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J A Hobson

Publications and source records attributed to J A Hobson.

At least 19 recordsLinked to original sources
PubMed1992

Sleep and dreaming: induction and mediation of REM sleep by cholinergic mechanisms.

The most important recent work on the neurobiology of sleep has focused on the precise cellular and biochemical mechanisms of rapid eye movement sleep mediation. Direct and indirect evidence implicates acetylcholine-containing neurons in the peribrachial pons as critical in the triggering and maintenance of rapid eye movement sleep. Other new studies provide support for the hypothesis that the cholinergic generator system is gated during waking by serotonergic and noradrenergic influences. A growing consensus regarding the basic neurobiology has stimulated new thinking about the brain basis of consciousness during waking and dreaming.

Acetylcholine↗
PubMed1992

Cholinergic microstimulation of the peribrachial nucleus in the cat. I. Immediate and prolonged increases in ponto-geniculo-occipital waves.

The cholinergic agonist carbachol was injected into the pontine Pb area where PGO bursting cells have been recorded. When microinjections were localized to the ventrolateral aspect of the caudal Pb nucleus near aggregates of ChAT immunolabeled cholinergic neurons, carbachol produced an immediate onset of state-independent PGO waves in the ipsilateral LGB. These state-independent PGO waves persisted for 3-4 days. After the first 24 hrs PGO wave activity increasingly became associated with REM sleep and with REM transitional SP sleep as both of these PGO-related states increased in amount to 3-4 times baseline levels. The increase in amount of PGO-related states peaked on days 2-4 following one carbachol injection and persisted for 10-12 days. These results suggest a two stage process: stage one, PGO enhancement, is the direct consequence of the membrane activation of cholinoceptive PGO burst neurons by carbachol; stage two, REM enhancement, is the consequence of metabolic activation of endogenous cholinergic neurons. This experimental preparation is a useful model for the study of the electrophysiology and functional significance of PGO wave and REM sleep generation.

Acetylcholine↗
PubMed1992

Cholinergic microstimulation of the peribrachial nucleus in the cat. II. Delayed and prolonged increases in REM sleep.

The hypothesis that REM sleep is cholinergically mediated is supported by the identification of a cholinoceptive trigger zone in the FTG. Since this trigger zone is devoid of cholinergic neurons, the aim of the present study was to test the hypothesis that a cholinergic drive for REM sleep may come from the cholinergic cells of the PBL region. Chronically implanted freely moving cats with electrodes for sleep and PGO wave recordings were used. Guide tubes were implanted for carbachol microinjections (4 micrograms/250 nl) in the PBL and FTG. All microinjections were delivered in close vicinity of ChAT+ cholinergic cells in the PBL region. Results showed that a single unilateral carbachol microinjection into the PBL induced sustained (24 hr) state-independent ipsilateral PGO wave activity. This PGO wave activity was followed by a prolonged enhancement of REM sleep lasting for more than six days. We also observed that REM enhancement was followed by a delayed but marked enhancement of S sleep episodes with PGO waves (SP), which are normally brief transitions from S to REM sleep. Our findings strongly support the hypothesis that cholinergic drive for REM sleep comes from the lateral pontine tegmentum and we suggest that the PBL region plays a major role in both PGO wave generation and long-term regulation of REM sleep induction.

Acetylcholine↗
PubMed1992

Dynamic suppression of REM sleep by parenteral administration of the serotonin-1 agonist eltoprazine.

The purpose of this study was to determine the effects of the serotonin-1 agonist eltoprazine on the control of rapid eye movement (REM) sleep. Continuous polygraph recordings were performed for 15-17 days in four adult male cats. During the first 5 control days cats received injections of 0.9% saline intraperitoneally (i.p.) twice per day (b.i.d.). Over the next 5-7 days cats received injections of 0.9% saline intraperitoneally (i.p.) twice per day (b.i.d.). Over the next 5-7 days cats received eltoprazine i.p. (1-2 mg/kg, b.i.d.). For the final 5 recovery days cats received saline alone. During the saline control period, the mean REM sleep percent was 13.8 +/- 0.91%. When eltoprazine was administered for the subsequent 5-7 days, the mean REM percent was reduced to 1.5 +/- 0.59%. During the 5-day recovery period, REM percent increased significantly (p less than 0.0001) above both control and drug injection values to a mean of 24.5 +/- 1.3% with a maximum on recovery day 1 of 28.4 +/- 2.6% (n = 4). In addition to REM suppression, eltoprazine produced other electroencephalographic changes: an increase in slow-wave sleep (S) percent without any change in overall wake (W) percent; an increase in electromyogram (EMG) amplitude; and a decrease in ponto-geniculo-occipital (PGO) wave activity. PGO wave frequency and REM% increased significantly during the recovery period. Thus our findings demonstrate REM and PGO suppression by eltoprazine and document dramatic rebound effects following its withdrawal.

Animals↗
PubMed1991

Automated staging of sleep in cats using neural networks.

Manual staging of sleep based on visual EEG criteria is a laborious and time-consuming task. In an effort to automate sleep staging, we have developed a neural network that 'learns' to stage sleep on the basis of wave band count data alone, in the cat. Wave band count data are collected on a microcomputer, using period-amplitude analysis. Delta waves, spindle bursts, ponto-geniculo-occipital (PGO) waves, electro-oculogram (EOG), basal electromyogram (EMG) amplitude, and movement artifact amplitude are collected, and used to 'train' the network to score sleep. These wave count data serve as the input patterns to the net, and the corresponding manually scored sleep stages serve as a 'teacher.' We demonstrate that, when used to score the states of wake, slow wave sleep (SWS), desynchronized sleep (D), and the transition period from SWS to D (SP), these neural networks agree with manual scoring an average of 93.3% for all epochs scored. Neural network programs can learn both rules and exceptions, and since the nets teach themselves these rules automatically, a minimum of human effort is required. Because programming requirements are small for neural nets, this approach is readily adaptable to microcomputer-based systems and is widely applicable to both animal and human EEG analyses. The utility of this approach for the detection and classification of a variety of clinical neurophysiological disorders is discussed.

