RESUMEN
Age-related decline in mobility and cognition are associated with cellular senescence and NAD + depletion in dogs and people. A combination of a novel NAD + precursor and senolytic, LY-D6/2, was examined in this randomized controlled trial. Seventy dogs with mild to moderate cognitive impairment were enrolled and allocated into placebo, low or full dose groups. Primary outcomes were change in cognitive impairment measured with the owner-reported Canine Cognitive Dysfunction Rating (CCDR) scale and change in activity measured with physical activity monitors. Fifty-nine dogs completed evaluations at the 3-month primary endpoint, and 51 reached the 6-month secondary endpoint. There was a significant difference in CCDR score across treatment groups from baseline to the primary endpoint (p = 0.02) with the largest decrease in the full dose group. No difference was detected between groups using in house cognitive testing. There were no significant differences between groups in changes in measured activity. The proportion of dogs that improved in frailty and owner-reported activity levels and happiness was higher in the full dose group than other groups, however this difference was not significant. Adverse events occurred equally across groups. All groups showed improvement in cognition, frailty, and activity suggesting placebo effect and benefits of trial participation. We conclude that LY-D6/2 improves owner-assessed cognitive function over a 3-month period and may have broader, but more subtle effects on frailty, activity and happiness as reported by owners.
Asunto(s)
Cognición , Disfunción Cognitiva , NAD , Animales , Perros , Masculino , Femenino , NAD/metabolismo , Enfermedades de los Perros/psicología , HumanosRESUMEN
Introduction: In humans, gait speed is a crucial component in geriatric evaluation since decreasing speed can be a harbinger of cognitive decline and dementia. Aging companion dogs can suffer from age-related mobility impairment, cognitive decline and dementia known as canine cognitive dysfunction syndrome. We hypothesized that there would be an association between gait speed and cognition in aging dogs. Methods: We measured gait speed on and off leash in 46 adult and 49 senior dogs. Cognitive performance in senior dogs was assessed by means of the Canine Dementia Scale and a battery of cognitive tests. Results: We demonstrated that dogs' food-motivated gait speed off leash is correlated with fractional lifespan and cognitive performance in dogs, particularly in the domains of attention and working memory. Discussion: Food-motivated gait speed off leash represents a relatively easy variable to measure in clinical settings. Moreover, it proves to be a more effective indicator of age-related deterioration and cognitive decline than gait speed on leash.
RESUMEN
PURPOSE: To determine the association between age and retinal full-field electroretinographic (ERG) measures in companion (pet) dogs, an important translational model species for human neurologic aging. METHODS: Healthy adult dogs with no significant ophthalmic abnormalities were included. Unilateral full-field light- and dark-adapted electroretinography was performed using a handheld device, with mydriasis and topical anaesthesia. Partial least squares effect screening analysis was performed to determine the effect of age, sex, body weight and use of anxiolytic medication on log-transformed ERG peak times and amplitudes; age and anxiolytic usage had significant effects on multiple ERG outcomes. Mixed model analysis was performed on data from dogs not receiving anxiolytic medications. RESULTS: In dogs not receiving anxiolytics, median age was 118 months (interquartile range 72-140 months, n = 77, 44 purebred, 33 mixed breed dogs). Age was significantly associated with prolonged peak times of a-waves (dark-adapted 3 and 10 cds/m2 flash p < 0.0001) and b-waves (cone flicker p = 0.03, dark-adapted 0.01 cds/m2 flash p = 0.001). Age was also significantly associated with reduced amplitudes of a-waves (dark-adapted 3 cds/m2 flash p < 0.0001, 10 cds/m2 flash p = 0.005) and b-waves (light-adapted 3 cds/m2 flash p < 0.0001, dark-adapted 0.01 cds/m2 flash p = 0.0004, 3 cds/m2 flash p < 0.0001, 10 cds/m2 flash p = 0.007) and flicker (light-adapted 30 Hz 3 cds/m2 p = 0.0004). Within the Golden Retriever breed, these trends were matched in a cross-sectional analysis of 6 individuals that received no anxiolytic medication. CONCLUSIONS: Aged companion dogs have slower and reduced amplitude responses in both rod- and cone-mediated ERG. Consideration of anxiolytic medication use should be made when conducting ERG studies in dogs.
