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Biomedical subjects

J A Hobson

Publications and source records attributed to J A Hobson.

At least 73 records · Page 4Linked to original sources
PubMed1989

Mapping neuronal inputs to REM sleep induction sites with carbachol-fluorescent microspheres.

The cholinergic agonist carbachol was conjugated to latex microspheres that were fluorescently labeled with rhodamine and used as neuroanatomical probes that show little diffusion from their injection site and retrogradely label neurons projecting to the injection site. Microinjection of this pharmacologically active probe into the gigantocellular field of the cat pontine brain stem caused the awake cats to fall into rapid movement (REM) sleep indistinguishable from that produced by free carbachol. Three-dimensional computer reconstruction of the retrogradely labeled neurons revealed a widely distributed neuronal network in the pontine tegmentum. These pharmacologically active microspheres permit a new precision in the characterization and mapping of neurons associated with the control of behavioral state and of other cholinergic networks.

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

Nightcap: a home-based sleep monitoring system.

In an attempt to offer a home-based adjunct to traditional sleep laboratory methods, we developed a system to monitor sleep, and to predict algorithmically non-rapid-eye-movement (NREM) and rapid-eye-movement (REM) sleep states, using eye and body motility as the only parameters. Eye movement was measured using a strain gauge transducer applied to the eyelid of subjects, while body movement was measured using a piezo-ceramic phono cartridge. Both transducers were mounted on a tennis headband, along with electronics that amplified, filtered, and digitized the signals. Digital pulse signals were input to a portable computer in minute-long epochs, and state-predicting algorithms were run based on this motility data. Four subjects were monitored in the sleep lab with both our headgear and standard polysomnography. Hand-scored sleep records were compared with those predicted by computer algorithms. Algorithm-predicted states agreed with hand-scored ones an average of 85.57% (SEM +/- 1.7%). Mean values for sleep onset and REM latency were within 1.6 and 10.8 min of polysomnographic records, respectively. These results are encouraging, and suggest that this system could provide a comfortable, subject operable, and inexpensive method for the evaluation of sleep at home.

Adult↗
PubMed1988

Differential enhancement of rapid eye movement sleep signs in the cat: a comparison of microinjection of the cholinergic agonist carbachol and the beta-adrenergic antagonist propranolol on pontogeniculo-occipital wave clusters.

The cholinergic agonist carbachol and the beta-adrenergic antagonist propranolol were microinjected at the same pontine sites and their effects on polygraphic rapid eye movement (REM) sleep, especially pontogeniculo-occipital (PGO) waves, were measured. While both propranolol and carbachol enhanced PGO wave activity and polygraphic REM sleep, the carbachol-correlated enhancement was more impressive. The increases in REM sleep signs elicited by carbachol were 5-fold over baseline and lasted throughout the 4-h recording period. Propranolol elicited 2.5-fold increases that were significant in the first 2 h only. Yet, the increase in PGO wave activity evoked by propranolol was equal to that of carbachol during non-REM sleep and wakefulness. The results indicate that while propranolol is less potent in activating the distributed neuronal network responsible for REM sleep generation, it selectively facilities that part of the network responsible for PGO waves.

Adrenergic Fibers↗
PubMed1988

A microcomputer-based system for automated EEG collection and scoring of behavioral state in cats.

A data acquisition and analysis system based on an Apple II microcomputer has been developed for use in sleep studies in the adult cat. The system reliably counts delta, spindle, and EMG waveforms, PGO waves, and REMs using amplitude and frequency criteria. These data can be used to algorithmically score sleep-wake state with high reliability (greater than 90% agreement with manual scoring). This method allows for automatic and quantitative analysis of selected EEG waveforms and sleep-wake states with less expense, more time savings, and greater convenience than manual scoring.

Animals↗
PubMed1988

Brain state and plasticity: an integration of the reciprocal interaction model of sleep cycle oscillation with attentional models of hippocampal function.

The present paper relates the reciprocal interaction model for sleep cycle oscillation (McCarley and Hobson, ref. 29) to an attentional model of hippocampal function (Schmajuk and Moore, ref. 44). We consider mechanisms by which the interaction between gigantocellular tegmental field (FTG) cells and locus coeruleus (LC) activity proposed by the sleep cycle model may differentially modulate the information processing carried out in the hippocampus as described by the attentional model. Our fundamental assumption is that learning about the relevancy of different stimuli is proportional to the level of LC activation. If the environment becomes unpredictable during waking, the FTG and LC are activated and the LC facilitates hippocampal learning about stimulus relevancy. In a predictable situation during waking, FTG cells discharge rarely because no novelty is detected, and LC neurons are moderately active. If the predictable situation lasts, LC cells also decrease their activity, and a sleep period might start. At sleep onset, LC inhibition decreases and FTG activity is low leading to slow sleep. As FTG activity increases and LC activity reaches its low point, REM sleep starts. Because LC activity is low during REM sleep, values of stimulus relevancy remain unchanged. Since during sleep the threshold for external stimuli is high, only internally generated novel stimuli (subjectively perceived as dream mentation) may activate the LC. LC renewed inhibitory influence on the FTG ends REM sleep.