Animals↗
PubMed1991

Developmental phases of sleep and motor behaviour in a cat mother-infant system: a time-lapse video approach.

The evolution of sleep patterns in developing kittens was studied using time-lapse video technology and direct observation. The duration, frequency, and onset of the behavioural states and interactions of the cats were analyzed and then organized into phases that represent major changes in developmental structure during the first 6 weeks of kitten life. We have demonstrated that the kittens began exhibiting adult bi-cyclic sleep patterns on approximately Day 30 of development. During the 10-day period that preceded this consolidation of sleep pattern, REM sleep decreased by half, with a reciprocal increase in NREM sleep. These changes were coincident with an increase in kitten patterned motor behaviour and an increase in stimulation of the kittens by the mother during her bi-cyclic active periods.

Animals↗
PubMed1991

Long-term enhancement of REM sleep following cholinergic stimulation.

A six day long increase in rapid eye movement (REM) sleep followed the unilateral microinjection of a single dose of the cholinergic agonist drug carbachol into the brain stem of cats. Effective drug injection sites were localized to the pontine peribrachial region containing cholinergic choline acetyltransferase (ChAT) labeled neurons. At the peak of the effect, which occurred 24-28 h post-injection, the relative amount of time devoted to REM sleep tripled, resulting in an absolute time increase from 3.12 to 11.28 h REM sleep per day. This pronounced and prolonged REM sleep increase was associated with marked enhancement of ponto-geniculo-occipital (PGO) waves and with PGO burst cell activity unilateral to the site of injection.

Analysis of Variance↗
PubMed1990

A cholinoceptive desynchronized sleep induction zone in the anterodorsal pontine tegmentum: locus of the sensitive region.

Carbachol, a long-acting cholinergic agonist, was microinjected (4 micrograms/250 nl per 90 s) into 90 sites within the anterodorsal pontine tegmentum of four cats and the time to onset and percentage of time spent in a desynchronized sleep-like state during 40 min postinjection were calculated. Compared with more posteroventral pontine sites, the shorter latencies and higher percentages observed confirmed earlier predictions of a sensitive cholinoceptive zone in the anterodorsal pons. In 27 trials a desynchronized sleep-like state was observed within 5 min; in 31 trials the latency was 5-10 min and in the remaining 32 trials, greater than 10 min. Plotting the desynchronized sleep-like state latency and the desynchronized sleep-like state percentage as a function of the three-dimensional coordinates revealed that injection sites with short latency (less than 5 min) and high percentage (greater than 80%) were concentrated between the coordinates of P 1.0 to 3.5 and V -3.5 to -5.5, at the lateral coordinate L 2.0. On the frontal plane, the short desynchronized sleep-like state latency and high desynchronized sleep-like state percentage sites begin in the pontine tegmental region just lateral to the ventral tegmental nucleus and extend 3 mm ventrocaudally. A regression plot of the data in sagittal plane 2.0 revealed a short latency axis, around which the short latency sites cluster, running in a slightly dorsoventral direction from about P 1.0 to V -4.0 to P 4.0 to V -5.5. This observation suggests that the sensitive zone might approximate a cylinder in shape, a hypothesis supported by the correlation of longer latencies and lower percentages at increasing radial distance from the axis. The non-linear relationship between cholinergic potency and distance from the short latency axis suggests that the desynchronized sleep-like state latency is a function of two factors; a variable diffusion-based delay of carbachol to distant neuronal populations involved in the desynchronized sleep-like state production, and a fixed recruitment-based delay following activation of neurons in the sensitive zone. Interpretation of these findings in light of earlier studies involving microstimulation of the pontine tegmentum argue in favor of a distributed network of discrete neuronal populations as the source of desynchronized sleep generation.

Animals↗
PubMed1990

A cholinoceptive desynchronized sleep induction zone in the anterodorsal pontine tegmentum: spontaneous and drug-induced neuronal activity.

The effect of carbachol microapplication (4 micrograms/250 nl per 90 s) on the discharge of neurons in the anterodorsal pons of four cats was studied using a newly devised microinjector-microelectrode assembly. Neurons were classified according to the magnitude of their discharge rate increases (or decreases) in physiological desynchronized sleep as desynchronized-on (or desynchronized-off) before injecting carbachol. When carbachol produced a desynchronized sleep-like state only half (15 out of 30) of the desynchronized-on cells were activated (desynchronized-on/desynchronized sleep-like state-on) while the other half were not (desynchronized-on/desynchronized sleep-like state-not on). Compared with the non-activated cells, the desynchronized-on/desynchronized sleep-like state-on cells had three features consistent with playing an active role in desynchronized sleep generation: these cells had a higher mean discharge frequency in desynchronized sleep and higher ratio of discharge frequency in desynchronized sleep compared with wakefulness; they did not fire in phase with electromyogram excitation of neck muscles; and they were concentrated in the short latency desynchronized sleep-like state induction zone described in the companion paper. The three-way correlation between the optimal anatomical site for short latency desynchronized sleep-like state induction, the selective neuronal discharge pattern in desynchronized sleep and the cholinergic activation pattern in the desynchronized sleep-like state suggest that we may have identified a neuronal population that is cholinoceptively activated as part of the physiological mechanism of desynchronized sleep generation.

Activity Cycles↗
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↗