Short-term deep brain stimulation of the thalamic reticular nucleus modifies aberrant oscillatory activity in a neurodevelopment model of schizophrenia.

Dysfunction of thalamo-cortical networks involving particularly the thalamic reticular nucleus (TRN) is implicated in schizophrenia. In the neonatal ventral hippocampal lesion (NVHL), a heuristic animal model of schizophrenia, brain oscillation changes similar to those of schizophrenic patients have been reported. The aim of this study was to analyze the effects of short-term deep brain stimulation (DBS) in the thalamic reticular nucleus on electroencephalographic (EEG) activity in the NVHL. Male and female Sprague-Dawley rats were used and the model was prepared by excitotoxicity damage of the ventral hippocampus on postnatal day 7 (PD-7). Chronic bilateral stainless steel electrodes were implanted in the TRN, thalamic dorsomedial nucleus and prelimbic area at PD-90. Rats were classified as follows: sham and NVHL groups, both groups received bilateral DBS in the TRN for one hour (100Hz, 100µs pulses, 200µA). All animals showed a sudden behavioral arrest accompanied by widespread symmetric bilateral spike-wave discharges, this activity was affected by DBS-TRN. Additionally, the power spectra of 0.5-100Hz and the coherence of 0.5-4.5 and 35-55Hz frequencies were modified by DBS-TRN. Our results suggest that DBS in the TRN may modify functional connectivity between different parts of the thalamo-cortical network. Additionally, our findings may suggest a beneficial effect of DBS-TRN on some preclinical aberrant oscillatory activities in a neurodevelopmental model of schizophrenia.

Neuropathic and inflammatory antinociceptive effects and electrocortical changes produced by Salvia divinorum in rats.

ETHNOPHARMACOLOGICAL RELEVANCE: Salvia divinorum is a medicinal plant traditionally used in hallucinogenic ethnopharmacological practices and for its analgesic and antinflammatory properties. Its active compounds include diterpenes known as salvinorins which act as potent κ opioid receptor agonists. AIM OF THE STUDY: Given its effects in acute animal models of pain, as well as its antinflammatory attributes, we decided to investigate the analgesic effects of an SD extract in neuropathic (sciatic loose nerve ligature) and inflammatory (intra plantar carrageenan) pain models in rats. We also determined in this study the electrocorticographic changes to correlate similar hallucinogenic state and behavior as those produced in humans. MATERIAL AND METHODS: Mechanical and thermonociceptive responses, plantar test and von Frey assay, respectively, were measured in adult Wistar rats 30min, 3h and 24h after the intraperitoneal administration of saline or an hydroponic SD extract. We also evaluated carbamazepine and celecoxib, as gold reference drugs, to compare its antinociceptive effects. RESULTS: Our results showed that administration of SD extract induced antialgesic effects in both neuropathic and inflammatory pain models. All those effects were blocked by nor-binaltorphimine (a Kappa opioid receptor antagonist). Moreover, it was observed an increase of the anterior power spectral density and a decrease in the posterior region as electrocorticographic changes. CONCLUSION: The present investigation give evidence that SD is capable to reduce algesic response associated to neuropathic and inflammatory nociception. This study support therapeutic alternatives for a disabling health problem due to the long term pain with high impact on population and personal and social implications.

Propylparaben applied after pilocarpine-induced status epilepticus modifies hippocampal excitability and glutamate release in rats.

Propylparaben (PPB) induces cardioprotection after ischemia-reperfusion injury by inhibiting voltage-dependent Na+ channels. The present study focuses on investigating whether the i.p. application of 178mg/kg PPB after pilocarpine-induced status epilepticus (SE) reduces the acute and long-term consequences of seizure activity. Initially, we investigated the effects of a single administration of PPB after SE. Our results revealed that compared to rats receiving diazepam (DZP) plus vehicle after 2h of SE, animals receiving a single dose of PPB 1h after DZP injection presented 126% (p<0.001) lower extracellular levels of glutamate in the hippocampus. This effect was associated with an increased potency of low-frequency oscillations (0.1-13Hz bands, p<0.001), a reduced potency of 30-250Hz bands (p<0.001) and less neuronal damage in the hippocampus. The second experiment examined whether the subchronic administration of PPB during the post-SE period is able to prevent the long-term consequences of seizure activity. In comparison to animals that were treated subchronically with vehicle after SE, rats administered with PPB for 5 days presented lower hippocampal excitability and interictal glutamate release, astrogliosis, and neuroprotection in the dentate gyrus. Our data indicate that PPB, when applied after SE, can be used as a therapeutic strategy to reduce the consequences of seizure activity.