Asunto(s)
Electrorretinografía , Mascotas , Adulto , Humanos , Animales , Perros , Anciano , Niño , Estudios Transversales , Adaptación a la Oscuridad , Estimulación LuminosaRESUMEN
Introduction: Sleep is fundamental for cognitive homeostasis, especially in senior populations since clearance of amyloid beta (key in the pathophysiology of Alzheimer's disease) occurs during sleep. Some electroencephalographic characteristics of sleep and wakefulness have been considered a hallmark of dementia. Owners of dogs with canine cognitive dysfunction syndrome (a canine analog to Alzheimer's disease) report that their dogs suffer from difficulty sleeping. The aim of this study was to quantify age-related changes in the sleep-wakefulness cycle macrostructure and electroencephalographic features in senior dogs and to correlate them with their cognitive performance. Methods: We performed polysomnographic recordings in 28 senior dogs during a 2 h afternoon nap. Percentage of time spent in wakefulness, drowsiness, NREM, and REM sleep, as well as latency to the three sleep states were calculated. Spectral power, coherence, and Lempel Ziv Complexity of the brain oscillations were estimated. Finally, cognitive performance was evaluated by means of the Canine Dementia Scale Questionnaire and a battery of cognitive tests. Correlations between age, cognitive performance and sleep-wakefulness cycle macrostructure and electroencephalographic features were calculated. Results: Dogs with higher dementia scores and with worse performance in a problem-solving task spent less time in NREM and REM sleep. Additionally, quantitative electroencephalographic analyses showed differences in dogs associated with age or cognitive performance, some of them reflecting shallower sleep in more affected dogs. Discussion: Polysomnographic recordings in dogs can detect sleep-wakefulness cycle changes associated with dementia. Further studies should evaluate polysomnography's potential clinical use to monitor the progression of canine cognitive dysfunction syndrome.
RESUMEN
Maintaining an active lifestyle is considered a hallmark of successful aging. Physical activity significantly reduces the risk of cognitive decline and Alzheimer's disease in humans. However, pain and lack of motivation are important barriers to exercise. Dogs are a remarkable model for translational studies in aging and cognition as they are prone to Canine Cognitive Dysfunction syndrome, which has many similarities with Alzheimer's disease. According to owner reports, changes in activity levels are characteristic of this syndrome, with decreased daytime activity, but also excessive pacing, especially at sleep time. We used physical activity monitors to record the activity of 27 senior dogs and evaluated the association between activity level and age, fractional lifespan, cognitive status measured by an owner questionnaire and cognitive tests. We also assessed the relationship between activity and joint/spinal pain, and the off/on leash gait speed ratio (a potential marker of gait speed reserve and motivation). We found that activity patterns in dogs are associated with fractional lifespan and working memory. Additionally, dogs with higher on/off leash gait speed are more active in the afternoon of weekdays. These results encourage future studies evaluating how physical activity can improve or delay cognitive impairment in senior dogs.
