Ponto-geniculo-occipital Waves Research Articles

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 (>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.

The blockage of ponto-geniculo-occipital waves in the cat lateral geniculate nucleus by nicotinic antagonists

The cholinergic mechanism underlying the genesis of ponto-geniculo-occipital (PGO) waves recorded from the lateral geniculate (LG) nucleus was studied in reserpinized cats under urethane anesthesia. PGO field potentials and their related unit activities occured spontaneously or were triggered by stimulation of the brainstem peribrachial (PB) area. It was found that PGO-related unit activities were strongly depressed by systemic or iontophoretic applications of nicotinic antagonists such as mecamylamine or hexamethonium but remained intact after similar applications of scopolamine. These results suggest that the genesis of thalamic PGO waves involves a nicotinic activation of relay neurons by PB cholinergic afferents.

Etude electrophysiologique de la tianeptine, nouveau stimulant du recaptage de la serotonine possedant une activite antidepressive

Tianeptine is a clinically effective antidepressant, not chemically related to classical tricyclic compounds. Its mechanism of action preferentially involves central serotoninergic transmissions, by increasing uptake after acute and chronic administration in rat brain and platelets and in human platelets. We studied the effects of tianeptine on three currently used electrophysiological methods: Ro4-1284 induced PGO waves in the cat, neocortical EEG activity in the acute rat preparation and sleep-wakefulness modifications in chronically implanted rats. Density of Ro4-1284 induced PGO waves was reduced by tianeptine, the minimal effective dose being 2 mg.kg-1i.v. (ED50 = 2.9 mg.kg-1i.v.). In acute rat preparation, the low voltage fast waves basal EEG pattern was not modified by tianeptine in a dose range of 1.25 to 20 mg.kg-1i.p. Higher dosage (25 mg.kg-1i.p.) induced high amplitude episodes with few or no delta waves. Low doses which did not apparently modify acute EEG have been tested on sleep-wakefulness cycle in implanted rats. Tianeptine, after single administration, did not modify sleep states up to 2.5 mg.kg-1i.p. An increased wakefulness was observed during the first hour after 5-10 mg.kg-1i.p., afterwards sleep states returned to control values up to 12 h. A subsequent 12 h recording performed 24 h after treatment did not show any change compared to pretreatment baseline. After sub-chronic administration (2.5 mg.kg-1i.p./day, 9 days) no change was observed in sleepwake pattern during or after cessation of treatment. Tianeptine EEG profile is radically different from those usually induced by classical tricyclic antidepressants.

Antagonizing effects of YM-14673, a new TRH derivative, on behavioral and electroencephalographic changes in reserpinized animals.

Effects of YM-14673 (N alpha-[[S)-4-oxo-2-azetidinyl)-carbonyl]-L-histidyl-L-prolinamide dihydrate), a new TRH derivative, on reserpine-induced behavioural and electroencephalographic changes were observed in comparison with those of TRH. YM-14673 antagonized reserpine-induced hypothermia and decrease in convulsion threshold in mice. The number of PGO waves recorded from the lateral geniculate body was decreased by administration of YM-14673 in reserpinized cats. The anti-reserpine activity of intravenous YM-14673 was about 8-20 times more potent than that of TRH. In inhibiting reserpine-induced hypothermia, the oral ED2 degrees C relative to IV ED2 degrees C as an indirect indication of absorption rate of the drugs was 15 for both YM-14673 and TRH. These results suggest that YM-14673 possesses more potent facilitatory effects on the central monoamine systems than TRH.

