Asunto(s)
Neuronas Motoras/fisiología , Sueño/fisiología , Animales , Humanos , Vías Nerviosas/fisiologíaRESUMEN
In the rat, a species widely used to study the neural mechanisms of sleep and motor control, lingual electromyographic activity (EMG) is minimal during non-rapid eye movement (non-REM) sleep and then phasic twitches gradually increase after the onset of REM sleep. To better characterize the central neural processes underlying this pattern, we quantified EMG of muscles innervated by distinct subpopulations of hypoglossal motoneurons and nuchal (N) EMG during transitions from non-REM sleep to REM sleep. In 8 chronically instrumented rats, we recorded cortical EEG, EMG at sites near the base of the tongue where genioglossal and intrinsic muscle fibers predominate (GG-I), EMG of the geniohyoid (GH) muscle, and N EMG. Sleep-wake states were identified and EMGs quantified relative to their mean levels in wakefulness in successive 10 s epochs. During non-REM sleep, the average EMG levels differed among the three muscles, with the order being N>GH>GG-I. During REM sleep, due to different magnitudes of phasic twitches, the order was reversed to GG-I>GH>N. GG-I and GH exhibited a gradual increase of twitching that peaked at 70-120 s after the onset of REM sleep and then declined if the REM sleep episode lasted longer. We propose that a common phasic excitatory generator impinges on motoneuron pools that innervate different muscles, but twitching magnitudes are different due to different levels of tonic motoneuronal hyperpolarization. We also propose that REM sleep episodes of average durations are terminated by intense activity of the central generator of phasic events, whereas long REM sleep episodes end as a result of a gradual waning of the tonic disfacilitatory and inhibitory processes.
Asunto(s)
Encéfalo/fisiología , Nervio Hipogloso/citología , Neuronas Motoras/fisiología , Músculos/inervación , Sueño/fisiología , Médula Espinal/citología , Animales , Ondas Encefálicas/fisiología , Electroencefalografía/métodos , Electromiografía , Nervio Hipogloso/fisiología , Masculino , Ratas , Ratas Sprague-DawleyRESUMEN
Noradrenergic (NE) excitatory drive maintains activity of hypoglossal (XII) motoneurons during wakefulness. In predisposed persons, sleep-related decrements of NE cell activity may contribute to hypotonia of upper airway muscles innervated by XII motoneurons. The goal of this study was to determine whether NE neurons of the pontine A7 group, an anatomically identified source of NE projections to the XII nucleus, provide significant, endogenous NE excitatory drive to XII motoneurons. In anesthetized rats, we microinjected clonidine (0.75 mM, 20-40 nl), an alpha(2)-adrenergic receptor agonist that inhibits pontine NE cells, aiming at the A7 region. Nine injections were placed within 0.4 mm from the A7 group identified using tyrosine hydroxylase immunohistochemistry: they reduced XII nerve activity by 31.3+/-2.8% (standard error) and decreased the central respiratory rate by 6%. Another 21 injections, including eight placed near NE cells of the sub-coeruleus region, were made at distances over 0.5 mm from the A7 group and they did not alter either XII nerve activity or respiratory rate. In control experiments, clonidine injections into the A7 group preceded by injections of an alpha(2)-receptor antagonist, RS-79948, did not change XII nerve activity. Four experiments with unilateral clonidine injections into the A7 region and with Fos immunohistochemistry used as a marker of cell activity revealed that the percentage of Fos-positive A7 cells was significantly reduced on the injected side. There was also a significant positive correlation between Fos expression in A7 cells and XII nerve activity. Thus, decrements of NE excitatory drive from the A7 group may significantly reduce XII nerve activity. In obstructive sleep apnea patients, in whom the muscles innervated by XII motoneurons act as upper airway dilators, this may contribute to sleep-related respiratory disorders.
