRF can cause state-dependent changes in the discharge of parabrachial neurons.

Animals↗

PubMed1989

Cholinoceptive pontine reticular mechanisms cause state-dependent respiratory changes in the cat.

This study tested the hypothesis that cholinoceptive regions of the medial pontine reticular formation (mPRF), long known to play a role in regulating the sleep cycle, can also causally alter the respiratory cycle. In 4 cats, sleep and wakefulness were polygraphically recorded while simultaneous measures were taken of rate of breathing, tidal volume, minute ventilation, respiratory cycle timing, and end-tidal CO2 concentration. Respiration during naturally occurring rapid eye movement (REM) sleep was compared to breathing during wakefulness and during the REM sleep-like state (D Carb) caused by mPRF microinjections of the cholinergic agonist carbachol. The results demonstrate for the first time that non-respiratory regions of the cholinoceptive mPRF can cause statistically significant state-dependent alterations in respiration.

Animals↗

PubMed1989

The carbachol-induced enhancement of desynchronized sleep signs is dose dependent and antagonized by centrally administered atropine.

Considerable data show that microinjection of carbachol into the pontine reticular formation produces a desynchronized (D) sleep-like state. The present study examined the hypothesis that this carbachol-induced enhancement of D sleep signs is mediated by muscarinic, cholinergic receptors. This hypothesis was tested by quantifying the dose-dependent effects of centrally administered carbachol on the D sleep-like state and by pretreating the animals with centrally administered atropine. Six dosages of carbachol were microinjected into the pontine reticular formation of conscious cats and polygraphic measures of behavioral state were recorded. The percentage, latency, duration, frequency, and time course of the carbachol-induced D sleep-like state were dose dependent. Centrally administered atropine competitively antagonized the ability of carbachol to induce the D sleep-like state, whereas pontine administration of L-glutamate did not significantly alter D sleep. These data demonstrate that muscarinic, cholinergic receptors within the pontine reticular formation mediate the phenomenon of cholinoceptive D sleep sign enhancement.

Animals↗

PubMed1989

Central pattern-generating neurons and the search for general principles.

This paper selectively reviews cellular-level studies of neurons and neural networks that function to generate rhythmic physiological and behavioral events. Studies of biological rhythms during the last 75 years have modified Sherrington's concept of nervous tissue as primarily reflexive to include the fact that some neuronal activity is also endogenously rhythmic. As a functional group, neurons that initiate and maintain physiological or behavioral rhythms are referred to as central pattern generators. Comparative studies reveal a disorienting variety of biological rhythms and underlying central pattern generator control mechanisms. This paper outlines the taxonomic diversity of biological rhythms, the strengths and limitations of various models for studying central pattern generators, and the ongoing search for general principles of rhythm generation. Studies of rhythmic phenomena displayed by intact, unanesthetized mammals have been greatly enriched by data and concepts derived from invertebrate central pattern generators. This multidisciplinary influence is illustrated by reviewing recent work that aims to localize and characterize the cellular bases of circadian rhythms, reproductive rhythms, and rhythmic changes in motor control related to the sleep cycle. The paper concludes by describing studies that aim to derive a cellular-level account for oscillator interaction, sensory feedback, and the homeostatic modulation of biological rhythms.

Animals↗

PubMed1989

State-dependent hypotonia in posterior cricoarytenoid muscles of the larynx caused by cholinoceptive reticular mechanisms.

