Ponto-geniculo-occipital Waves Research Articles

The Ponto-Geniculo-Occipital (PGO) Waves in Dreaming: An Overview.

Rapid eye movement (REM) sleep is the main sleep correlate of dreaming. Ponto-geniculo-occipital (PGO) waves are a signature of REM sleep. They represent the physiological mechanism of REM sleep that specifically limits the processing of external information. PGO waves look just like a message sent from the pons to the lateral geniculate nucleus of the visual thalamus, the occipital cortex, and other areas of the brain. The dedicated visual pathway of PGO waves can be interpreted by the brain as visual information, leading to the visual hallucinosis of dreams. PGO waves are considered to be both a reflection of REM sleep brain activity and causal to dreams due to their stimulation of the cortex. In this review, we summarize the role of PGO waves in potential neural circuits of two major theories, i.e., (1) dreams are generated by the activation of neural activity in the brainstem; (2) PGO waves signaling to the cortex. In addition, the potential physiological functions during REM sleep dreams, such as memory consolidation, unlearning, and brain development and plasticity and mood regulation, are discussed. It is hoped that our review will support and encourage research into the phenomenon of human PGO waves and their possible functions in dreaming.

Rhythmicity in heart rate and its surges usher a special period of sleep, a likely home for PGO waves.

High amplitude electroencephalogram (EEG) events, like unitary K-complex (KC), are used to partition sleep into stages and hence define the hypnogram, a key instrument of sleep medicine. Throughout sleep the heart rate (HR) changes, often as a steady HR increase leading to a peak, what is known as a heart rate surge (HRS). The hypnogram is often unavailable when most needed, when sleep is disturbed and the graphoelements lose their identity. The hypnogram is also difficult to define during normal sleep, particularly at the start of sleep and the periods that precede and follow rapid eye movement (REM) sleep. Here, we use objective quantitative criteria that group together periods that cannot be assigned to a conventional sleep stage into what we call REM0 periods, with the presence of a HRS one of their defining properties. Extended REM0 periods are characterized by highly regular sequences of HRS that generate an infra-low oscillation around 0.05 Hz. During these regular sequence of HRS, and just before each HRS event, we find avalanches of high amplitude events for each one of the mass electrophysiological signals, i.e. related to eye movement, the motor system and the general neural activity. The most prominent features of long REM0 periods are sequences of three to five KCs which we label multiple K-complexes (KCm). Regarding HRS, a clear dissociation is demonstrated between the presence or absence of high gamma band spectral power (55–95 Hz) of the two types of KCm events: KCm events with strong high frequencies (KCmWSHF) cluster just before the peak of HRS, while KCm between HRS show no increase in high gamma band (KCmNOHF). Tomographic estimates of activity from magnetoencephalography (MEG) in pre-KC periods (single and multiple) showed common increases in the cholinergic Nucleus Basalis of Meynert in the alpha band. The direct contrast of KCmWSHF with KCmNOHF showed increases in all subjects in the high sigma band in the base of the pons and in three subjects in both the delta and high gamma bands in the medial Pontine Reticular Formation (mPRF), the putative Long Lead Initial pulse (LLIP) for Ponto-Geniculo-Occipital (PGO) waves.

Coupling of hippocampal theta and ripples with pontogeniculooccipital waves.

The hippocampus has a major role in encoding and consolidating long-term memories, and undergoes plastic changes during sleep1. These changes require precise homeostatic control by subcortical neuromodulatory structures2. The underlying mechanisms of this phenomenon, however, remain unknown. Here, using multi-structure recordings in macaque monkeys, we show that the brainstem transiently modulates hippocampal network events through phasic pontine waves known as pontogeniculooccipital waves (PGO waves). Two physiologically distinct types of PGO wave appear to occur sequentially, selectively influencing high-frequency ripples and low-frequency theta events, respectively. The two types of PGO wave are associated with opposite hippocampal spike-field coupling, prompting periods of high neural synchrony of neural populations during periods of ripple and theta instances. The coupling between PGO waves and ripples, classically associated with distinct sleep stages, supports the notion that a global coordination mechanism of hippocampal sleep dynamics by cholinergic pontine transients may promote systems and synaptic memory consolidation as well as synaptic homeostasis.