Acute deep brain stimulation in the thalamic reticular nucleus protects against acute stress and modulates initial events of adult hippocampal neurogenesis.

Deep brain stimulation (DBS) is used as an alternative therapeutic procedure for pharmacoresistant psychiatric disorders. Recently the thalamic reticular nucleus (TRN) gained attention due to the description of a novel pathway from the amygdala to this nucleus suggesting that may be differentially disrupted in mood disorders. The limbic system is implicated in the regulation of these disorders that are accompanied by neuroplastic changes. The hippocampus is highly plastic and shows the generation of new neurons, process affected by stress but positively regulated by antidepressant drugs. We explored the impact of applying acute DBS to the TRN (DBS-TRN) in male Wistar rats exposed to acute stress caused by the forced-swim Porsolt's test (FST) and on initial events of hippocampal neurogenesis. After the first session of forced-swim, rats were randomly subdivided in a DBS-TRN and a Sham group. Stimulated rats received 10min of DBS, thus the depressant-like behavior reflected as immobility was evaluated in the second session of forced-swim. Locomotricity was evaluated in the open field test. Cell proliferation and doublecortin-associated cells were quantified in the hippocampus of other cohorts of rats. No effects of electrode implantation were found in locomotricity. Acute DBS-TRN reduced immobility in comparison to the Sham group (p<0.001). DBS-TRN increased cell proliferation (Ki67 or BrdU-positive cells; p=0.02, p=0.02) and the number of doublecortin-cells compared to the Sham group (p<0.02). Similar effects were found in rats previously exposed to the first session of forced-swim. Our data could suggest that TRN brain region may be a promising target for DBS to treat intractable depression.

Involvement of the GABAergic system in the neuroprotective and sedative effects of acacetin 7-O-glucoside in rodents.

PURPOSE: Characterization of sedative, possible anticonvulsant, and protective effects of Acacetin-7-O-glucoside (7-ACAG). METHODS: 7-ACAG was separated and its purity was analyzed. Its sedative and anti-seizure effects (1, 10, 20, and 40 mg/kg) were evaluated in male mice. Synaptic responses were acquired from area CA1 of hippocampal slices obtained from male Wistar rats. Rats were subjected to stereotaxic surgeries to allow Electroencephalographic (EEG) recordings. Functional recovery was evaluated by measuring the time rats spent in completing the motor task. Then the rats were subjected to right hemiplegia and administered 7-ACAG (40 mg/kg) 1 h or 24 h after surgery. Brains of each group of rats were prepared for histological analysis. RESULTS: Effective sedative doses of 7-ACAG comprised those between 20 and 40 mg/kg. Latency and duration of the epileptiform crisis were delayed by this flavonoid. 7-ACAG decreased the synaptic response in vitro, similar to Gamma-aminobutyric acid (GABA) effects. The flavonoid facilitated functional recovery. This data was associated with preserved cytoarchitecture in brain cortex and hippocampus. CONCLUSIONS: 7-ACAG possesses anticonvulsive and sedative effects. Results suggest that GABAergic activity and neuroprotection are involved in the mechanism of action of 7-ACAG and support this compound's being a potential drug for treatment of anxiety or post-operative conditions caused by neurosurgeries.

Transcranial focal electrical stimulation reduces the convulsive expression and amino acid release in the hippocampus during pilocarpine-induced status epilepticus in rats.

The aim of the present study was to evaluate the effects of transcranial focal electrical stimulation (TFS) on γ-aminobutyric acid (GABA) and glutamate release in the hippocampus under basal conditions and during pilocarpine-induced status epilepticus (SE). Animals were previously implanted with a guide cannula attached to a bipolar electrode into the right ventral hippocampus and a concentric ring electrode placed on the skull surface. The first microdialysis experiment was designed to determine, under basal conditions, the effects of TFS (300 Hz, 200 µs biphasic square pulses, for 30 min) on afterdischarge threshold (ADT) and the release of GABA and glutamate in the hippocampus. The results obtained indicate that at low current intensities (<2800 µA), TFS enhances and decreases the basal extracellular levels of GABA and glutamate, respectively. However, TFS did not modify the ADT. During the second microdialysis experiment, a group of animals was subjected to SE induced by pilocarpine administration (300 mg/kg, i.p.; SE group). The SE was associated with a significant rise of GABA and glutamate release (up to 120 and 182% respectively, 5h after pilocarpine injection) and the prevalence of high-voltage rhythmic spikes and increased spectral potency of delta, gamma, and theta bands. A group of animals (SE-TFS group) received TFS continuously during 2h at 100 µA, 5 min after the establishment of SE. This group showed a significant decrease in the expression of the convulsive activity and spectral potency in gamma and theta bands. The extracellular levels of GABA and glutamate in the hippocampus remained at basal conditions. These results suggest that TFS induces anticonvulsant effects when applied during the SE, an effect associated with lower amino acid release. This article is part of a Special Issue entitled "Status Epilepticus".