Asunto(s)
Enfermedad de Alzheimer , Disfunción Cognitiva , Humanos , Perros , Animales , Longevidad , Velocidad al Caminar , Marcha , Cognición , Envejecimiento/psicología , DolorRESUMEN
While much work has been done in the field of canine olfaction, there has been little exploration of hyposmia or anosmia. This is partly due to difficulties in reducing confounds like training history and environmental distraction. The current study describes a novel olfaction test using spontaneous search behavior in dogs to find a hidden food treat in a three-choice task with both light-phase and dark-phase conditions. The study was performed in 18 adult control dogs, 18 senior/geriatric dogs enrolled in a longitudinal aging study, and a single dog with severe nasal pathology. In the senior/geriatric and control groups, dogs performed with higher accuracy (p < 0.0001) and were less likely to show biased selection strategy (p < 0.01) in the dark-phase than light-phase. While senior/geriatric dogs performed above chance, they had lower accuracy in the dark-phase compared to controls (p = 0.036). Dogs who scored higher on an owner questionnaire of cognitive decline showed a positive correlation with performance in the dark-phase; performance on additional cognitive tests did not correlate with performance in the dark-phase. This task can be used to quantify canine olfaction using clearly defined endpoints and spontaneous behaviors thus making it feasible to compare between and within groups of pet dogs.
Asunto(s)
Alimentos , Olfato , Perros , Animales , Envejecimiento , Pruebas NeuropsicológicasRESUMEN
Nasal respiration influences brain dynamics by phase-entraining neural oscillations at the same frequency as the breathing rate and by phase-modulating the activity of faster gamma rhythms. Despite being widely reported, we still do not understand the functional roles of respiration-entrained oscillations. A common hypothesis is that these rhythms aid long-range communication and provide a privileged window for synchronization. Here we tested this hypothesis by analyzing electrocorticographic (ECoG) recordings in mice, rats, and cats during the different sleep-wake states. We found that the respiration phase modulates the amplitude of cortical gamma oscillations in the three species, although the modulated gamma frequency bands differed with faster oscillations (90-130 Hz) in mice, intermediate frequencies (60-100 Hz) in rats, and slower activity (30-60 Hz) in cats. In addition, our results also show that respiration modulates olfactory bulb-frontal cortex synchronization in the gamma range, in which each breathing cycle evokes (following a delay) a transient time window of increased gamma synchrony. Long-range gamma synchrony modulation occurs during quiet and active wake states but decreases during sleep. Thus, our results suggest that respiration-entrained brain rhythms orchestrate communication in awake mammals.
Asunto(s)
Ritmo Gamma , Respiración , Ratas , Ratones , Gatos , Animales , Encéfalo , Bulbo Olfatorio , Sueño , Electroencefalografía , MamíferosRESUMEN
Aging is associated with impairment in postural control in humans. While dogs are a powerful model for the study of aging, the associations between age and postural control in this species have not yet been elucidated. The aims of this work were to establish a reliable protocol to measure center of pressure excursions in standing dogs and to determine age-related changes in postural sway. Data were obtained from 40 healthy adult dogs (Group A) and 28 senior dogs (Group B) during seven trials (within one session of data collection) of quiet standing on a pressure sensitive walkway system. Velocity, acceleration, root mean square, 95% ellipse area, range and frequency revolve were recorded as measures of postural sway. In Group A, reliability was assessed with intraclass correlation, and the effect of morphometric variables was evaluated using linear regression. By means of stepwise linear regression we determined that root mean square overall and acceleration in the craniocaudal direction were the best variables able to discriminate between Group A and Group B. The relationship between these two center-of-pressure (COP) measures and the dogs' fractional lifespan was examined in both groups and the role of pain and proprioceptive deficits was evaluated in Group B. All measures except for frequency revolve showed good to excellent reliability. Weight, height and length were correlated with most of the measures. Fractional lifespan impacted postural control in Group B but not Group A. Joint pain and its interaction with proprioceptive deficits influence postural sway especially in the acceleration in the craniocaudal direction, while fractional lifespan was most important in the overall COP displacement. In conclusion, our study found that pressure sensitive walkway systems are a reliable tool to evaluate postural sway in dogs; and that postural sway is affected by morphometric parameters and increases with age and joint pain.