Asunto(s)
Nervio Hipogloso/fisiología , Inhibición Neural/fisiología , Neuronas/fisiología , Norepinefrina/metabolismo , Puente/citología , Agonistas alfa-Adrenérgicos/farmacología , Antagonistas Adrenérgicos alfa/farmacología , Análisis de Varianza , Animales , Presión Sanguínea/efectos de los fármacos , Clonidina/farmacología , Electroencefalografía/métodos , Regulación de la Expresión Génica/efectos de los fármacos , Isoquinolinas/farmacología , Masculino , Naftiridinas/farmacología , Inhibición Neural/efectos de los fármacos , Neuronas/efectos de los fármacos , Proteínas Oncogénicas v-fos/metabolismo , Ratas , Ratas Sprague-Dawley , Respiración/efectos de los fármacos , Tirosina 3-Monooxigenasa/metabolismoRESUMEN
Predicting the strain hardening properties of crystals constitutes a long-standing challenge for dislocation theory. The main difficulty resides in the integration of dislocation processes through a wide range of time and length scales, up to macroscopic dimensions. In the present multiscale approach, dislocation dynamics simulations are used to establish a dislocation-based continuum model incorporating discrete and intermittent aspects of plastic flow. This is performed through the modeling of a key quantity, the mean free path of dislocations. The model is then integrated at the scale of bulk crystals, which allows for the detailed reproduction of the complex deformation curves of face-centered cubic crystals. Because of its predictive ability, the proposed framework has a large potential for further applications.
RESUMEN
Pontine noradrenergic neurons of the locus coeruleus (LC) and sub-coeruleus (SubC) region cease firing during rapid eye movement sleep (REMS). This plays a permissive role in the generation of REMS and may contribute to state-dependent modulation of transmission in the CNS. Whether all pontomedullary catecholaminergic neurons, including those in the A1/C1, A2/C2 and A7 groups, have REMS-related suppression of activity has not been tested. We used Fos protein expression as an indirect marker of the level of neuronal activity and linear regression analysis to determine whether pontomedullary cells identified by tyrosine hydroxylase (TH) immunohistochemistry have reduced Fos expression following REMS-like state induced by pontine microinjections of a cholinergic agonist, carbachol in urethane-anesthetized rats. The percentage of Fos-positive TH cells was negatively correlated with the cumulative duration of REMS-like episodes induced during 140 min prior to brain harvesting in the A7 and rostral A5 groups bilaterally (P < 0.01 for both), and in SubC neurons on the side opposite to carbachol injection (P < 0.05). Dorsal medullary A2/C2 neurons did not exhibit such correlation, but their Fos expression (and that in A7, rostral A5 and SubC neurons) was positively correlated with the duration of the interval between the last REMS-like episode and the time of perfusion (P < 0.05). In contrast, neither of these correlations was significant for A1 /C1 or caudal A5 neurons. These findings suggest that, similar to the prototypic LC neurons, neurons of the A7, rostral A5 and A2/C2 groups have reduced or abolished activity during REMS, whereas A1 /IC1 and caudal A5 neurons do not have this feature. The reduced activity of A2/C2, A5 and A7 neurons during REMS, and the associated decrements in norepinephrine release, may cause state-dependent modulation of.transmission in brain somato- and viscerosensory, somatomotor, and cardiorespiratory pathways.
Asunto(s)
Tronco Encefálico/fisiología , Carbacol/administración & dosificación , Agonistas Colinérgicos/administración & dosificación , Neuronas/metabolismo , Proteínas Proto-Oncogénicas c-fos/biosíntesis , Sueño REM/fisiología , Anestésicos Intravenosos/farmacología , Animales , Tronco Encefálico/efectos de los fármacos , Catecolaminas/metabolismo , Electroencefalografía , Inmunohistoquímica , Masculino , Bulbo Raquídeo/efectos de los fármacos , Bulbo Raquídeo/fisiología , Microinyecciones , Neuronas/efectos de los fármacos , Puente/efectos de los fármacos , Puente/fisiología , Ratas , Ratas Sprague-Dawley , Tirosina 3-Monooxigenasa/biosíntesis , Uretano/farmacologíaRESUMEN
During plastic flow of crystalline solids, dislocations self-organize in the form of patterns, with a wavelength that is inversely proportional to stress. After four decades of investigations, the origin of this property is still under discussion. We show that dislocation patterns verifying the principle of similitude can be obtained from dynamics simulations of double slip. These patterns are formed in the presence of long- and short-range interactions, but they are not significantly modified when only short-range interactions are present. This new insight into dislocation patterning phenomena has important implications regarding current models.