The Transition Between Slow-Wave Sleep and REM Sleep Constitutes an Independent Sleep Stage Organized by Cholinergic Mechanisms in the Rostrodorsal Pontine Tegmentum.

There is little information on either the transition state occurring between slow-wave sleep (SWS) and rapid eye movement (REM) sleep, as well as about its neurobiological bases. This transition state, which is known as the intermediate state (IS), is well-defined in rats but poorly characterized in cats. Previous studies in our laboratory demonstrated that cholinergic stimulation of the perilocus coeruleus α nucleus (PLCα) in the pontine tegmentum of cats induced two states: wakefulness with muscle atonia and a state of dissociated sleep we have called the SPGO state. The SPGO state has characteristics in common with the IS, such including the presence of ponto-geniculo-occipital waves (PGO) and EEG synchronization with δ wave reduction. Therefore, the aims of the present study were (1) to characterize the IS in the cat and, (2), to study the analogy between the SPGO and the different sleep stages showing PGO activity, including the IS. Polygraphic recordings of 10 cats were used. In seven cats carbachol microinjections (20–30 nL, 0.01–0.1 M) were delivered in the PLCα. In the different states, PGO waves were analyzed and power spectra obtained for the δ, θ, α, and β bands of the EEG from the frontal and occipital cortices, and for the θ hippocampal band. Statistical comparisons were made between the values obtained from the different states. The results indicate that the IS constitutes a state with characteristics that are distinct from both the preceding SWS and the following REM sleep, and that SPGO presents a high analogy with the IS. Therefore, the SPGO state induced by administering carbachol in the PLCα nucleus seems to be an expression of the physiological IS of the cat. Consequently, we propose that the PLCα region, besides being involved in the mechanisms of muscle atonia, may also be responsible for organizing the transition from SWS to REM sleep.

Sharply contoured theta waves are the human correlate of ponto-geniculo-occipital waves in the primary visual cortex

ObjectivePonto-geniculo-occipital (PGO) waves occurring along the visual axis are one of the hallmarks of REM sleep in experimental animals. In humans, direct evidence is scarce. There is no systematic study of PGO waves in the primary visual cortex. MethodsEleven epilepsy patients undergoing combined intracranial EEG/polysomnography had 71 channels recording physiological EEG activity from various cortical areas; seven channels recorded from the primary visual cortex. An equal number of 4-s phasic and tonic REM segments were selected. Patterns consistent with PGO waves were visually analyzed in both states in the primary visual cortex. Spectral analysis compared activity in the primary visual cortex with the remaining cortical areas. ResultsVisual inspection revealed an increase in sharply contoured theta waves (duration: 150–250 ms) in the primary visual cortex during phasic as compared to tonic REM sleep. Spectral analysis confirmed a 32% increase in mean absolute theta power during phasic versus tonic REM sleep (p corrected = 0.014). ConclusionNo classical PGO waves, but sharply contoured theta waves were found in the human primary visual cortex during phasic as opposed to tonic REM sleep. SignificanceThis research suggests that sharply contoured theta waves are the human correlate of PGO waves described in experimental animal models.

Hypothetical neurochemical mechanisms of paradoxical sleep deficiency in Alzheimer’s disease

Based on the known experimental data on the specific morphological and neurochemical changes in the neural circuits involved in the occurrence of paradoxical sleep (REM sleep) that are observed in Alzheimer’s disease (AD) and our analysis of the effects of neuromodulators on the functioning of these circuits we propose that REM sleep deficiency in AD is caused by the following mechanisms: (1) the activity of the lateral geniculate body and occipital cortex is not sufficient to generate the ponto-geniculo-occipital (PGO) waves that are specific for REM sleep due to lower activity of cholinergic cells of the pedunculopontine and laterodorsal tegmental nuclei (PPN and LDTN) and lower density of cholinergic receptors; (2) because of reduced activity of cholinergic neurons of the PPN and LDN on GABAergic interneurons projecting to noradrenergic and serotonergic cells, the activity of the latter cannot be completely inhibited, as should occur during REM sleep; (3) the concentration of melanin-concentrating hormone is not sufficient for sleep due to the decreased activity of cholinergic cells of the basal forebrain nucleus, which excite neurons that produce this hormone; and (4) the activity of histaminergic cells increases and the activity of neurons that release melanin-concentrating hormone decreases due to the increased orexin level. Our analysis shows that common use of drugs that increase the acetylcholine concentration in patients with AD may result in increased activity of orexinergic cells and this must prevent the occurrence of REM sleep. We hypothesize that microstimulation of PPN may improve the occurrence of REM sleep because it should decrease the activity of serotoninergic, noradrenergic, and histaminergic cells and promote the generation of PGO waves and hippocampal theta activity. This treatment may improve the conditions for memory consolidation in patients with AD. Such microstimulation should be applied at night according to a special protocol.