Asunto(s)
Envejecimiento , Equilibrio Postural , Aceleración , Animales , Artralgia , Perros , Reproducibilidad de los ResultadosRESUMEN
Canine cognitive dysfunction (CCD) is a highly prevalent neurodegenerative disease considered the canine analog of early Alzheimer's disease (AD). Unfortunately, CCD cannot be cured. However, early therapeutic interventions can slow the progression of cognitive decline and improve quality of life of the patients; therefore, early diagnosis is ideal. In humans, electroencephalogram (EEG) findings specific to AD have been described, and some of them have successfully detect early stages of the disease. In this study we characterized the EEG correlates of CCD, and we compared them with the EEGs of healthy aging dogs and dogs at risk of developing CCD. EEG recordings were performed in 25 senior dogs during wakefulness. Dogs were categorized in normal, at risk of CCD or with CCD according to their score in the Rofina questionnaire. We demonstrated that, quantitative EEG can detect differences between normal dogs and dogs with CCD. Dogs with CCD experience a reduction in beta and gamma interhemispheric coherence, and higher Joint Lempel Ziv complexity. Dogs at risk of developing CCD, had higher alpha power and interhemispheric coherence, making these features potential markers of early stages of the disease. These results demonstrate that quantitative EEG analysis could aid the diagnosis of CCD, and reinforce the CCD as a translational model of early AD.
Asunto(s)
Trastornos del Conocimiento , Disfunción Cognitiva , Enfermedades de los Perros , Enfermedades Neurodegenerativas , Animales , Trastornos del Conocimiento/diagnóstico , Trastornos del Conocimiento/psicología , Disfunción Cognitiva/diagnóstico , Enfermedades de los Perros/diagnóstico , Perros , Electroencefalografía/veterinaria , Humanos , Enfermedades Neurodegenerativas/veterinaria , Calidad de VidaRESUMEN
Urethane is a general anaesthetic widely used in animal research. The state of urethane anaesthesia is unique because it alternates between macroscopically distinct electrographic states: a slow-wave state that resembles non-rapid eye movement (NREM) sleep and an activated state with features of both REM sleep and wakefulness. Although it is assumed that urethane produces unconsciousness, this has been questioned because of states of cortical activation during drug exposure. Furthermore, the similarities and differences between urethane anaesthesia and physiological sleep are still unclear. In this study, we recorded the electroencephalogram (EEG) and electromyogram in chronically prepared rats during natural sleep-wake states and during urethane anaesthesia. We subsequently analysed the power, coherence, directed connectivity and complexity of brain oscillations and found that EEG under urethane anaesthesia has clear signatures of unconsciousness, with similarities to other general anaesthetics. In addition, the EEG profile under urethane is different in comparison with natural sleep states. These results suggest that consciousness is disrupted during urethane. Furthermore, despite similarities that have led others to conclude that urethane is a model of sleep, the electrocortical traits of depressed and activated states during urethane anaesthesia differ from physiological sleep states.
RESUMEN
Recently, the sleep-wake states have been analysed using novel complexity measures, complementing the classical analysis of EEGs by frequency bands. This new approach consistently shows a decrease in EEG's complexity during slow-wave sleep, yet it is unclear how cortical oscillations shape these complexity variations. In this work, we analyse how the frequency content of brain signals affects the complexity estimates in freely moving rats. We find that the low-frequency spectrum - including the Delta, Theta, and Sigma frequency bands - drives the complexity changes during the sleep-wake states. This happens because low-frequency oscillations emerge from neuronal population patterns, as we show by recovering the complexity variations during the sleep-wake cycle from micro, meso, and macroscopic recordings. Moreover, we find that the lower frequencies reveal synchronisation patterns across the neocortex, such as a sensory-motor decoupling that happens during REM sleep. Overall, our works shows that EEG's low frequencies are critical in shaping the sleep-wake states' complexity across cortical scales.