The neural control of the accessory respiratory muscles regulating upper airway patency is poorly understood. This is particularly true with regard to the declines in electromyographic (EMG) activity of upper airway muscles during sleep. To specify the cellular mechanisms causing decreased upper airway muscle tone during sleep, we used an established pharmacological model of rapid eye movement (REM) sleep. With this model, a REM sleep-like state was reliably produced by microinjecting the cholinergic agonist carbachol directly into the pontine reticular formation of the cat. EMG recording were taken from the posterior cricoarytenoid (PCA) muscles of the larynx during wakefulness and the carbachol-induced, REM sleep-like state. This experimental model had not been previously used to study the neuropharmacological control of the upper airway. The results revealed a dose-dependent decrease in PCA muscle tone caused by pontine microinjections of carbachol. To investigate the cholinergic specificity of these effects, the muscarinic cholinergic antagonist pirenzepine was centrally administered before carbachol. Pirenzepine pretreatment effectively blocked the carbachol-induced, REM sleep-like state and attendant changes in muscle tone. These results specify for the first time that muscarinic cholinergic mechanisms within the pontine reticular formation can causally mediate state-dependent hypotonia in accessory respiratory muscles of the upper airway.

Animals↗

PubMed1987

Increased ponto-geniculo-occipital (PGO) wave frequency following central administration of neostigmine.

In all mammals so far investigated the occurrence of ponto-geniculo-occipital (PGO) waves precedes the onset and maintenance of desynchronized (D) sleep. As unitary electrographic events, PGO waves provide an index for quantitative evaluation of physiological D sleep or the D sleep-like state evoked by centrally administered acetylcholinesterase inhibitors. The present study characterized PGO wave frequency and time course following central administration of neostigmine bromide (Neo). The results show that Neo produced a dose-dependent increase in PGO wave frequency and time course when injected into brainstem regions other than areas containing putative PGO wave generating neurons. These results support the concept that PGO waves and D sleep are generated by an anatomically distributed network of cholinoceptive neurons.

Animals↗

PubMed1987

In vivo metabolic activity of the suprachiasmatic nuclei: non-uniform intranuclear distribution of 14C-labeled deoxyglucose uptake.

Anatomical techniques have shown that the suprachiasmatic nuclei (SCN) are organized into distinct dorsomedial and ventrolateral subdivisions. As a functional correlate to this morphological organization, the intranuclear distribution of SCN glucose utilization was mapped using the autoradiographic 14C-labeled deoxyglucose method. In nocturnal rats and diurnal squirrel monkeys injected with the tracer during the light portion of the light-dark cycle, the middle of the SCN was metabolically more active than its rostral or caudal ends. No obvious dorsomedial/ventrolateral parcellation of SCN functional activity was disclosed. The rostrocaudal metabolic contour persisted unchanged in the absence of external light and resembled the 3-dimensional shape of the SCN (the highest metabolic activity was generally found at the largest cross-sectional area). This result is discussed with respect to its implications for the generation of circadian rhythmicity by the endogenous pacemaker in the SCN.

Animals↗

PubMed1987

Pontogeniculooccipital waves: spontaneous visual system activity during rapid eye movement sleep.

1. Pontogeniculooccipital (PGO) waves are recorded during rapid eye movement (REM) sleep from the pontine reticular formation, lateral geniculate bodies, and occipital cortex of many species. 2. PGO waves are associated with increased visual system excitability but arise spontaneously and not via stimulation of the primary visual afferents. Both auditory and somatosensory stimuli influence PGO wave activity. 3. Studies using a variety of techniques suggest that the pontine brain stem is the site of PGO wave generation. Immediately prior to the appearance of PGO waves, neurons located in the region of the brachium conjunctivum exhibit bursts of increased firing, while neurons in the dorsal raphe nuclei show a cessation of firing. 4. The administration of pharmacological agents antagonizing noradrenergic or serotonergic neurotransmission increases the occurrence of PGO waves independent of REM sleep. Cholinomimetic administration increases the occurrence of both PGO waves and other components of REM sleep. 5. Regarding function, the PGO wave-generating network has been postulated to inform the visual system about eye movements, to promote brain development, and to facilitate the response to novel environmental stimuli.

Animals↗

PubMed1987

State-dependent aspects of regulatory physiology.