Effect of vagus nerve stimulation on electrical kindling in different stages of seizure severity in freely moving cats.

Vagus nerve stimulation (VNS) is an adjunctive therapy for treating pharmacoresistant epilepsy. The present study analyze the effect of VNS on the epileptic activity of amygdala kindling (AK) in different seizure severity stages in freely moving cats. Fourteen adult male cats were used and were stereotaxically implanted in both amygdalae, in thalamic reticular nuclei and in prefrontal cortices. AK was developed by the application of 60Hz pulse trains that were one second in duration. VNS was applied the following day after the first stages were reached. This stimulation consisted of 10 pulse trains in the one-hour period (1min on/5min off) prior to AK. AK stimulation continued until all animals reached stage VI. The behavioral changes induced by VNS were transient and bearable. The animals showed relaxation of the nictitating membrane, ipsilateral anisocoria, swallowing and licking. Intermittent VNS application in stage I induced a delay in AK progression. The effect of VNS on the amygdala afterdischarge duration (AD) did not change progressively. VNS in stages II, III, and IV does not have an inhibitory effect on AK, and the AD further exhibited a progressive development. At the end of the generalized seizures, the animals presented with synchronized bilateral discharges of the spike-wave type (3Hz) and a behavioral "staring spell". Our results show that VNS applied during the different stages of seizure severity exerts an anti-epileptogenic effect in stage I but no anti-epileptogenic effect in stages II, III, and IV. These results suggest that VNS applied at stage I of kindling induces a delay of generalized convulsive activity.

Electroencephalographic activity in neonatal ventral hippocampus lesion in adult rats.

A neonatal ventral hippocampal lesion (NVHL) in rats has been commonly used as a neurodevelopmental model to mimic schizophrenia-like behaviors. Recently, we reported that NVHL resulted in dendritic retraction and spine loss in pyramidal neurons of the prefrontal cortex (PFC). In addition, the hippocampus and PFC are important structures in the regulation of the electroencephalographic (EEG) activity. Patients with PFC lesions show deficits in the EEG activity. This study aimed to determine whether the EEG activity was altered in NVHL rats. In addition, we also analyzed the locomotor activity induced by a novel environment and exploratory behavior using the hole-board test. Consistent with the behavioral findings, the EEG analysis of the cortical regions showed that the NVHL rats displayed a lower power in cortical bands. At 1-8 Hz, 9-14 Hz, and 15-30 Hz bands, our findings showed a decrease in the absolute power of the parietal and occipital cortices recordings. In addition, the NVHL rats also showed a reduction in the exploratory behavior tested using the hole-board test. In conclusion, this study demonstrated that the EEG activity was reduced in adult NVHL rats and suggests that this may play a role in the behavioral changes observed in this neurodevelopmental model of schizophrenia.

An agonist-antagonist cerebellar nuclear system controlling eyelid kinematics during motor learning.