Asunto(s)
Neocórtex , Vigilia , Animales , Electroencefalografía , Ratas , Sueño/fisiología , Sueño REM/fisiología , Vigilia/fisiologíaRESUMEN
Introduction: The aim of this study was to evaluate the engagement of aging dogs with a cognitively challenging and potentially frustrating task (the impossible task). Based on previous observations, we predicted that dogs showing signs of cognitive impairment in other cognitive tests and owner-completed questionnaires would show reduced engagement with the task. Methods: In this task, dogs were shown a piece of food in a clear container that they could not open; time spent interacting with the container and the experimenter was measured. While the impossible task has not been used as a measure of frustration, the parameters of the test design creates a potential frustrate state, making this assessment appropriate. Thirty-two dogs enrolled in a longitudinal aging study participated in the study. Owners were asked to complete two cognitive dysfunction screening questionnaires (Canine Dementia Scale [CADES] and Canine Cognitive Dysfunction Rating Scale [CCDR]) as well a questionnaire assessing general frustration. Dogs participated in multiple measures of cognitive function as well the impossible task. Results: Latency to disengage from the impossible task was faster for dogs with higher total (more impaired) CADES (p = 0.02) and total CCDR (p = 0.04) scores. Latency to disengage also correlated with decreased performance in cognitive tests observing social cues (p = 0.01), working memory (p ≤ 0.001), spatial reasoning and reversal learning (p = 0.02), and sustained attention (p = 0.02). Discussion: The high correlation with several cognitive measures and the ease of administration of this test makes it a useful tool in evaluating canine cognitive dysfunction syndrome, however it is unclear if increased frustration or other cognitive processes are contributing to the observed changes.
RESUMEN
Ibogaine is a psychedelic alkaloid that has attracted large scientific interest because of its antiaddictive properties in observational studies in humans as well as in animal models. Its subjective effect has been described as intense, vivid dream-like experiences occurring while awake; hence, ibogaine is often referred to as an oneirogenic psychedelic. While this unique dream-like profile has been hypothesized to aid the antiaddictive effects, the electrophysiological signatures of this psychedelic state remain unknown. We previously showed in rats that ibogaine promotes a waking state with abnormal motor behavior along with a decrease in NREM and REM sleep. Here, we performed an in-depth analysis of the intracranial electroencephalogram during "ibogaine wakefulness". We found that ibogaine induces gamma oscillations that, despite having larger power than control levels, are less coherent and less complex. Further analysis revealed that this profile of gamma activity compares to that of natural REM sleep. Thus, our results provide novel biological evidence for the association between the psychedelic state and REM sleep, contributing to the understanding of the brain mechanisms associated with the oneirogenic psychedelic effect of ibogaine.
RESUMEN
Clinical and experimental data from the last nine decades indicate that the preoptic area of the hypothalamus is a critical node in a brain network that controls sleep onset and homeostasis. By contrast, we recently reported that a group of glutamatergic neurons in the lateral and medial preoptic area increases wakefulness, challenging the long-standing notion in sleep neurobiology that the preoptic area is exclusively somnogenic. However, the precise role of these subcortical neurons in the control of behavioral state transitions and cortical dynamics remains unknown. Therefore, in this study, we used conditional expression of excitatory hM3Dq receptors in these preoptic glutamatergic (Vglut2+) neurons and show that their activation initiates wakefulness, decreases non-rapid eye movement (NREM) sleep, and causes a persistent suppression of rapid eye movement (REM) sleep. We also demonstrate, for the first time, that activation of these preoptic glutamatergic neurons causes a high degree of NREM sleep fragmentation, promotes state instability with frequent arousals from sleep, decreases body temperature, and shifts cortical dynamics (including oscillations, connectivity, and complexity) to a more wake-like state. We conclude that a subset of preoptic glutamatergic neurons can initiate, but not maintain, arousals from sleep, and their inactivation may be required for NREM stability and REM sleep generation. Further, these data provide novel empirical evidence supporting the hypothesis that the preoptic area causally contributes to the regulation of both sleep and wakefulness.SIGNIFICANCE STATEMENT Historically, the preoptic area of the hypothalamus has been considered a key site for sleep generation. However, emerging modeling and empirical data suggest that this region might play a dual role in sleep-wake control. We demonstrate that chemogenetic stimulation of preoptic glutamatergic neurons produces brief arousals that fragment sleep, persistently suppresses REM sleep, causes hypothermia, and shifts EEG patterns toward a "lighter" NREM sleep state. We propose that preoptic glutamatergic neurons can initiate, but not maintain, arousal from sleep and gate REM sleep generation, possibly to block REM-like intrusions during NREM-to-wake transitions. In contrast to the long-standing notion in sleep neurobiology that the preoptic area is exclusively somnogenic, we provide further evidence that preoptic neurons also generate wakefulness.