Towards a Functional Understanding of PGO Waves.

Ponto-Geniculo-Occipital (PGO) waves are biphasic field potentials identified in a range of mammalian species that are ubiquitous with sleep, but can also be identified in waking perception and eye movement. Their role in REM sleep and visual perception more broadly may constitute a promising avenue for further research, however what was once an active field of study has recently fallen into stasis. With the reality that invasive recordings performed on animals cannot be replicated in humans; while animals themselves cannot convey experience to the extent required to elucidate how PGO waves factor into awareness and behavior, innovative solutions are required if significant research outcomes are to ever be realized. Advances in non-invasive imaging technologies and sophistication in imaging methods now offer substantial scope to renew the study of the electrophysiological substrates of waking and dreaming perception. Among these, Magnetoencephalogram (MEG) stands out through its capacity to measure deep brain activations with high temporal resolution. With the current trend in sleep and dream research to produce translational findings of psychopathological and medical significance, in addition to the clear links that PGO wave generation sites share, pharmacologically, with receptors involved in expression of mental illness; there is a strong case to support scientific research into PGO waves and develop a functional understanding of their broader role in human perception.

El origen y las funciones de los sueños a partir de los potenciales PGO

El fenómeno del sueño y de los sueños es algo que siempre ha fascinado al hombre. Sin embargo, el estudio científico del sueño es relativamente reciente. En 1953, Aserinsky y Kleitman encontraron que el sueño de ondas lentas (SOL) es interrumpido periódicamente por episodios de actividad EEG rápida, que se acompañan de movimientos oculares rápidos (MORs), y denominaron a esta fase “sueño MOR”. Posteriormente, Dement y Kleitman, en 1957, descubrieron que estos movimientos oculares rápidos coinciden con la aparición de los sueños. Utilizando animales de experimentación se han estudiado los mecanismos subcorticales que subyacen al sueño MOR y se ha demostrado que éste depende de una actividad serotoninérgica de la vigilia, que promueve la formación de péptidos que ponen en marcha ciertas estructuras de la región pontina del tallo cerebral en donde se integran los mecanismos colinérgicos del sueño MOR. En la región pontina, a su vez, se generan potenciales monofásicos de alto voltaje (300-400 µV) que también pueden registrarse en el cuerpo geniculado lateral y en la corteza occipital, de allí el nombre de potenciales ponto-genículo-occipitales (PGO). Estos potenciales se propagan hacia el sistema oculomotor para provocar los MORs y posiblemente den origen a los fenómenos oníricos visuales. Además se ha demostrado que ciertas estructuras del sistema límbico, relacionadas con las emociones y la memoria, son activadas por dichos potenciales. Lo anterior sugiere que los potenciales PGO generan los componentes mnésicos y emocionales de los sueños. Quedan aún por determinarse varios aspectos sobre las funciones de estos potenciales, pero el conocimiento sobre el origen de los fenómenos cerebrales que generan los sueños ha tenido un gran avance a partir de su estudio. En el presente artículo se revisa la bibliografía concerniente a los trabajos realizados sobre los potenciales PGO y su aportación al conocimiento del origen y las funciones de los sueños.

