Websciences International

Los Angeles, CA, United States

Websciences International

Los Angeles, CA, United States
SEARCH FILTERS
Time filter
Source Type

Torterolo P.,University of the Republic of Uruguay | Sampogna S.,WebSciences International | Chase M.H.,WebSciences International | Chase M.H.,University of California at Los Angeles
Neuroscience | Year: 2011

The principal site that generates both rapid eye movement (REM) sleep and wakefulness is located in the mesopontine reticular formation, whereas non-rapid eye movement (NREM) sleep is primarily dependent upon the functioning of neurons that are located in the preoptic region of the hypothalamus. In the present study, we were interested in determining whether the occurrence of NREM might also depend on the activity of mesopontine structures, as has been shown for wakefulness and REM sleep. Adult cats were maintained in one of the following states: quiet wakefulness (QW), alert wakefulness (AW), NREM, or REM sleep induced by microinjections of carbachol into the nucleus pontis oralis (REM-carbachol). Subsequently, they were euthanized and single-labeling immunohistochemical studies were undertaken to determine state-dependent patterns of neuronal activity in the brainstem based upon the expression of the protein Fos. In addition, double-labeling immunohistochemical studies were carried out to detect neurons that expressed Fos as well as choline acetyltransferase, tyrosine hydroxylase, or GABA. During NREM, only a few Fos-immunoreactive cells were present in different regions of the brainstem; however, a discrete cluster of Fos+ neurons was observed in the caudolateral parabrachial region (CLPB). The number of Fos+ neurons in the CLPB during NREM was significantly greater (67.9±10.9, P<0.0001) compared with QW (8.0±6.7), AW (5.2±4.2), or REM-carbachol (8.0±4.7). In addition, there was a positive correlation (R=0.93) between the time the animals spent in NREM and the number of Fos+ neurons in the CLPB. Fos-immunoreactive neurons in the CLPB were neither cholinergic nor catecholaminergic; however, about 50% of these neurons were GABAergic. We conclude that a group of GABAergic and unidentified neurons in the CLPB are active during NREM and likely involved in the control of this behavioral state. These data open new avenues for the study of NREM, as well as for the explorations of interactions between these neurons that are activated during NREM and cells of the adjacent pontine tegmentum that are involved in the generation of REM sleep. © 2011 IBRO.


Yamuy J.,WebSciences International | Fung S.J.,WebSciences International | Xi M.,WebSciences International | Chase M.H.,WebSciences International
Experimental Neurology | Year: 2010

Neurons in the lateral hypothalamus (LH) that synthesize hypocretins (Hcrt-1 and Hcrt-2) are active during wakefulness and excite lumbar motoneurons. Because hypocretinergic cells also discharge during phasic periods of rapid eye movement (REM) sleep, we sought to examine their action on the activity of motoneurons during this state. Accordingly, cat lumbar motoneurons were intracellularly recorded, under α-chloralose anesthesia, prior to (control) and during the carbachol-induced REM sleep-like atonia (REMc). During control conditions, LH stimulation induced excitatory postsynaptic potentials (composite EPSP) in motoneurons. In contrast, during REMc, identical LH stimulation induced inhibitory PSPs in motoneurons. We then tested the effects of LH stimulation on motoneuron responses following the stimulation of the nucleus reticularis gigantocellularis (NRGc) which is part of a brainstem-spinal cord system that controls motoneuron excitability in a state-dependent manner. LH stimulation facilitated NRGc stimulation-induced composite EPSP during control conditions whereas it enhanced NRGc stimulation-induced IPSPs during REMc. These intriguing data indicate that the LH exerts a state-dependent control of motor activity. As a first step to understand these results, we examined whether hypocretinergic synaptic mechanisms in the spinal cord were state dependent. We found that the juxtacellular application of Hcrt-1 induced motoneuron excitation during control conditions whereas motoneuron inhibition was enhanced during REMc. These data indicate that the hypocretinergic system acts on motoneurons in a state-dependent manner via spinal synaptic mechanisms. Thus, deficits in Hcrt-1 may cause the coexistence of incongruous motor signs in cataplectic patients, such as motor suppression during wakefulness and movement disorders during REM sleep. © 2009 Elsevier Inc. All rights reserved.