The presence of two antagonistic groups of deep cerebellar nuclei neurons has been reported as necessary for a proper dynamic control of learned motor responses. Most models of cerebellar function seem to ignore the biomechanical need for a double activation-deactivation system controlling eyelid kinematics, since most of them accept that, for closing the eyelid, only the activation of the orbicularis oculi (OO) muscle (via the red nucleus to the facial motor nucleus) is necessary, without a simultaneous deactivation of levator palpebrae motoneurons (via unknown pathways projecting to the perioculomotor area). We have analyzed the kinetic neural commands of two antagonistic types of cerebellar posterior interpositus neuron (IPn) (types A and B), the electromyographic (EMG) activity of the OO muscle, and eyelid kinematic variables in alert behaving cats during classical eyeblink conditioning, using a delay paradigm. We addressed the hypothesis that the interpositus nucleus can be considered an agonist-antagonist system controlling eyelid kinematics during motor learning. To carry out a comparative study of the kinetic-kinematic relationships, we applied timing and dispersion pattern analyses. We concluded that, in accordance with a dominant role of cerebellar circuits for the facilitation of flexor responses, type A neurons fire during active eyelid downward displacements-i.e., during the active contraction of the OO muscle. In contrast, type B neurons present a high tonic rate when the eyelids are wide open, and stop firing during any active downward displacement of the upper eyelid. From a functional point of view, it could be suggested that type B neurons play a facilitative role for the antagonistic action of the levator palpebrae muscle. From an anatomical point of view, the possibility that cerebellar nuclear type B neurons project to the perioculomotor area-i.e., more or less directly onto levator palpebrae motoneurons-is highly appealing.

Preemptive effect of nucleus of the solitary tract stimulation on amygdaloid kindling in freely moving cats.

PURPOSE: The nucleus of the solitary tract (NTS) is a primary site where vagal afferents terminate. The aim of this study was to analyze the preemptive effect of NTS electrical stimulation on daily amygdaloid kindling (AK) in freely moving cats. METHODS: Seven adult male cats were used. Bipolar electrodes were stereotaxically implanted into both amygdalae, lateral geniculate bodies, hippocampi, and prefrontal cortices. In addition, a bipolar stainless steel electrode was implanted in the left NTS. Cats were recorded under the following experimental conditions: The NTS was stimulated for 6 days before the initiation of AK (1 min on/5 min off, 1 h total). AK was performed by stimulating the amygdala every 24 h (1 s, 60 Hz, 1 ms) until behavioral stage VI was reached. RESULTS: The number of stimulations to reach stage VI in control animals was 23.4 +/- 3.7, in lateral tegmental field (LTF) animals was 17.0 +/- 2.1 days. Animals subjected to preemptive NTS stimulation showed a significant increase (53.8 +/- 5.9). In addition, behavioral development was retarded, with an increase in the number of stimulations required to reach stage III. In this group, overall kindling development was delayed, and amygdaloid afterdischarge duration did not show a progressive increase as was observed in the control group. DISCUSSION: Our results indicate that preemptive NTS electrical stimulation interferes with epileptogenesis. This anticonvulsive effect could be related to the activation of certain structures that inhibit seizure development. Therefore, results suggest that NTS mediates the anticonvulsive effect of vagus nerve stimulation.

Effects of electrical stimulation of the vagus nerve on the development of visual habituation in the cat.

The vagus nerve participates in the control and regulation of important autonomous functions, emotional tasks, and neural activity. Electrical vagus nerve stimulation (VNS) is an approved procedure for the treatment of refractory epilepsy in humans. VNS has also been shown to improve mood complaints and cognitive function in both human patients and animals. Thus, the purpose of this study was to analyse and describe the effects of VNS on the development and establishment of sensory habituation and electrographic activity of the visual pathway in freely moving cats. Six cats had implants placed in the optic chiasm (OC), lateral geniculate body (LGB), mesencephalic reticular formation (MRF), primary visual cortex (VC) of the left hemisphere, and left vagus nerve. Immediately after surgery, all cats presented anisocoria and relaxation of the left nictitant membrane. Also showed vegetative-type responses such as myosis, licking, and swallowing during VNS. Animals were then subjected to repeated luminous stimuli at intervals of 1 and 3s to cause habituation. The effect of VNS on the frequency and latency of the habituation episodes and the electrographic changes in the registered brain structures were analysed. Latency analysis showed that VNS delayed the first habituation episode. VNS had transitory effects on the neural activity of the primary visual pathway structures, which caused a small but measurable delay in the establishment of habituation. In conclusion, VNS interferes with the development and establishment of visual habituation, an elementary form of non-associative learning, in freely moving cats.

Long-term changes in sleep and electroencephalographic activity by chronic vagus nerve stimulation in cats.