This paper provides a brief and selective review of recent work concerning the alterations in thermoregulation, cardiovascular, and respiratory physiology that occur as a function of different states of sleep and wakefulness. These state-dependent changes in physiology were once regarded as a source of unwanted variance to be surgically or pharmacologically eliminated. The research paradigm championed by the work described here, however, requires that the endogenously generated state changes be recognized as potent independent variables influencing physiological control systems. Much evidence suggests that central monoamine-containing neurons mediate many of the state-dependent changes in thermoregulatory and cardiopulmonary physiology. A general conclusion emerging from these data is that studies of state-dependent physiology are not merely descriptive; they are essential for a complete characterization of the cellular and molecular mechanisms underlying regulatory physiology.

Activity Cycles↗

PubMed1987

Serotonin neurons and sleep. I. Long term recordings of dorsal raphe discharge frequency and PGO waves.

Brain stem transection studies suggest that pontine neurons play a key role in regulating the mammalian sleep cycle. The serotonin (5-HT) hypothesis originally postulated that pontine 5-HT containing neurons directly initiated and maintained synchronized or NREM sleep and "primed" rapid eye movement (REM) sleep. Contrary to the predictions of this hypothesis, single unit recordings from the serotonergic dorsal raphe nucleus (DRN) have uniformly shown that DRN discharge rate is positively correlated with behavioral arousal but negatively correlated with both the NREM and REM phases of sleep. These findings required revision of the original 5-HT hypothesis and suggested instead that DRN discharge may influence the maintenance of behavioral arousal and, by ceasing to discharge, may contribute to the generation of NREM and REM sleep. The purpose of this paper was to quantitatively assess the strength of the correlation between DRN discharge, REM sleep, and PGO waves following the experimental perturbations of the sleep cycle. Since forced locomotor activity is known to powerfully alter the timing of sleep and wakefulness, the present experiments used forced activity in an attempt to dissociate DRN discharge from the sleep cycle. It was hypothesized that such dissociations would suggest DRN discharge is not involved in sleep cycle regulation. Contrastingly, preserved correlations would support the hypothesis of a possible causal relationship between DRN discharge, PGO waves activity, and the timing of sleep and wakefulness. Extracellular recordings were obtained from single cells in the DRN of intact, undrugged cats across greater than 300 sleep cycles with durations ranging from about 8 to 80 mins. Forced activity significantly reduced the amount of time spent in wakefulness and increased the number but not the duration of REM sleep epochs. The results revealed that DRN discharge rate was altered as a function of sleep cycle duration. In no case, however, was forced activity able to completely dissociate the characteristic DRN discharge rates from PGO waves or the ultradian sleep cycle. The inability of forced activity to disrupt the faithful relationships between DRN discharge, PGO waves, and sleep cycle phase thus provides a new form of correlative evidence consistent with the hypothesis that the DRN is involved in sleep cycle regulation.

Animals↗

PubMed1987

Serotonin neurons and sleep. II. Time course of dorsal raphe discharge, PGO waves, and behavioral states.

This study documents the time course profiles for simultaneous measures of: the electrographic signs of sleep and wakefulness, ponto-geniculo-occipital (PGO) waves, and extracellular discharge potentials for single cells in the dorsal raphe nucleus (DRN). These measures were obtained from intact, undrugged cats across 177 sleep cycles. Ninety-one of these sleep cycles were recorded with no prior forced activity. Forced activity previously has been shown to powerfully alter the temporal organization of sleep by shortening the duration of both the sleep cycle and the ultradian rhythm of DRN discharge. The present paper evaluated the hypothesis that DRN discharge time course might regulate the sleep cycle. These experiments documented the phase relationship between the time course of DRN discharge and the electrographic signs of sleep. These phase relationship were examined by determining whether forced locomotor activity could dissociate the time course profile for behavioral states, PGO waves, and DRN discharge. The results revealed that the time course of DRN discharge and PGO waves were always phase-locked to the time course of the ultradian sleep cycle. Furthermore, the results show that changes in DRN discharge consistently precede changes in PGO waves, and behavioral state. Since a cause must precede an effect, these data are consistent with the hypothesis that the DRN may be causally involved in sleep cycle regulation. These temporal data also provide parameter values for the continued evaluation of cellularly based, mathematical models of sleep cycle control.