Reticular control of thalamic transmission during behavioral states: A study in dorsal lateral geniculate nucleus relay neurons of the cat

In behaving cats adapted to head restraint we examined the changes of spontaneous activity of dorsal lateral geniculate relay neurons provoked by weak stimulation of mesencephalic reticular formation during different states of sleep and alertness. The neurons were classified as fast- and slow-conducting neurons depending on their optic tract latency. When the reticular stimulation was delivered during slow-wave sleep, it increased the firing rate principally in slow neurons and suppressed the burst pattern. The increases occurred on a long depolarization in intracellular recordings ( n = 9). The effect resembled one that was simultaneous with pontogeniculooccipital waves. Only slow neurons showed a correlation between the relative increases and the prestimulus firing rate. The excitatory effect was reduced and less frequent during wakefulness and paradoxical sleep in both latency groups. When reticular stimulation did not influence the spontaneous activity of the activated states, it also did not modify the optic tract-elicited hyperpolarization. The data tend to demonstrate that the efficiency of the reticular stimulation depends principally on the rat and pattern of the spontaneous activity which, itself, varies largely according to the behavioral state and moderately according to the optic tract latency.

Distribution of choline acetyltransferase immunoreactive somata in the feline brainstem: implications for REM sleep generation.

In the present study we examined the distribution of cholinergic and catecholaminergic neurons, in the feline brainstem, as defined by choline acetyltransferase (ChAT) and tyrosine hydroxylase (TH) immunohistochemistry. In the dorsal tegmentum, ChAT immunoreactive neurons were distributed in the parabrachial area [the pedunculopontine group (PPG)] and along the medial adjacent central gray [the lateral dorsal tegmental group (LDT)]. The cholinergic neurons in the LDT area were larger than those in the PPG. When adjacent tissue sections were labeled with TH we noted extensive overlap between catecholamine and cholinergic neurons in the PPG, suggesting that REM sleep may occur as a result of an interaction between these transmitters in this area rather than the medial pontine reticular formation where no cholinergic or catecholamine neurons were found. Cholinergic neurons were also found in the cranial nerve nuclei and the nucleus ambiguus. The presence of cholinergic neurons in the PPG and LDT suggest that these neurons may play an important role in the generation of some of the tonic and phasic components of REM sleep, such as cortical desynchronization, pontogeniculo occipital waves, and muscle atonia.

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.

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.

Sleep abnormalities with REM disorder in experimental Creutzfeldt-Jakob disease in cats: a new pathological feature

Alterations in sleep organization were studied during the clinical phase of experimental Creutzfeldt-Jakob disease (CJD) in cats. Twenty months after intracerebral inoculation of a CJD agent, cats developed clinical signs including behavioral changes, diminished grooming activity, dysmetria, startle reflex, myoclonus, and unusual sleep abnormalities. Rapid eye movement (REM) sleep displayed a new and irreversible, organization, with a cotinuous and constant pseudoperiodic pattern of rapid eye movements, synchronous with diffuse bursts of cortical abnormalities and with ponto-geniculo-occipital (PGO) wave activity. Computer analysis revealed a constant morphology of cortical bursts and their temporal relationship with ocular episodes. Induction of PGO wave activity with benzoquinolizine derivative Ro 4-1284 demostratedd the PGO-dependent nature of the cortical alterations. Abnormal unresponsive states were observed during REM sleep phases and arousal thresholds were increased in CJD cats during REM sleep. The percentages of wakefulness and slow-wave sleep were reversed in these animals. Preliminary neuropathological observations included discrete to minimal spongiosss of cerebral gray matter and a remarkably focalized intracytoplasmic vacuolation in neurons of the raphésystem. Our findings suggest that particular neuronal systems involved in sleep regulation are impaired in CJD cats.

Lesion of the ponto-geniculo-occipital pathways in kittens. I. Effects on sleep and on unitary discharge of the lateral geniculate nucleus

Suppression of geniculate ponto-geniculo-occipital (PGO) waves was achieved in kittens by performing bilateral mesencephalic lesions of the PGO pathways. Sleep-wake parameters and the spontaneous unit activity in the lateral geniculate nucleus (LGN) were then chronically recorded during one month after the lesions. Whereas the states of vigilance remained normal, a significant reduction of the unitary discharge in the LGN during paradoxical sleep (PS) and particularly of its phasic component, was observed concomitantly with the suppression of PGO waves. It is concluded that phasic discharge of LGN neurons during PS is controlled by PGO-related mechanisms and that its suppression during the developmental period provides a model for studying its significance on brain maturation.