We previously reported the effect of vagus nerve electrical stimulation (VNS) on sleep and behavior in cats. The aim of the present study is to analyze the long-term effects of VNS on the electroencephalographic (EEG) power spectrum and on the different stages of the sleep-wakefulness cycle in the freely moving cat. To achieve this, six male cats were implanted with electrodes on the left vagal nerve and submitted to 15 rounds of 23 h continuous sleep recordings in three categories: baseline (BL), VNS and post-stimulus recording (PSR). The following parameters were analyzed: EEG power spectrum, total time and number of sleep phases, ponto-geniculo-occipital (PGO) wave density of the rapid eye movement (REM) sleep, and the number of times the narcoleptic reflex was present (sudden transition from wakefulness to REM sleep). Significant changes were detected, such as an enhancement of slow-wave sleep (SWS) stage II; a power increase in the bands corresponding to sleep spindles (8-14 Hz) and delta waves (1-4 Hz) with VNS and PSR; an increase in the total time, number of stages, and density of PGO wave in REM sleep with VNS; a decrease of wakefulness in PSR, and the eventual appearance of the narcoleptic reflex with VNS. The results show that the effect of the VNS changes during different stages of the sleep-wakefulness cycle. In REM sleep, the effect was present only during VNS, while the SWS II was affected beyond VNS periods. This suggests that ponto-medullar and thalamic mechanisms of slow EEG activity may be due to plastic changes elicited by vagal stimulation.

Mapeo cortical que muestra el efecto de las encefalinas en un foco epiléptico

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Abstract: Introduction. Epileptic activity modifies the endogenous opioid system by increasing its levels at the end of the ictal phase, and in post-ictal and interictal phases. This increase originates a cortical excitatory effect which suppresses both slow wave sleep and REM. The epileptic activity is initiated with the presence of interictal epileptiform activity, which may be induced through penicillin administration into amygdaline nuclei. Interictal epileptiform activity is a widely employed tool used to determine the localization of epileptic foci characterized by the sudden presence of spikes or acute waves in an electroencephalogram (EEG). In the present work, this tool was used to study the participation of the opioid system in the installation and propagation of epileptic activity induced in temporal lobe amygdala. In the epiloptogenetic study, amygdaline interictal epileptiform activity was used to assess changes induced by opioids and an antagonist in the occurrence of interictal activity using an event histogram. Propagation was studied with the cortical topographic mapping technique, which shows EEG frequency components in a power spectrum, as well as the rhythmic EEG patterns. The aim of the present study was to analyze the effect of enkephalins on epileptiform activity induced with penicillin in tem poral lobe amygdala and its propagation to the cerebral cortex. Method. Fifteen male Wistar rats were submitted to an acute preparation; they were anesthetized with urethane (1.2 g/kg, i.p.). A stainless steel bipolar electrode provided with a cannula was directed toward the left amygdaline basolateral nucleus and a second concentric bipolar electrode to the right amygdaline basolateral nucleus. Two types of cortical recordings were carried out: global mapping and restricted areas. The first consisted of the placement of a 16 stainless steel electrode matrix (in which the electrodes from the vertex were removed) on the scalp, taking care that the tips of the electrodes were in contact with the cortex; this arrangement covered the whole cerebral cortex. The second involved a 4x4mm square matrix consisting of 16 equidistant electrodes placed on the cerebral cortex. The cortical recording was a result of placing this matrix in four different positions so that the whole cerebral cortex was monitored. To monitor cortical recordings, experimental groups were injected penicillin into the amygdaline nuclei. To perform global mapping, enkephalins, [D-ala]-methionine and [D-ala]-leucine, were topically applied into the amygdaline nuclei and naloxone was administered systemically. Analogical signals were recorded in a video-tape and were digitized in parallel with an HP workstation. Off-line analysis was carried as follows: a) information recorded in video-tapes was acquired in a computer designed for this purpose, using amygdaline interictal epileptiform activity to plot event histograms; b) EEG digitized signal, obtained from global mapping, was used to obtain a spectral analysis, consisting of color images maps in time and frequency domains, using RBEAM software. The recording of electrical activity obtained with the square matrix was visually analyzed only. At the end of each experiment, animals were perfused and each brain was fixed intracardially with 10% formaldehyde. To verify the recording and sub-cortical injection sites, the rapid procedure was used. Results. During control stages, cortical records showed slow activity in the form of spindles in all the recording channels; this was due to urethane. Penicillin administration in amygdaline nuclei induced epileptiform activity with a specific pattern: immediate appearance after penicillin application with a gradual increase in amplitude until stabilization was reached within 5-10 minutes of administration. Analyses of global mapping in the frequency domain showed a specific mode of amygdaline interictal epileptiform activity propagation, starting in ipsilateral temporal, prefrontal and fron tal cortices, appearing subsequently in contralateral prefrontal and frontal cortices, and finally in temporal cortex. In the time domain spectrum, an electric dipole generating an interictal spike was found in cerebral cortex. Restricted areas mapping approach showed interictal epileptiform activity and its propagation along the ipsilateral fronto-temporal region. Data revealed an antero-posterior medial cortical activation spreading with decreasing intensity toward occipital regions. Application of enkephalins-[D-ala]-methionine and [D-ala]-leucine produced no epileptic activity, but an increase in basal EEG of cortical epileptiform activity was detected, as well as a decrease in amplitude and frequency of amygdaline epileptiform activity. Naloxone originated a facilitatory effect, since its administration induced focal and generalized electrocorticographic seizures. Conclusions. Focal penicillin is a reliable model of interictal spikes, paroxysms and generalized seizures. The study in rats showed a propagation of epileptic activity to prefrontal cortices prior to contralateral amygdala. Our results showed that enkephalins produced a double effect. First, they originated an increase in basal EEG in temporal cortical areas, as well as a putative participation in propagation mechanisms. Second, they exerted an inhibitory effect on epilepsy installation mechanisms. The inhibitory effect originated by enkephalins was reverted by naloxone.