RESUMEN
It is hypothesized that the suppression of motor activity (atonia) that occurs during REM sleep is caused by the combined inhibition of motoneurons by glycine or GABA and withdrawal of excitation mediated by serotonin and norepinephrine. However, it is not known whether these mechanisms can fully account for the atonia. In urethane-anesthetized, paralyzed and artificially ventilated rats, REM sleep-like episodes can be repeatedly elicited by microinjections of a cholinergic agonist, carbachol, into the dorsomedial pons. We used this model to determine whether microinjections of a combination of antagonists of serotonergic, adrenergic, GABA(A) and glycinergic receptors (methysergide, prazosin, bicuculline and strychnine) into the XII nucleus can abolish the carbachol-induced depression of XII motoneuronal activity. REM sleep-like episodes were elicited prior to, and at different times after, antagonist microinjections. In all six rats studied, the depression of XII motoneuronal activity did not occur when tested 30-60 min after the antagonists, whereas other characteristic features of the response (latency, duration, the appearance of hippocampal theta rhythm, activation of the cortical EEG, slowing of the respiratory rate) remained intact. The carbachol-induced depression partially recovered after 2-3 hours. We conclude that the REM sleep-like depression of XII motoneuronal activity can be fully accounted for by all or some of the following mechanisms: a withdrawal of motoneuronal excitation mediated by norepinephrine and serotonin and increased inhibition mediated by GABA and glycine.
Asunto(s)
Nervio Hipogloso/fisiología , Bulbo Raquídeo/fisiología , Neuronas Motoras/fisiología , Inhibición Neural/fisiología , Receptores de Neurotransmisores/metabolismo , Sueño REM/fisiología , Potenciales de Acción/efectos de los fármacos , Potenciales de Acción/fisiología , Antagonistas Adrenérgicos/farmacología , Animales , Agonistas Colinérgicos/farmacología , Antagonistas del GABA/farmacología , Glicina/metabolismo , Glicinérgicos/farmacología , Nervio Hipogloso/citología , Nervio Hipogloso/efectos de los fármacos , Masculino , Bulbo Raquídeo/citología , Bulbo Raquídeo/efectos de los fármacos , Neuronas Motoras/citología , Neuronas Motoras/efectos de los fármacos , Inhibición Neural/efectos de los fármacos , Vías Nerviosas/citología , Vías Nerviosas/efectos de los fármacos , Vías Nerviosas/fisiología , Norepinefrina/metabolismo , Puente/citología , Puente/efectos de los fármacos , Puente/fisiología , Ratas , Ratas Sprague-Dawley , Tiempo de Reacción/efectos de los fármacos , Tiempo de Reacción/fisiología , Receptores de Neurotransmisores/efectos de los fármacos , Serotonina/metabolismo , Antagonistas de la Serotonina/farmacología , Ácido gamma-Aminobutírico/metabolismoRESUMEN
We connected dislocation-based atomic-scale and continuum models of plasticity in crystalline solids through numerical simulations of dislocation intersections in face-centered cubic crystals. The results contradict the traditional assumption that strain hardening is governed by the formation of sessile junctions between dislocations. The interaction between two dislocations with collinear Burgers vectors gliding in intersecting slip planes was found to be by far the strongest of all reactions. Its properties were investigated and discussed using a multiscale approach.
RESUMEN
The mechanisms of dislocation intersection and strain hardening in fcc crystals are examined with emphasis on the process of junction formation and destruction. Large-scale 3D simulations of dislocation dynamics were performed yielding access for the first time to statistically averaged quantities. These simulations provide a parameter-free estimate of the dislocation microstructure strength and of its scaling law. It is shown that forest hardening is dominated by short-range elastic processes and is insensitive to the detail of the dislocation core structure.
RESUMEN
Instabilities of plastic flow in alloys and the associated deformation patterns are currently attracting a lot of attention. We comment on a recent investigation by Franklin et al. [Phys. Rev. E 62, 8195 (2000)] on one such type of instability, the Portevin-Le Chatelier effect, attempting to clarify a few points about the instability mechanism as well as the reported experimental results.
RESUMEN
The collective behavior of dislocations in jerky flow is studied in Al-Mg polycrystalline samples subjected to constant strain rate tests. Complementary dynamical, statistical, and multifractal analyses are carried out on the stress-time series recorded during jerky flow to characterize the distinct spatiotemporal dynamical regimes. It is shown that the hopping type B and the propagating type A bands correspond to chaotic and self-organized critical states, respectively. The crossover between these types of bands is identified by a large spread in the multifractal spectrum. These results are interpreted on the basis of competing scales and mechanisms.