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.

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.

Firing properties of two types of nucleus raphe dorsalia neurons during the sleep-walking cycle and their responses to sensory stimuli

Spontaneous activity of the nucleus raphe dorsalis (NRD) neurons during the sleep-walking cycle and effects of sensory stimuli upon NRD neurons were studied in cats. Seventy-one neurons recorded within the NRD were classified into two groups with the use of the coefficient of variation of firing intervals during walking (W): 41 regularly firing (clock-like) and 30 irregularly firing (non-clock-like) neurons. The majority of clock-like and one-third of non-clock-like neurons showed a decrease in their firing rate during slow-wave sleep (SWS) compared with W. All neurons of both types displayed their lowest level of activity during paradoxical sleep. During the late phase of SWS, many clock-like neurons reduced their firing prior to the occurence of pontogeniculo-occipital waves, whereas non-clock-like neurons did not show such a specific property. Clock-like neurons were totally unresponsive to nociceptive and non-nociceptive somesthetic stimuli, while about half of the non-clock-like neurons were driven by these stimuli. Half of the clock-like and one-third of the non-clock-like neurons were driven by click stimulation, and the majority of them showed an excitatory response. Some of the clock-like and non-clock-like neurons exhibited inhibitory and excitatory response to flash stimulation, respectively. The results of this experiment show that two types of neurons do exist in the NRD and suggest that they play a functionally different role in the brain.

Relationships between pontogeniculooccipital waves and ocular movements

Relationships between pontogeniculooccipital waves and ocular movements

Activity of serotonin-containing neurons in nucleus raphe magnus in freely moving cats

Serotonergic neurons were recorded in the nucleus raphe magnus in freely moving cats and were initially identified on-line by their characteristic slow and regular spontaneous activity during quiet waking (3.42 ± 0.33 spikes/s; mean ± SE). Discharge rates of these serotonergic neurons were highest during active waking (4.49 ± 0.40 spikes/s), intermediate during slow-wave sleep (middle: 2.14 ± 0.23 spikes/s), and lowest during REM sleep (0.20 ± 0.03 spikes/s). Although these cells fired at a rate 31.3% higher during active waking than during quiet waking, their activity displayed no correlation with phasic elevations of the nuchal EMG or overt body movements. In addition, no relationship was observed between the activity of these neurons during slow-wave sleep and the occurrence of sleep spindles in the cortical EEG or pontogeniculooccipital waves recorded from the lateral geniculate nucleus. Serotonergic neurons of nucleus raphe magnus were also relatively unresponsive to phasic auditory and visual stimuli, with about half of the cells examined showing weak excitatory responses. These neurons did respond, however, to the administration of a small dose of the serotonin specific agonist, 5-methoxy- N,N-dimethyltryptamine (250 μg/kg, i.m.) with a mean decrease in unit activity of 73.6 ± 4.5%. The results of this study are compared with those previously reported for serotonergic neurons in the dorsal raphe nucleus, nucleus centralis superior, and nucleus raphe pallidus of freely moving cats.

Variability in the characteristics of pontogeniculooccipital spikes during paradoxical sleep

An important criterion for identifying paradoxical sleep is the presence of a peculiar waveform recorded in the pons, lateral geniculate body, and visual cortex during that sleep state. These waveforms, termed PGO waves, have long been viewed as having large and constant amplitudes, an initial negative deflection in the visual cortex, and not being dependent on the levels of background illumination. Waveforms recorded during wakefulness have different characteristics, and these have been used to differentiate the waking state from paradoxical sleep. The present study demonstrated that most PGO waves have highly variable amplitudes during paradoxical sleep and that only a small fraction conform to the stereotypic wave characteristics of constant and large amplitudes and the presence of initial negative deflections. These findings argue against the criteria commonly used to differentiate PGO waves during paradoxical sleep from the eye movement potentials recorded in wakefulness.