Effect of electrical stimulation of the nucleus of the solitary tract on the development of electrical amygdaloid kindling in the cat.

PURPOSE: This work analyzed the effect of electrical stimulation of the nucleus of the solitary tract (NTS) on the development of electrical amygdaloid kindling (AK) in freely moving cats. METHODS: Nine male adult cats with implanted electrodes in both amygdalae (basolateral nucleus), both lateral geniculate bodies, left NTS, and both prefrontal cortices were used. Electromyogram and electrooculogram also were recorded. The AK was performed every 24 h (1-s train, 1-ms pulses, 60 Hz, 300-600 microA). The NTS was stimulated previously for 1 min (0.5-ms pulses, 30 Hz, 150-300 microA), just before the AK at 10:00 a.m., and then every 60 min, 4 times, from 11:00 a.m. to 2:00 p.m. On different days, all NTS stimulation was suspended, and AK was continued until stage VI kindling was reached. RESULTS: Behavioral changes produced by the stimulation of the NTS were blinking, immobility periods with upward sight, licking, and swallowing. Animals with simultaneous stimulation of NTS and AK did not reach stage VI, remaining in behavioral stages I-III. Stage VI was reached after NTS stimulation was intentionally suspended. The amplitude, duration, and the propagation of the amygdaloid afterdischarge did not exhibit progressive evolution during NTS stimulation. A regression analysis was performed between the number of days with only AK stimulation and days with simultaneous NTS stimulation, which showed a positive correlation (values of r = 0.84). CONCLUSIONS: Our results suggest that NTS stimulation interferes with the development of convulsive evolution and secondary generalization. This delay effect may be due to the activation of the locus ceruleus and some areas of the midbrain reticular formation, among other structures, which has been demonstrated to inhibit experimental convulsive seizures.

Chronic stimulation of the cat vagus nerve: effect on sleep and behavior.

The effect of electrical vagus nerve stimulation (VNS) on sleep and behavior was analyzed in freely moving cats. Eight cats were prepared for 23-h sleep recordings. The left vagus nerve of four of them was stimulated during 1 min, five times at 1-h intervals, for 5 days. The VNS induces: ipsilateral myosis, blinking, licking, abdominal contractions, upward gaze, swallowing, and eventually yawning and compulsive eating, as well as an increase of ponto-geniculate-occipital (PGO) wave density and of the number of stages and total amount of rapid eye movement (REM) sleep. Besides, there was a sudden transition from waking stage to REM sleep. The present results suggest that VNS modifies sleep in the cat. This effect could be explained by an activation of the areas involved in the physiological mechanisms of sleep.