RESUMEN
The cholinergic neurons of the pedunculopontine and laterodorsal tegmental nuclei (PPN and LDN) increase their activity during wakefulness and REM sleep and interact with brainstem neurons containing serotonin (5-HT) and other amines. To determine whether mesopontine neurons that contain nitric oxide synthase (NOS), a marker for cholinergic cells, express 5-HT(2A) receptors, dual immunostaining for 5-HT(2A) receptor-like protein and NOS was employed with either peroxidase or fluorescent secondary probes. Within the PPN and LDN, different cells expressed 5-HT(2A) receptors and NOS. In addition to the lack of co-localization, the 5-HT(2A) receptor-expressing cells were smaller and less numerous than the adjacent NOS neurons. We propose that 5-HT(2A) receptor-expressing cells are local inhibitory interneurons whose one function is to ensure the reciprocal patterns of activity in subpopulations of mesopontine cholinergic and aminergic neurons.
Asunto(s)
Acetilcolina/metabolismo , Fibras Colinérgicas/metabolismo , Interneuronas/metabolismo , Inhibición Neural/fisiología , Puente/metabolismo , Receptores de Serotonina/metabolismo , Tegmento Mesencefálico/metabolismo , Animales , Especificidad de Anticuerpos , Recuento de Células , Fibras Colinérgicas/ultraestructura , Inmunohistoquímica/métodos , Interneuronas/citología , Masculino , Óxido Nítrico/metabolismo , Óxido Nítrico Sintasa/metabolismo , Puente/citología , Núcleos del Rafe/citología , Núcleos del Rafe/metabolismo , Ratas , Ratas Sprague-Dawley , Receptor de Serotonina 5-HT2A , Serotonina/metabolismo , Sueño/fisiología , Transmisión Sináptica , Tegmento Mesencefálico/citología , Vigilia/fisiologíaRESUMEN
Norepinephrine (NE) is an important modulator of brainstem motoneurons. It is released at high levels during wakefulness, whereas its reduced release during sleep may contribute to motor suppression, including upper airway hypotonia. To identify the receptors that mediate postsynaptic effects of NE in brainstem motoneurons of juvenile and adult rats, we determined the pattern of adrenoceptor mRNA expression and co-expression in retrogradely labeled and acutely dissociated hypoglossal (XII) motoneurons (n=121) using single-cell, real-time reverse transcription-polymerase chain reaction (RT-PCR). The alpha(1B) receptor mRNA was present in most motoneurons (33/39 or 85%). The remaining six adrenoceptor mRNA species investigated were consistently present in micropunches of tissue extracted from the XII nucleus, but were either rarely expressed in individual motoneurons (alpha(1A) mRNA in 15%, alpha(1D) in 14%, alpha(2B/C) in 2% of cells) or absent (alpha(2A), beta(1) and beta(2)). When present, the alpha(1A) and alpha(1D) mRNAs were co-expressed with alpha(1B) mRNA. The adrenoceptor mRNA expression profiles in dissociated locus coeruleus and inferior olive neurons were significantly different. We conclude that postsynaptic effects of NE in XII motoneurons are primarily mediated by alpha(1B) receptors; the effects ascribed to alpha(2) and/or beta adrenoceptors may be exerted presynaptically.
Asunto(s)
Tronco Encefálico/metabolismo , Nervio Hipogloso/metabolismo , Neuronas Motoras/metabolismo , Norepinefrina/metabolismo , Receptores Adrenérgicos alfa 1/genética , Membranas Sinápticas/metabolismo , Transmisión Sináptica/fisiología , Animales , Células Sanguíneas/metabolismo , Tronco Encefálico/citología , Nervio Hipogloso/citología , Locus Coeruleus/citología , Locus Coeruleus/metabolismo , Neuronas Motoras/citología , Núcleo Olivar/citología , Núcleo Olivar/metabolismo , ARN Mensajero/metabolismo , Ratas , Reacción en Cadena de la Polimerasa de Transcriptasa Inversa , Sueño/fisiologíaRESUMEN
We describe a cuff-type electrode specifically designed for recording from, and electrical stimulation of, cut nerves in acute experiments on small animals. Unlike existing designs of cuff electrodes, it is simple to manufacture, inexpensive and takes little time to implant. The electrode was tested on the hypoglossal, phrenic, recurrent laryngeal, and superior laryngeal nerves in anesthetized rats. It provides satisfactory signal-to-noise ratios (3.0+/-0.8 (mean+/-S.D.)) for hypoglossal and 5.4+/-2.1 for phrenic nerve activity and stable recording over the time course of a typical acute experiment. It eliminates or minimizes the problems with recording stability and space availability associated with conventional hook-type electrodes, and reduces experiment preparation time. This should facilitate neurophysiological experiments on small rodents involving complex protocols that include recording from, and/or stimulation of, multiple nerves.