Sleep, EEG and behavioral responses after systemic administration of gaboxadol in the laboratory cat

GABA and its receptors are widely distributed in sleep-wakefulness cycle (SWC) network structures, but action of extrasynaptic GABAA receptors in SWC mechanisms is not yet fully understood. The cat has been extensively used in SWC research, but to our knowledge there are no previous studies about the response of this species to the administration of gaboxadol, an extrasynaptic GABAA receptor agonist. The present study aims to characterize the effects of systemic gaboxadol administration on SWC states, EEG and behavior in laboratory cats. Four adults cats with electrodes for chronic sleep polygraphic recordings were used. Gaboxadol (doses 0.2–10.0 mg/kg) and saline were i.p. administered. Polygraphic-video recordings were obtained for 8 h post-injections. The lowest doses of gaboxadol (0.2, 0.5 and 1 mg/kg) produced little effect on SWC state proportions and polygraphic patterns were associated with normal postural behavioral and autonomic behaviors. Power spectra analyses showed EEG features of NREM sleep to be in the range of delta band values for spontaneous slow wave sleep (SWS). Administration of the largest dose (10 mg/kg) produced continuous slow waves in the EEG associated with odd postures, stuporous behavior, shallow breathing and markedly increased respiratory rate. Intermediate doses (2 and 5 mg/kg), did not have these undesirable effects and the cats alternated between different SWC states, with an enhancement of slow wave EEG activity duration. However, during the first 4 h of the recordings, the periods that could be scored as SWS on the basis of this slow wave EEG activity, were dissociated from behavior, as the animals remained with eyes open in a postural attitude typical of relaxed wakefulness or drowsiness. During these episodes the cats barely closed their eyes only when PGO waves appeared in the lateral geniculate nucleus recordings. In spite of the EEG/behavioral uncoupling in these experiments, power spectra analyses indicated a definite increased delta band during EEG slow wave activity. REM sleep episodes presented all the typical electrophysiological and behavioral characteristics and the proportions of the REM sleep remained fairly stable. Gaboxadol in cats produce SWC responses similar to that described in other species including man, but there is an unusual EEG/behavioral dissociation under gaboxadol that could be exploited to investigate extrasynaptic GABAA receptors not only in SWS but also in wakefulness. Supported by Grant BFU2009-06991 from MCyT, Spain

PGO activity after carbachol delivery in the oral and caudal pontine reticular nuclei: similarities and differences with spontaneous REM sleep in cats

Carbachol in the ventral part of the oral pontine reticular nucleus (vRPO) generates REM sleep with all its polygraphic characteristics. In contrast, cholinergic stimulation of the nearby rostral caudal pontine reticular nucleus (RPC) produces atonia and PGOs but with EEG sychronization. By quantifying PGO activity, this study further characterizes the effects of carbachol in these two pontine sites. Eight cats wearing electrodes for sleep polygraphic recordings were used; each had a guide-tube aimed at the vRPO or the RPC to administer carbachol (0.1 M, 20–30 nl) microinjections. Isolated PGO waves (Type I) and clusters with interspike intervals of ⩽330 ms of 2, 3 and ⩾4 PGOs (Type II, III and IV respectively) were quantified using one-minute epochs of 4 consecutive spontaneous REM sleep episodes (control) and then after carbachol in the vRPO and the RPC at the following times: when PGO activity was first detected (T0) and 10–15 (T10), 30–45 (T30) and 60–75 (T60) min later. Data from the different experimental conditions were compared with ANOVAs for repeated measures and the post hoc Fisher test. Atonia, desynchronized EEG and different types of PGOs occurred shortly after carbachol delivery in the vRPO, while a predominance of Type IV PGO clusters, numerous REMs, atonia and with a striking EEG theta synchronization occurred after carbachol in the RPC. The total number of PGOs and Type IV clusters were significantly higher in RPC experiments than in either spontaneous or vRPO Rem sleep in the T0 to T60 samples. These parameters were slightly lower than the spontaneous REM sleep values after vRPO carbachol delivery but, significant decreases only occurred immediately after the first appearance of PGO activity (T0). Also, the four PGO type proportions were fairly well preserved in carbachol vRPO experiments. In the RPC experiments, the proportions of the PGO patterns were different from spontaneous or carbachol vRPO Rem sleep (Types I and II significantly decreased and Type IV significantly increased). These results indicate that the vRPO is not only the prime region for the simultaneous appearance of tonic REM sleep signs (atonia and EEG desynchonization) but it can also to promote the cascade of events that establish the physiological pattern of PGO phasic activities. Cholinergic stimulation of the rostral RPC does not generate true REM sleep, but it is involved in the generation of atonia and of long trains of clustered PGO activity. Supported by Grant BFU2009-06991 from MCyT, Spain.