Asunto(s)
Ácido Glutámico/metabolismo , Hipotálamo/fisiología , Neuronas/fisiología , Sueño REM , Vigilia , Animales , Ondas Encefálicas , Hipotálamo/citología , Masculino , Ratones , Ratones Endogámicos C57BL , Neuronas/metabolismo , Proteína 2 de Transporte Vesicular de Glutamato/genética , Proteína 2 de Transporte Vesicular de Glutamato/metabolismoRESUMEN
Sleep is a fundamental process in mammals, including domestic dogs. Disturbances in sleep affect physiological functions like cognitive and physical performance, immune response, pain sensation and increase the risk of diseases. In dogs, sleep can be affected by several conditions, with narcolepsy, REM sleep behavior disorder and sleep breathing disorders being the most frequent causes. Furthermore, sleep disturbances can be a symptom of other primary diseases where they can contribute to the worsening of clinical signs. This review describes reciprocally interacting sleep and wakefulness promoting systems and how their dysfunction can explain the pathophysiological mechanisms of sleep disorders. Additionally, this work discusses the clinical characteristics, diagnostic tools and available treatments for these disorders while highlighting areas in where further studies are needed so as to improve their treatment and prevention.
Asunto(s)
Enfermedades de los Perros , Narcolepsia , Trastorno de la Conducta del Sueño REM , Trastornos del Sueño-Vigilia , Animales , Perros , Narcolepsia/veterinaria , Trastorno de la Conducta del Sueño REM/veterinaria , Sueño , Trastornos del Sueño-Vigilia/veterinaria , VigiliaRESUMEN
Despite the fact that medical properties of Cannabis have been recognized for more than 5000 years, the use of Cannabis for medical purposes have recently reemerged and became more accessible. Cannabis is usually employed as a self-medication for the treatment of insomnia disorder. However, the effects of Cannabis on sleep depend on multiple factors such as metabolomic composition of the plant, dosage and route of administration. In the present chapter, we reviewed the main effect Cannabis on sleep. We focused on the effect of "crude or whole plant" Cannabis consumption (i.e., smoked, oral or vaporized) both in humans and experimental animal models.The data reviewed establish that Cannabis modifies sleep. Furthermore, a recent experimental study in animals suggests that vaporization (which is a recommended route for medical purposes) of Cannabis with high THC and negligible CBD, promotes NREM sleep. However, it is imperative to perform new clinical studies in order to confirm if the administration of Cannabis could be a beneficial therapy for the treatment of sleep disorders.
Asunto(s)
Cannabis , Fumar Marihuana , Analgésicos , Animales , Humanos , Sueño , VolatilizaciónRESUMEN
Melanin concentrating hormone (MCH) is a sleep-promoting neuromodulator synthesized by neurons located in the postero-lateral hypothalamus and incerto-hypothalamic area. MCHergic neurons have widespread projections including the serotonergic dorsal (DR) and median (MnR) raphe nuclei, both involved in the control of wakefulness and sleep. In the present study, we explored in rats the presence of the MCH receptor type 1 (MCHR-1) in serotonergic neurons of the MnR by double immunofluorescence. Additionally, we analyzed the effect on sleep of MCH microinjections into the MnR. We found that MCHR-1 protein was present in MnR serotonergic and non-serotonergic neurons. In this respect, the receptor was localized in the primary cilia of these neurons. Compared with saline, microinjections of MCH into the MnR induced a dose-related increase in REM sleep time, which was related to a rise in the number of REM sleep episodes, associated with a reduction in the time spent in W. No signiï¬cant changes were observed in non-REM (NREM) sleep time. Our data strongly suggest that MCH projections towards the MnR, acting through the MCHR-1 located in the primary cilia, promote REM sleep.