Benedetto L.,University of the Republic of Uruguay | Chase M.H.,WebSciences International | Chase M.H.,University of California at Los Angeles | Torterolo P.,University of the Republic of Uruguay
Behavioural Brain Research | Year: 2012

GABAergic mechanisms in the preoptic region of the hypothalamus (POA) have been implicated in the generation and maintenance of NREM (quiet) sleep. We recently reported that neurons in the median peptic nucleus (MnPN) in the POA of the cat are selectively activated during NREM sleep. In the present study, we explored the hypothesis that NREM sleep is controlled by GABAergic mechanisms within the MnPN. Consequently, adult cats were utilized to determine GABA immunorreactivity within the MnPN and to examine the effects on sleep of the microinjection of a GABA A agonist (muscimol) and a GABA A antagonist (bicuculline) into this area.GABAergic neurons were present throughout the MnPN. Compared with control microinjections, after the application of muscimol, the time spent in NREM sleep (59.8. ±. 7.5. min) and REM sleep (6.9. ±. 4.7. min) decreased compared with control microinjections (103.8. ±. 5.2 and 20.2. ±. 4.3. min, respectively; . P<. 0.005). In contrast, bicuculline microinjections increased only NREM sleep time (103.0. ±. 23.0 vs 77.7. ±. 23.7. min; . P<. 0.05).These results demonstrate that GABAergic processes within the MnPN are involved in the generation and maintenance of sleep, especially NREM sleep. © 2012 Elsevier B.V.


Fung S.J.,VA Greater Los Angeles Healthcare System | Xi M.,VA Greater Los Angeles Healthcare System | Zhang J.,VA Greater Los Angeles Healthcare System | Sampogna S.,WebSciences International | And 2 more authors.
Experimental Neurology | Year: 2012

Obstructive sleep apnea (OSA) results in the degeneration of neurons in the hippocampus that eventuates in neurocognitive deficits. We were therefore interested in determining the effects of apnea on monosynaptic excitatory processes in a hippocampal pathway (cornu ammonis 3-cornu ammonis 1, CA3-CA1) that has been shown to mediate the processing of cognitive information. In addition, to substantiate an anatomical basis for the cognitive dysfunction that occurs in OSA patients, we examined the effects of apnea with respect to neurodegenerative changes (apoptosis) in the same hippocampal pathway.In order to determine the effects of apnea, an automated system for the generation and analysis of single and recurrent periods of apnea was developed. Utilizing this system, the field excitatory postsynaptic potential (fEPSP) generated by pyramidal neurons in the CA1 region of the hippocampus was monitored in α-chloralose anesthetized rats following stimulation of glutamatergic afferents in the CA3 region. A stimulus-response (input-output) curve for CA3-CA1 synaptic activity was determined. In addition, a paired-pulse paradigm was employed to evaluate, electrophysiologically, the presynaptic release of glutamate. Changes in the synaptic efficacy were assessed following single episodes of apnea induced by ventilatory arrest (60 to 80. s duration, mean = 72 s; mean oxygen desaturation was 53% of normoxia level).Apnea resulted in a significant potentiation of the amplitude (mean = 126%) and slope (mean = 117%) of the baseline CA1 fEPSP. This increase in the fEPSP was accompanied by a significant decrease in the amplitude (71%) and slope (81%) of normalized paired-pulse facilitation (PPF) ratios. Since the potentiation of the fEPSP is inversely proportional to changes in PPF ratio, the potentiated fEPSP accompanied by the reduced PPF reveals that apnea produces an abnormal increase in the preterminal release of glutamate that results in the over-activation (and calcium overloading) of hippocampal CA1 neurons. Thus, we conclude that individual episodes of apnea result in the development of excitotoxic processes in the hippocampal CA3-CA1 pathway that is critically involved in the processing of cognitive information. Morphologically, the deleterious effect of recurrent apnea was substantiated by the finding of apoptosis in CA1 neurons of apneic (but not normoxic) animals. © 2012 Elsevier Inc.


Castro S.,University of the Republic of Uruguay | Falconi A.,University of the Republic of Uruguay | Chase M.H.,WebSciences International | Chase M.H.,University of California at Los Angeles | Torterolo P.,University of the Republic of Uruguay
European Journal of Neuroscience | Year: 2013