Generation of Ponto-Geniculo-Occipital (PGO) Waves as a Possible Cause of Impairments to Visual Perception during Microsleep

A hypothesis is proposed whereby one of the causes of impairments to visual perception in microsleep consists of the spontaneous generation of ponto-geniculo-occipital (PGO) waves. If the eyes are open during microsleep and PGO waves are generated, they can propagate to the thalamic projection nuclei. This degrades the conduction of visual information from the retina to the visual areas of the neocortex and the input structure of the basal ganglia – the striatum. Taking cognizance of our previously proposed mechanism of visual processing, which includes visual attention, the absence of striatal activation by visual stimuli makes it impossible for neurons in the superior colliculi, which conduct visual information to the dopaminergic structures, to be disinhibited via the basal ganglia. As a result, dopamine cannot be released in response to a visual stimulus, so attention to the stimulus is not triggered and its processing in all visual cortical areas is degraded. It should be possible to verify this hypothesis in experiments using an artificially evoked state of microsleep using non-invasive methods seeking correlates of the presence of PGO activity in the brain.

Conscious Modulation in Normal Sleep

The phenomenological relationship between consciousness and sleep are reviewed. Consciousness has a self- reflexive component, and while sleeping that is not working as in awakenings. The necessity of some change in narrow concepts of conscious as to be aware and self reflective as well of some aspects of Altered State of Consciousness are ex- plained. In fact, in rapid eye movements (REM) sleep is the sleep stage in which some perception of consciousness is found self-perception in REM sleep is a common phenomenon, but to be aware of that is called lucid dreams. Also sleep paralysis produce some activation of self-awareness. The lack of continuity between cortical areas in delta sleep stages could explain the loss of consciousness is such sleep stage, which support the idea of cortical continuity as a necessary condition for to achieve this integrative process. A ques- tion that emerges after update the knowledge about sleep and consciousness is what is the minimum degree of connec- tivity and activity of the central nervous system for to be conscious? New paradigms in neurosciences like connectome and enactivation, removes reductionist approaches to the main - body issue. Enactive approach could be used as a paradigm to understand cognitive activity in three neurophysiology stages. As a proposal, it can be figured out as follows: (A) In wakefulness, the enactive phenomenon has priority to start whatever action is necessary. A biofeedback to make corrections in order to improve the motor programs, mind theory or any other active strategies; (B) In REM sleep in which there is not external stimuli. Those are generated from the sensorial nuclei in the brainstem which generates internal electrical activity that follows sensorial pathways (i.e., PGO waves) with visual and emotional targets (i.e., occipital visual cortex and amygdale complex) and probably without enactivation, but inner generating stimulation so the brain cortex is activated mainly by brainstem without any anticipatory top-down events; and (C) In delta sleep, in which there are no enactivation and no sensorial inputs, but also there is no interconnectivity in the brain cortex, which is a necessary condition for consciousness and memory. New technical tools as functional magnetic resonance, trans-cranial magnetic stimulation, and magnetic electroencephalo- graphy have open new approaches for develop feasible hypotheses in this field.

Cholinergic modulation of GABAergic and glutamatergic transmission in the dorsal subcoeruleus: mechanisms for REM sleep control.