Effects of chronic administration of D-amphetamine on PGO wave activity in the cat

The effects of depletion of serotonin by the chronic administration of amphetamine (twice daily, 7.5 mg/kg per injection on days 1–6; 15 mg/kg per injection on the remaining days, i.p.) for 10–14 days on ponto-geniculo-occipital (PGO) waves was examined in cats. While the regimen of pretreatment with amphetamine produced comparable decreases in the content of central serotonin (i.e. 40–70%) to those observed in other studies (i.e. with reserpine, p-chlorophenylalanine, methiothepin) of pontogeniculo-occipital wave activity, no ponto-geniculo-occipital waves of the rapid-eye-movement sleep type were observed during waking after chronic treatment with amphetamine. These results are discussed within the context of the “serotonin gating” hypothesis of the generation of pontogeniculo-occipital waves, an hypothesis which states that ponto-geniculo-occipital waves emerge into waking when a critical level of the depletion of serotonin is reached, thus opening the “gate” for ponto-geniculo-occipital waves to enter waking states. The present authors suggest that a gradual depletion of serotonin, such as occurs following the chronic administration of amphetamine, will not elicit ponto-geniculo-occipital waves into waking, whereas a rapid depletion of serotonin, such as occurs following treatment with reserpine, results in the emergence of ponto-geniculo-occipital waves into waking.

Suppression of PGO waves in the kitten: Anatomical effects on the lateral geniculate nucleus

Bilateral mesencephalic electrolytic lesions were performed in 2-week-old kittens, in order to suppress the ascending ponto-geniculo-occipital activity. The subsequent anatomical development of the lateral geniculate nucleus was analyzed. A significant maturational deficit was evidenced in 5-week-old experimental kittens as compared to age-paired controls. It is concluded that a lesion in the X area impairs the maturation of CNS. The relationship between this area (the phasic components of paradoxical sleep) and the maturation of CNS are still to be demonstrated.

REM sleep burst neurons, PGO waves, and eye movement information.

Pontogeniculooccipital (PGO) waves appeared almost simultaneously in both lateral geniculate nuclei (LGB), but in each case on had a larger amplitude and preceded the other by a few milliseconds. The larger, earlier wave is called the primary wave. Primary waves were found to appear with equal frequency in each LGB. During rapid eye movement sleep (REM sleep), LGB primary waves were ipsilateral to the direction of rapid eye movements. During REM sleep a group of cat midbrain neurons, which we call PGO burst cells, fired in stereotyped bursts at fixed latencies before ipsilateral primary waves, but they almost never fired bursts when the primary waves were contralateral. PGO burst neuron discharge also correlated with the direction of rapid eye movements during REM sleep. In wakefulness, PGO burst cells fired single spikes, not bursts, which had some correlation with LGB waves when averaged by computer. The results suggest that PGO burst cells are output elements in the PGO wave-generation system ad that PGO waves convey eye movement information to the sensory visual system in REM sleep. They also may have a role in the production of saccade-related waves in the visual system during wakefulness.

PGO waves in rats in the non-paradoxical sleep states

Experiments were conducted in rats in order to characterize further the occurrence of PGO waves recorded from the region of the locus coeruleus, which were elicited by auditory stimuli. Repeated stimulus presentations at regular interstimulus intervals resulted in a consistent, state-dependent pattern in the occurrence and amplitudes of elicited PGO waves. The probability of eliciting a PGO wave was lowest during paradoxical sleep and highest immediately afterwards. This was followed by a gradual decline in responding during the ensuing period of slow-wave sleep. These results were obtained regardless of at what point in the rats' sleep cycles presentations of the auditory stimuli began. In other experiments, a comparison of elicited PGO waves with the acoustic startle reflex revealed major differences between these 2 responses. PGO waves could be elicited with very low intensity stimuli that were below the threshold for producing a behavioral response, while much louder stimuli were required to elicit a startle. The startle reflex habituated in a linear fashion and did not display state-related changes. It was concluded that elicited PGO waves are an electrophysiological sign of sensory responsiveness, and that their spontaneous appearance during and preceding paradoxical sleep reflects endogenously generated reticular activation.