During cognitive processes there are extensive interactions between various regions of the cerebral cortex. Oscillations in the gamma frequency band (≈40Hz) of the electroencephalogram (EEG) are involved in the binding of spatially separated but temporally correlated neural events, which results in a unified perceptual experience. The extent of these interactions can be examined by means of a mathematical algorithm called 'coherence', which reflects the 'strength' of functional interactions between cortical areas. The present study was conducted to analyse EEG coherence in the gamma frequency band of the cat during alert wakefulness (AW), quiet wakefulness (QW), non-rapid eye movement (NREM) sleep and rapid eye movement (REM) sleep. Cats were implanted with electrodes in the frontal, parietal and occipital cortices to monitor EEG activity. Coherence values within the gamma frequency (30-100Hz) from pairs of EEG recordings were analysed. A large increase in coherence occurred between all cortical regions in the 30-45Hz frequency band during AW compared with the other behavioral states. As the animal transitioned from AW to QW and from QW to NREM sleep, coherence decreased to a moderate level. Remarkably, there was practically no EEG coherence in the entire gamma band spectrum (30-100Hz) during REM sleep. We conclude that functional interactions between cortical areas are radically different during sleep compared with wakefulness. The virtual absence of gamma frequency coherence during REM sleep may underlie the unique cognitive processing that occurs during dreams, which is principally a REM sleep-related phenomenon. © 2013 Federation of European Neuroscience Societies and Blackwell Publishing Ltd.


Torterolo P.,University of the Republic of Uruguay | Sampogna S.,WebSciences International | Chase M.H.,WebSciences International | Chase M.H.,University of California at Los Angeles
Brain Research | Year: 2013

Within the postero-lateral hypothalamus neurons that utilize hypocretin or melanin-concentrating hormone (MCH) as neuromodulators are co-distributed. These neurons have been involved in the control of behavioral states, and a deficit in the hypocretinergic system is the pathogenic basis of narcolepsy with cataplexy. In this report, utilizing immunohistochemistry and retrograde tracing techniques, we examined the hypocretinergic innervation of the nucleus pontis oralis (NPO), which is the executive site that is responsible for the generation of REM sleep in the cat. The retrograde tracer cholera toxin subunit b (CTb) was administered in pontine regions where carbachol microinjections induced REM sleep. Utilizing immunohistochemical techniques, we found that approximately 1% of hypocretinergic neurons in the tuberal area of the hypothalamus project to the NPO. In addition, approximately 6% of all CTb+ neurons in this region were hypocretinergic. The hypocretinergic innervation of the NPO was also compared with the innervation of the same site by MCH-containing neurons. More than three times as many MCHergic neurons were found to project to the NPO compared with hypocretinergic cells; both neuronal types exhibited bilateral projections. We also identified a group of non-hypocretinergic non-MCHergic neuronal group of neurons that were intermingled with both hypocretinergic and MCHergic neurons that also projected to this same brainstem region. These neurons were grater in number that either hypocretin or MCH-containing neurons; their soma size was also smaller and their projections were mainly ipsilateral. The present anatomical data suggest that hypocretinergic, MCHergic and an unidentified companion group of neurons of the postero-lateral hypothalamus participate in the regulation of the neuronal activity of NPO neurons, and therefore, are likely to participate in the control of wakefulness and REM sleep. © 2012 Elsevier B.V. All rights reserved.


Torterolo P.,University of the Republic of Uruguay | Chase M.H.,WebSciences International | Chase M.H.,University of California at Los Angeles
Sleep Science | Year: 2014

In 1998, a group of phenotypically distinct neurons were discovered in the postero-lateral hypothalamus which contained the neuropeptides hypocretin 1 and hypocretin 2 (also called orexin A and orexin B), which are excitatory neuromodulators. Hypocretinergic neurons project throughout the central nervous system and have been involved in the generation and maintenance of wakefulness. The sleep disorder narcolepsy, characterized by hypersomnia and cataplexy, is produced by degeneration of these neurons. The hypocretinergic neurons are active during wakefulness in conjunction with the presence of motor activity that occurs during survival-related behaviors. These neurons decrease their firing rate during non-REM sleep; however there is still controversy upon the activity and role of these neurons during REM sleep. Hence, in the present report we conducted a critical review of the literature of the hypocretinergic system during REM sleep, and hypothesize a possible role of this system in the generation of REM sleep. © 2014 Published by Elsevier B.V. on behalf of Brazilian Association of Sleep.