Effect of the administration of gabaergic agonists of the GABA A/BDZ receptor on sleep in human subjects

El objetivo de este estudio ha sido evaluar los efectos de la administración aguda de una única dosis de una benzodiacepina de acción prolongada (diacepam, 10 mg), una imidazopiridina (zolpidem, 10 mg), una ciclopirrolona (zopiclona, 7.5 mg), un agonista del complejo molecular GABA A/BDZ (Gabob, 500 mg), y un placebo, sobre el sueño en diez sujetos sanos, utilizando un diseño doble-ciego de cuadrado latino de bloques incompletos. Para ello, se hizo un registro polisomnográfico nocturno (de ocho horas de duración) de cada sujeto durante seis noches consecutivas, en donde se evaluaban variables polisomnográficas relacionadas con la cantidad y la calidad de sueño. Nuestros resultados indicaron que no hubo ningún cambio significativo en las variables polisomnográficas relacionadas con la cantidad de sueño tras la administración de las sustancias. En cambio, los fármacos afectaron tres variables relacionadas con la calidad de sueño; en concreto, al porcentaje de la fase I de sueño, al de sueño; en concreto, al porcentaje de la fase I de sueño, al de sueño MOR (Movimientos Oculares Rápidos) y al de los episodios de la fase II. Por otra parte, nuestros resultados pusieron de manifiesto que la zopiclona fue la sustancia que produjo una mejoría significativa en las variables polisomnográficas relacionadas con la cantidad de sueño, cuando las comparaciones estadísticas se establecieron entre la línea base, la administración del fármaco y el periodo de levado del fármaco. No obstante, el placebo produjo un empeoramiento de las variables polisomnográficas relacionadas con la cantidad de sueño, evidenciándose un claro "efecto placebo" sobre las variables polisomnográficas

Visualización gráfica de las transiciones de las fases del sueño en el hombre: métodos de representación tridimensional / Graphic visualization of the transition of sleep phases in humans: methods of tridimensional representation

El método tradicional para analizar el electroencefalograma (EEG) durante el sueño se ha basado en la inspección visual, hoja por hoja, de los registros de varias horas de sueño de los sujetos, hombres o animales experimentales. Muchas de las características eléctricas pueden ser detectadas y analizadas utilizando este método, pero otras no. Esto se debe a que la inspección visual es un método en el dominio del tiempo, en el cual no son evidentes las frecuencias embebidas en el trazo, ni las relaciones de fase entre eventos electrográficos. En el EEG visualizado pueden medirse algunas características relacionadas con el dominio de la frecuencia, pero sólo en una forma elemental, es decir, la frecuencia y forma de una onda en particular. Pero los cambios sutiles en la fase y las desviaciones ligeras en las frecuencias escapan a la vista del observador. Otro obstáculo en la inspección visual del EEG es la cantidad de registro que se puede ver a la vez; usualmente, uno o dos páginas, lo que dificulta mucho la detección de los cambios leves de la frecuencia. Se ha diseñado y probado un método computacional que soluciona algunos de los problemas intrínsecos de la calificación tradicional del EEG, sobre todo en los registros de sueño de toda la noche. Este programa computacional puede generar una imagen que condensa la evolución de hasta 8 horas continuas de EEG, lo que representa una "abstracción" de la evolución del EEG en el dominio de la frecuencia. Para lograr esto, se calcula el espectro de potencia de cada época de 4 segundos durante toda la noche de registro, y se grafica como una imagen trimensional sólida. Además, se puede graficar simultáneamente la potencia en otros canales del registro, como el electrooculograma (EOG) y el electromiograma (EMG), con el fin de lograr una visualización inmediata de las transiciones de las fases del sueño durante el registro. Se obtuvieron datos de la aplicación de este programa en los registros del EEG (8 horas) de seres humanos. El programa computacional que se presenta fue escrito y probado en una ULTRA SPARC Creator I. utilizando compiladores C++ GNU

La activación progresiva del sistema límbico (Kindling): un modelo de aprendizaje y plasticidad cerebral / Progressive activation of the limbic system (Kindling): a learning and brain plasticity model

Después de una breve revisión del concepto de Sistema Límbico (SL), se describen una serie de experimentos de nuestro laboratorio, utilizando el análisis de potenciales evocados sensoriales y repuestas paroxísticas en diversos modelos de epilepsia experimental: metrazol, electrochoque, focos corticales con cobalto, aplicación tópica repetida de penicilina y estimulación eléctrica breve y periódica de la amígdala del lóbulo temporal (kindling). Estos dos últimos modelos, por su cronicidad y permanencia, nos han permitido establecer medidas de cambios plásticos cerebrales con localizaciones precisas. En estos experimentos se implementaron programas para el análisis computacional (RFM) de la posdescarga paroxística y de las respuestas eléctricas sensoriales. Se describen las modificaciones en la organización del sueño, así como el efecto inhibidor del sueño paradójico o MOR sobre los paroxismos del Kindling químico o eléctrico