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

A neuroanatomical gradient in the pontine tegmentum for the cholinoceptive induction of desynchronized sleep signs.

Microinjection of cholinergic agonists into the pontine tegmentum was used to evoke a state which was polygraphically and behaviorally similar to desynchronized (D) sleep. This study was designed to test the hypothesis that the production of this pharmacologically induced D sleep-like state (D-ACh) was dependent upon the anatomical locus of drug administration within the pontine tegmentum. Four dependent variables of D sleep were measured: D latency, D percentage, D duration and D frequency. Multiple regression analysis and analysis of variance were performed to evaluate the relationship between the three-dimensional coordinates of the injection site (posterior, vertical and lateral) and these 4 dependent measures. The intrapontine site of drug administration accounted for a statistically significant amount of the variance in D latency, D percentage and D duration. There was no significant relationship between the anatomical site of saline injection and the dependent measures of D sleep. A significant increase in D frequency following microinjection of cholinergic agonists was found to be independent of injection site. Pontine injection sites which yielded the shortest D latencies were found to be the same sites from which the highest D percentages were evoked. Rostrodorsal pontine tegmental injection sites were most effective in producing the highest percentages of D-ACh with the shortest latencies to onset. Injections made more caudally and ventrally within the pontine tegmentum produced lower percentages of D-ACh with longer latencies to onset. These data suggest the existence of an anatomical gradient within the pontine tegmentum for the cholinoceptive evocation of a D sleep-like state, and further support the concept that D sleep is generated, in part, by pontine cholinergic mechanisms.

Acetylcholine↗
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

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↗
PubMed1987

Dream bizarreness and the activation-synthesis hypothesis.

The unusual aspect of dream consciousness which has been called "dream bizarreness" may be defined as impossibility or improbability in the domains of dream plot, cognition and affect. The bizarre features of dreams may be divided into three broad categories: discontinuities, incongruities and uncertainties. Discontinuities are interruptions in orientational stability; incongruities are inappropriate syntheses of mismatching plot elements; uncertainties are confusions of distinct conceptions. Dream bizarreness appears to be the manifestation of some state-dependent cognitive process which is probably rooted in REM sleep neurophysiology. In the waking state, our brain/minds are capable of remaining focused on the normal flow of ongoing information, and such features of life as plot and time unfold in a linear sequence. In REM sleep/dreaming, this function appears to be interfered with, and disparate elements of consciousness are suddenly interjected as the brain/mind cannot maintain its orientational focus in the usual way.

Arousal↗
PubMed1984

Site-specific enhancement and suppression of desynchronized sleep signs following cholinergic stimulation of three brainstem regions.

The behavioral effects of carbachol microinjection into the pontine, midbrain and medullary reticular formation (RF) have been studied. Enhancement of electrographic desynchronized (D) sleep signs and D sleep-like behavior was specific to the pons; these parameters were contrastingly suppressed following cholinergic stimulation of the midbrain and medullary RF. Polygraphically defined wakefulness (W) was increased from the midbrain and medulla and was characterized by stereotyped motor activity, whereas slow wave (S) sleep was reduced or eliminated when carbachol was administered into all 3 brainstem regions. In addition, as a function of the site of carbachol administration within the pons, some qualitative electrographic differences between carbachol-induced D sleep and the physiological D sleep state were observed. These results are consistent with the hypotheses that the pontine RF is involved in the cholinergic initiation and/or maintenance of D sleep and that the midbrain RF mediates arousal via cholinoceptive reticular cells. The hypothesis that the medullary RF plays a major role in the generation of S sleep and the atonia of D sleep is not supported by these data, but non-cholinergic mechanisms of these proposed roles remain to be investigated. Preliminary reports of these data have been published.

Animals↗
PubMed1984

Long term stability of rat sleep quantified by microcomputer analysis.

An inexpensive microcomputer system is described for the direct recording of electrographic data from animals. Using this system, electrographic data can be recorded continuously on a polygraph and simultaneously quantitated by the computer, for days or weeks. Our system quantifies the amounts of delta waves, spindle bursts, hippocampal RSA activity and movement spikes for 15 sec epochs. These electrographic data are stored by the computer and subsequently can be used to score sleep stages. We find that the computer reliably counts waves; using these data, it can then score sleep stages off-line with about 90% accuracy. With this system, we find that the minutes/hour of both SWS and REM are remarkably stable from day to day. The absolute number of delta waves, spindle bursts, trains of RSA and movement counts/hour also remain stable from day to day. This type of system should find significant application in situations where quantitation of longterm effects of drugs, diets and other environmental inputs on sleep states or EEG wave bands are of interest.

Animals↗
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↗