Castro S.,University of the Republic of Uruguay | Cavelli M.,University of the Republic of Uruguay | Vollono P.,University of the Republic of Uruguay | Chase M.H.,WebSciences International | And 3 more authors.
Neuroscience Letters | Year: 2014

Oscillations in the gamma frequency band (mainly ≈40. Hz) of the electroencephalogram (EEG) have been involved in the binding of spatially separated but temporally correlated neural events that result in a unified perceptual experience. The extent of these interactions can be examined by means of a mathematical algorithm called "coherence", which reflects the "strength" of functional interactions between cortical areas. As a continuation of a previous study of our group, the present study was conducted to analyze the inter-hemispheric coherence of the EEG gamma frequency band in the cat during alert wakefulness (AW), quiet wakefulness (QW), non-REM (NREM) sleep and REM sleep. Cats were implanted with electrodes in the frontal, parietal and occipital cortices to monitor EEG activity. The degree of coherence in the low (30-45. Hz) and high (60-100. Hz) gamma frequency bands from pairs of EEG recordings was analyzed. A large increase in coherence between all inter-hemispheric cortical regions in the low gamma bands during AW was present compared to the other behavioral states. Furthermore, both low and high gamma coherence between inter-hemispheric heterotopic cortices (different cortical areas of both hemispheres) decreased during REM sleep; this is a pattern that we previously reported between the cortical areas of the same hemisphere (intrahemispheric coherence). In the high gamma band, coherence during REM sleep also decreased compared to the other behavioral states. In contrast, between most of the inter-hemispheric homotopic cortical areas (equivalent or mirror areas of both hemispheres), low gamma coherence was similar during NREM compared to REM sleep. We conclude that in spite of subtle differences between homotopic and heterotopic inter-hemispheric cortices, functional interactions at high frequency decrease during REM sleep. © 2014 Elsevier Ireland Ltd.


Xi M.,WebSciences International | Chase M.H.,WebSciences International | Chase M.H.,University of California at Los Angeles
Sleep | Year: 2010

Study Objectives: We previously reported that the microinjection of hypocretin (orexin) into the nucleus pontis oralis (NPO) induces a behavioral state that is comparable to naturally occurring active (rapid eye movement) sleep. However, other laboratories have found that wakefulness occurs following injections of hypocretin into the NPO. The present study tested the hypothesis that the discrepancy in behavioral state responses to hypocretin injections is due to the fact that hypocretin was not administered during the same states of sleep or wakefulness. Design: Adult cats were implanted with electrodes to record sleep and waking states. Hypocretin-1 (0.25 μL, 500μM) was microinjected into the NPO while the animals were awake or in quiet (non-rapid eye movement) sleep. Measurements and Results: When hyprocretin-1 was microinjected into the NPO during quiet sleep, active sleep occurred with a short latency. In addition, there was a significant increase in the time spent in active sleep and in the number of episodes of this state. On the other hand, the injection of hyprocretin-1 during wakefulness resulted not only in a significant increase in wakefulness, but also in a decrease in the percentage and frequency of episodes of active sleep. Conclusions: The present data demonstrate that the behavioral state of the animal dictates whether active sleep or wakefulness is induced following the injection of hypocretin. Therefore, we suggest that hypocretin-1 enhances ongoing states of wakefulness and their accompanying patterns of physiologic activity and that hypocretin-1 is also capable of promoting active sleep and the changes in various processes that occur during this state.


Devera A.,University of the Republic of Uruguay | Pascovich C.,University of the Republic of Uruguay | Lagos P.,University of the Republic of Uruguay | Falconi A.,University of the Republic of Uruguay | And 4 more authors.
Brain Research | Year: 2015

Hypothalamic neurons that utilize melanin-concentrating hormone (MCH) as a neuromodulator are localized in the postero-lateral hypothalamus and incerto-hypothalamic area. These neurons send dense projections to the dorsal raphe nucleus (DRN). Serotonergic neurons of the DRN are involved in the control of sleep and play a critical role in major depression. Previously, we demonstrated that microinjections of MCH into the DRN resulted in an increase in REM sleep and produce a depressive-like effect. In the present study we examined the mechanisms that mediate these effects by employing neuroanatomical and electrophysiological techniques. First, we determined that rhodamine-labeled MCH (R-MCH), when microinjected into the lateral ventricle, is internalized in serotonergic and non-serotonergic DRN neurons in rats and cats. These data strongly suggest that these neurons express MCHergic receptors. Second, in rats, we demonstrated that the microinjection of MCH into the lateral ventricle results in a significant decrease in the firing rate in 59% of the neurons recorded in the DRN; the juxtacellular administration of MCH reduced the discharge in 80% of these neurons. Some of the neurons affected by MCH were likely serotonergic on the basis of their electrophysiological and pharmacological properties. We conclude that MCH reduces the activity of serotonergic neurons of the DRN. These and previous data suggest that the MCHergic modulation of serotonergic activity within the DRN is involved in the regulation of REM sleep as well as in the pathophysiology of depressive disorders. © 2014 Elsevier B.V.

Loading Websciences International collaborators
Loading Websciences International collaborators