Dorsal subcoeruleus (SubCD) neurons are thought to promote PGO waves and to be modulated by cholinergic afferents during REM sleep. We examined the differential effect of the cholinergic agonist carbachol (CAR) on excitatory and inhibitory postsynaptic currents (PSCs), and investigated the effects of CAR on SubCD neurons during the developmental decrease in REM sleep. Whole-cell patch clamp recordings were conducted on brainstem slices of 7- to 20-day-old rats. CAR acted directly on 50% of SubCD neurons by inducing an inward current, via both nicotinic and muscarinic M1 receptors. CAR induced a potassium mediated outward current via activation of M2 muscarinic receptors in 43% of SubCD cells. Evoked stimulation established the presence of NMDA, AMPA, GABA, and glycinergic PSCs in the SubCD. CAR was found to decrease the amplitude of evoked EPSCs in 31 of 34 SubCD cells, but decreased the amplitude of evoked IPSCs in only 1 of 13 SubCD cells tested. Spontaneous EPSCs were decreased by CAR in 55% of cells recorded, while spontaneous IPSCs were increased in 27% of SubCD cells. These findings indicate that CAR exerts a predominantly inhibitory role on fast synaptic glutamatergic activity and a predominantly excitatory role on fast synaptic GABAergic/glycinergic activity in the SubCD. We hypothesize that during REM sleep, cholinergic "REM-on" neurons that project to the SubCD induce an excitation of inhibitory interneurons and inhibition of excitatory events leading to the production of coordinated activity in SubCD projection neurons. The coordination of these projection neurons may be essential for the production of REM sleep signs such as PGO waves.

Evidence of subthalamic PGO-like waves during REM sleep in humans: a deep brain polysomnographic study.

The aim of this study was to examine whether the subthalamic nucleus (STN) plays a role in the transmission of PGO-like waves during REM sleep in humans. Simultaneous recordings from deep brain electrodes to record local field potentials (LFPs), and standard polysomnography to ascertain sleep/wake states. Main Hospital, department of clinical neurophysiology sleep laboratory. 12 individuals with Parkinson's disease, with electrodes implanted in the STN; and, as a control for localization purposes, 4 cluster headache patients with electrodes implanted in the posterior hypothalamus. All subjects underwent functional neurosurgery for implantation of deep brain stimulation electrodes. Sharp, polarity-reversed LFPs were recorded within the STN during REM sleep in humans. These subthalamic PGO-like waves (2-3 Hz, 80-200 pV, and 300-500 msec) appeared during REM epochs as singlets or in clusters of 3-13 waves. During the pre-REM period, subthalamic PGO-like waves were temporally related to drops in the submental electromyogram and/or onset of muscular atonia. Clusters of PGO-like waves occurred typically before and during the bursts of rapid eye movements and were associated with an enhancement in fast (15-35 Hz) subthalamic oscillatory activity. Subthalamic PGO-like waves can be recorded during pre-REM and REM sleep in humans. Our data suggest that the STN may play an active role in an ascending activating network implicated in the transmission of PGO waves during REM sleep in humans.

Eye Movements and Abducens Motoneuron Behavior During Cholinergically Induced REM Sleep

The injection of cholinergic drugs in the pons has been largely used to induce REM sleep as a useful model to study different processes during this period. In the present study, microinjections of carbachol in the nucleus reticularis pontis oralis (NRPO) were performed to test the hypothesis that eye movements and the behavior of extraocular motoneurons during induced REM sleep do not differ from those during spontaneous REM sleep. Six female adult cats were prepared for chronic recording of eye movements (by means of the search-coil technique) and electroencephalography, electromyography, ponto-geniculo-occipital (PGO) waves at the lateral geniculate nucleus, and identified abducens motoneuron activities after microinjections of the cholinergic agonist carbachol into the NRPO. Unilateral microinjections (n = 13) of carbachol in the NRPO induced REM sleep-like periods in which the eyes performed a convergence and downward rotation interrupted by phasic complex rapid eye movements associated to PGO waves. During induced-REM sleep abducens motoneurons lost their tonic activity and eye position codification, but continued codifying eye velocity during the burst of eye movements. The present results show that eye movements and the underlying behavior of abducens motoneurons are very similar to those present during natural REM sleep. Thus, microinjection of carbachol seems to activate the structures responsible for the exclusive oculomotor behavior observed during REM sleep, validating this pharmacological model and enabling a more efficient exploration of phasic and tonic phenomena underlying eye movements during REM sleep.