Action Potentials↗

PubMed1985

Forced internal desynchronization between circadian temperature and activity rhythms in squirrel monkeys.

In an attempt to force internal desynchronization between the rest-activity rhythm and the body temperature rhythm of the squirrel monkey (Saimiri sciureus), five animals were studied in a 14:14 light-dark cycle. In four animals a 28-h spectral component was found to predominate in the rest-activity rhythm, whereas an unentrained circadian component (tau = 25.9 +/- 0.4 h) predominated in the body temperature rhythm. Plots of the cycle-by-cycle acrophases of the two rhythms confirm that they desynchronize, due to the failure of the temperature rhythm to entrain to the light-dark cycle. These data from intact animals provide further support for the hypothesis that the squirrel monkey circadian timing system has at least two pacemakers. A rhythm for which the supra-chiasmatic nuclei (SCN) have previously been shown to be essential (rest-activity) simultaneously exhibited a different period from a rhythm (body temperature) that has been shown to persist after destruction of the SCN.

Animals↗

PubMed1984

Role of the suprachiasmatic nuclei in the circadian timing system of the squirrel monkey. I. The generation of rhythmicity.

The circadian organization of squirrel monkey (Saimiri sciureus) drinking behavior was evaluated before and after the placement of radiofrequency lesions which completely destroyed the suprachiasmatic nuclei (SCN) in 4 monkeys and partially ablated the SCN in another 4 animals. In continuous illumination (LL: 600 lux) prior to surgery, each monkey had a precise free-running circadian rhythm of drinking behavior with a period of 25.31 +/- 0.21 h (means +/- S.E.M.). By 4-6 weeks following the lesions, the temporal organization of drinking behavior had become disrupted, but a statistically significant free-running circadian rhythm was still detectable by time series analyses. Subsequently, the circadian organization of drinking behavior in 7 out of 8 monkeys gradually decayed with either no statistically significant rhythmicity or only weak circadian and/or ultradian rhythmicity detected by time series analyses by 10-92 weeks post-lesion. The remaining animal which maintained a statistically reliable free-running rhythm in drinking behavior received the least damage (less than 50%) to the SCN. Despite the major alterations in the temporal patterning of behavior, the overall amount of drinking behavior per 24 h was unchanged. The SCN are thus essential for maintaining the circadian organization of squirrel monkey drinking behavior. However, the existence of residual circadian rhythmicity following SCN lesions and the gradual decay of circadian organization thereafter suggest that the SCN may coordinate the activity of circadian oscillators which lie outside its borders.

Animals↗

PubMed1984

Role of the suprachiasmatic nuclei in the circadian timing system of the squirrel monkey. II. Light-dark cycle entrainment.

The role of the suprachiasmatic nuclei (SCN) in light-dark (LD) cycle entrainment in the squirrel monkey (Saimiri sciureus) was evaluated by continuously monitoring core body temperature and drinking behavior in both intact and SCN-lesioned animals exposed to different LD conditions. In a 24-h LD cycle with 12 h of light per day (LD 12:12), both intact and SCN-lesioned monkeys had a prominent rhythm in body temperature with an acrophase 6.51 +/- 0.36 h (intact) or 5.12 +/- 0.42 h (SCN-lesioned) after light onset. In a 23-h LD cycle composed of 1 hr of light and 22 h of dark (LD 1:22), the temperature rhythm in both intact and SCN-lesioned monkeys became synchronized with the 23-h period of the LD cycle. Studies examining the effects of LD cycle exposure on the temporal pattern of drinking behavior indicated that both intact and SCN-lesioned monkeys confined their drinking to the daily period of light. Each monkey was subsequently exposed to an LD cycle with 6 h of bright light and 18 h of darkness or dim background illumination (i.e. 60:0, 66:6 and 76:16 lux cycles). In intact monkeys systematic increases in the average intensity of the daily LD cycle produced corresponding delays in the phase of the daily offset of drinking behavior but did not alter the basic 24-h rhythmicity in the behavior. In contrast, increasing the intensity of the 24-h LD cycle in SCN-lesioned monkeys produced no delay in the daily termination of drinking, but instead produced a disintegration in the 24-h rhythm of drinking behavior.(ABSTRACT TRUNCATED AT 250 WORDS)

Animals↗

PubMed1984

Human brain contains vasopressin and vasoactive intestinal polypeptide neuronal subpopulations in the suprachiasmatic region.