RESUMEN
The sleep-wake cycle is constituted by three behavioral states: wakefulness (W), non-REM (NREM) and REM sleep. These states are associated with drastic changes in cognitive capacities, mostly determined by the function of the thalamo-cortical system, whose activity can be examined by means of intra-cranial electroencephalogram (iEEG). With the purpose to study in depth the basal activity of the iEEG in adult rats, we analyzed the spectral power and coherence of the iEEG during W and sleep in the paleocortex (olfactory bulb), and in neocortical areas. We also analyzed the laterality of the signals, as well as the influence of the light and dark phases. We found that the iEEG power and coherence of the whole spectrum were largely affected by behavioral states and highly dependent on the cortical areas recorded. We also determined that there are night/day differences in power and coherence during sleep, but not in W. Finally, we observed that, during REM sleep, intra-hemispheric coherence differs between right and left hemispheres. We conclude that the iEEG dynamics are highly dependent on the cortical area and behavioral states. Moreover, there are light/dark phases disparities in the iEEG during sleep, and intra-hemispheric connectivity differs between both hemispheres during REM sleep.
RESUMEN
The theory of communication through coherence (CTC) posits the synchronization of brain oscillations as a key mechanism for information sharing and perceptual binding. In a parallel literature, hippocampal theta activity (4-10â¯Hz) has been shown to modulate the appearance of neocortical fast gamma oscillations (100-150â¯Hz), a phenomenon known as cross-frequency coupling (CFC). Even though CFC has also been previously associated with information routing, it remains to be determined whether it directly relates to CTC. In particular, for the theta-fast gamma example at hand, a critical question is to know if the phase of the theta cycle influences gamma synchronization across the neocortex. To answer this question, we combined CFC (modulation index) and CTC (phase-locking value) metrics in order to detect the modulation of the cross-regional high-frequency synchronization by the phase of slower oscillations. Upon applying this method, we found that the inter-hemispheric synchronization of neocortical fast gamma during REM sleep depends on the instantaneous phase of the theta rhythm. These results show that CFC is likely to aid long-range information transfer by facilitating the synchronization of faster rhythms, thus consistent with classical CTC views.
Asunto(s)
Neocórtex , Ritmo Teta , Comunicación , Hipocampo , Sueño REMRESUMEN
The precise mechanism of general anesthesia remains unclear. In the last two decades, there has been considerable focus on the hypothesis that anesthetics co-opt the neural mechanisms regulating sleep. This hypothesis is supported by ample correlative evidence at the level of sleep-promoting nuclei, but causal investigations of potent inhaled anesthetics have not been conducted. Here, we tested the hypothesis that chemogenetic activation of discrete neuronal subpopulations within the median preoptic nucleus (MnPO) and ventrolateral preoptic nucleus (VLPO) of the hypothalamus would modulate sleep/wake states and alter the time to loss and resumption of consciousness associated with isoflurane, a potent halogenated ether in common clinical use. We show that activating MnPO/VLPO GABAergic or glutamatergic neurons does not alter anesthetic induction or recovery time. However, activation of these neuronal subpopulations did alter sleep-wake architecture. Notably, we report the novel finding that stimulation of VLPO glutamatergic neurons causes a strong increase in wakefulness. We conclude that activation of preoptic GABAergic or glutamatergic neurons that increase sleep or wakefulness does not substantively influence anesthetic state transitions. These data indicate that the correlative evidence for a mechanistic overlap of sleep and anesthesia at the level of an individual nucleus might not necessarily have strong causal significance.