Eye Movements and Abducens Motoneuron Behavior During Cholinergically Induced REM Sleep

The injection of cholinergic drugs in the pons has been largely used to induce REM sleep as a useful model to study different processes during this period. In the present study, microinjections of carbachol in the nucleus reticularis pontis oralis (NRPO) were performed to test the hypothesis that eye movements and the behavior of extraocular motoneurons during induced REM sleep do not differ from those during spontaneous REM sleep. Six female adult cats were prepared for chronic recording of eye movements (by means of the search-coil technique) and electroencephalography, electromyography, ponto-geniculo-occipital (PGO) waves at the lateral geniculate nucleus, and identified abducens motoneuron activities after microinjections of the cholinergic agonist carbachol into the NRPO. Unilateral microinjections (n = 13) of carbachol in the NRPO induced REM sleep-like periods in which the eyes performed a convergence and downward rotation interrupted by phasic complex rapid eye movements associated to PGO waves. During induced-REM sleep abducens motoneurons lost their tonic activity and eye position codification, but continued codifying eye velocity during the burst of eye movements. The present results show that eye movements and the underlying behavior of abducens motoneurons are very similar to those present during natural REM sleep. Thus, microinjection of carbachol seems to activate the structures responsible for the exclusive oculomotor behavior observed during REM sleep, validating this pharmacological model and enabling a more efficient exploration of phasic and tonic phenomena underlying eye movements during REM sleep.

Still Missing Some Significant Ingredients

Still Missing Some Significant Ingredients

Human brain activity time-locked to rapid eye movements during REM sleep

To identify the neural substrate of rapid eye movements (REMs) during REM sleep in humans, we conducted simultaneous functional magnetic resonance imaging (fMRI) and polysomnographic recording during REM sleep. Event-related fMRI analysis time-locked to the occurrence of REMs revealed that the pontine tegmentum, ventroposterior thalamus, primary visual cortex, putamen and limbic areas (the anterior cingulate, parahippocampal gyrus and amygdala) were activated in association with REMs. A control experiment during which subjects made self-paced saccades in total darkness showed no activation in the visual cortex. The REM-related activation of the primary visual cortex without visual input from the retina provides neural evidence for the existence of human ponto-geniculo-occipital waves (PGO waves) and a link between REMs and dreaming. Furthermore, the time-course analysis of blood oxygenation level-dependent responses indicated that the activation of the pontine tegmentum, ventroposterior thalamus and primary visual cortex started before the occurrence of REMs. On the other hand, the activation of the putamen and limbic areas accompanied REMs. The activation of the parahippocampal gyrus and amygdala simultaneously with REMs suggests that REMs and/or their generating mechanism are not merely an epiphenomenon of PGO waves, but may be linked to the triggering activation of these areas.

REM Illumination: Memory Consolidation

REM Illumination: Memory Consolidation

Inhibitory effect of state independent ponto-geniculo-occipital waves on seizure occurrence induced by local application of penicillin into the temporal lobe amygdala

Purpose In order to explore the possible inhibitory role of the phasic phenomena of REM sleep ponto-geniculo-occipital (PGO) waves over epilepsy, seizure activity produced by topic administration of Na-penicillin (PCN) has been analyzed during sustained PGO waves irrespective of current state. PGO waves were induced by the injection of carbachol in the peribrachial area. Methods The development of acute experimental epilepsy was compared among nine chronically implanted, adult, male cats, by means of polygraphic 23h recordings. Our protocol consisted of sets of 4 trials: carbachol; PCN; carbachol followed by PCN and finally PCN followed by carbachol. Each cat received one single set and all trials were carried out with a seven days interval, in order to compare the epileptic activity both in the presence of PGOs and without them. Results PGO waves 1) exert an inhibitory influence over number and duration of the Generalized Convulsive Seizures (GCSs) and 2) spike frequency; 3) increase the latency of GCSs; and 4) restores sleep alterations produced by experimental epilepsy. Conclusions PGO waves exhibit an inhibitory influence over seizures induced by PCN. These data support the hypothesis that this phasic phenomenon of REM sleep have a depressant effect on epilepsy, inhibit seizures and normalize sleep architecture changes induced by seizures. We suggest that one possible function of PGO activity is to protect the brain from intense changes in neuronal excitability; namely convulsive activity.