The suprachiasmatic nuclei (SCN) and retinohypothalamic tract ( RHT ) in the anterior hypothalamus have been postulated to play an important role in the timing of daily biological rhythms in mammals. Although physiological studies have described circadian rhythms in man, the presence of an RHT or SCN has not been conclusively demonstrated in the human brain. Immunocytochemical identification of distinct ventral vasoactive intestinal polypeptide (VIP) containing and dorsal vasopressin containing neuronal subpopulations in the human suprachiasmatic region provides correlative evidence of neuronal clusters which are homologous to discrete cell groups in the SCN of other mammalian species. Manipulation of the circadian system has been used to treat some affective illnesses and other physiological timing disorders. Characterization of the neural substrates underlying human circadian rhythms could be useful in the development of future treatment modalities and is essential for understanding normal human circadian organization.

Afferent Pathways↗

PubMed1984

Forced activity alters sleep cycle periodicity and dorsal raphe discharge rhythm.

Single-cell activity recorded from the brain stem dorsal raphe nucleus (DRN) of cats showed a regular firing pattern during wakefulness (2-3 spikes/s), decreased activity during slow-wave or synchronized sleep (1 spike/s), and cessation of regular discharge during desynchronized sleep (0.05 spikes/s). DRN discharge was negatively correlated with the onset and maintenance of the polycyclic desynchronized sleep rhythm. These findings were derived from analyses of DRN firing rate sampled during different behavioral states. The present time-course analyses of DRN discharge described for the first time the period, amplitude, and phase characteristics of DRN activity relative to the timing of behavioral states that comprise the complete sleep cycle. The time course of both DRN discharge and the occurrence of wakefulness, slow-wave (S) sleep, transition, and desynchronized (D) sleep were behaviorally manipulated. Forced locomotor activity imposed by a treadmill task shortened the period length of the sleep cycle and the duration of the DRN discharge cycle. The magnitude and direction of these shifts in period length were consistent across multiple sleep cycles, and there was a high degree of coherence between the period length of the sleep cycle and the DRN discharge profiles. The DRN discharge rate also displayed phase dependence within S and D sleep. These results support the hypothesis that the DRN has a physiological role in regulating the timing of the ultradian sleep cycle.

Animals↗

PubMed1983

The time-course of dorsal raphe discharge, PGO waves, and muscle tone averaged across multiple sleep cycles.

Long-term recordings of dorsal raphe (DRN) activity were obtained from cats chronically implanted with microwires. The continuous time-course of DRN discharge, PGO waves, and muscle tone was quantified across multiple sleep cycles. DRN activity profiles were inversely correlated with PGO waves, biphasically related to muscle tone, and varied with sleep cycle phase. The role of DRN as a putative regulator of behavioral state and/or specific physiological variables is discussed.

Animals↗

PubMed1983

Enhancement of dorsal raphe discharge by medial pontine reticular formation stimulation depends on behavioral state.

Single cell activity was recorded with microwire electrodes from the dorsal raphe nucleus (DRN) of cats across multiple cycles of sleep and wakefulness. Electrical stimulation of the medial pontine reticular formation (mPRF) produced a 10-fold enhancement of DRN discharge during wakefulness and slow wave sleep but not during desynchronized sleep. The neuronal mechanisms likely to mediate the state-dependent effects of mPRF stimulation are discussed with regard to the hypothesis that DRN plays a major role in behavioral state control.

Animals↗