Asunto(s)
Electrodos , Electrofisiología/instrumentación , Nervio Hipogloso/fisiología , Nervios Laríngeos/fisiología , Nervio Frénico/fisiología , Animales , Diseño de Equipo , Ratas , Ratas Sprague-DawleyRESUMEN
Since the early '60s, injections of a broad-spectrum muscarinic cholinergic agonist, carbachol, into the medial pontine reticular formation (mPRF) of cats have been extensively used as a tool with which to study the neural mechanisms of rapid eye movement (REM) sleep. During the last decade, new carbachol models of REM sleep were introduced, including chronically instrumented/behaving rats and "reduced" preparations such as decerebrate or anesthetized cats and rats. The combined results from these distinct models show interspecies similarities and differences. The dual nature, both REM sleep-promoting and wakefulness (or arousal)-promoting, of the cholinergic effects exerted within the mPRF is more strongly expressed in rats than in cats. This strengthens the possibility suggested by earlier central neuronal recordings that active wakefulness and REM sleep have extensive common neuronal substrates, and may have evolved from a common behavioral state. Carbachol studies using different intact and reduced models also suggest that powerful REM sleep episode-terminating effects originate in suprapontine structures. In contrast, the timing of REM sleep-like episodes in decerebrate models is determined by a pontomedullary neuronal network responsible for the generation of an ultradian cycle similar to the basic rest-activity cycle of N. Kleitman. Other presumed species differences, such as the more widespread distribution of carbachol-sensitive sites or the relative failure of carbachol to increase the duration of REM sleep episodes in rats when compared to cats, may be of a quantitative or technical nature. While carbachol and many other neurotransmitters and peptides microinjected into the mPRF evoke, enhance or suppress REM sleep, the most sensitive site(s) of their actions have not been fully mapped, and the nature of the cellular and neurochemical interactions taking place at the sites where carbachol triggers the REM sleep-like state remain largely unknown. Similarly, little is known about the pathways between the mPRF and medial medullary reticular formation, but the existing evidence suggests that they are reciprocal and essential for the generation of both natural and carbachol-induced REM sleep. Studies of the mesopontine cholinergic neurons, which are hypothesized to be the main source of endogenous acetylcholine for the mPRF, need to be extended to neurons of the mPRF and cells located functionally downstream from this important site for REM sleep, or both REM sleep and active wakefulness.
Asunto(s)
Carbacol/farmacología , Agonistas Colinérgicos/farmacología , Modelos Neurológicos , Red Nerviosa/efectos de los fármacos , Sueño REM/efectos de los fármacos , Sueño REM/fisiología , Animales , Gatos , Humanos , Bulbo Raquídeo/citología , Bulbo Raquídeo/efectos de los fármacos , Bulbo Raquídeo/metabolismo , Red Nerviosa/citología , Red Nerviosa/metabolismo , Puente/citología , Puente/efectos de los fármacos , Puente/metabolismo , Ratas , Formación Reticular/citología , Formación Reticular/efectos de los fármacos , Formación Reticular/metabolismoRESUMEN
In individuals with compromised upper airway anatomy, genioglossus (GG), the main protruder muscle of the tongue, is an important upper airway dilator which helps prevent upper airway obstructions. During rapid eye movement (REM) sleep, both the tonic and inspiratory-modulated components of GG activity are suppressed in parallel with the characteristic postural atonia. We tested whether the REM sleep-related reduction in the respiratory activity of GG may, in part, result from a reduced inspiratory drive relayed to hypoglossal (XII) motoneurons from their premotor medullary inspiratory neurons. In 15 urethane-anesthetized, paralyzed, vagotomized and artificially ventilated rats, we recorded XII nerve activity and the extracellular activity of medullary inspiratory-modulated neurons antidromically activated with latencies of 0.8 ms +/- 0.3(SD) from within (n = 19) or adjacent to (n = 11) the XII nucleus. Carbachol (10-20 nl, 10 mM), a cholinergic agonist, was microinjected into the dorsomedial pons. Such injections trigger a REM sleep-like state in chronically instrumented, intact animals and, in anesthetized rats, produce respiratory and electrocortical changes similar to those of REM sleep. Following the injections, the respiratory component of XII nerve activity was depressed by 51 +/- 22%, while the mean inspiratory firing rate of the neurons decreased by only 7.4 +/- 13.8% (from 69 +/- 34 Hz to 65 +/- 37 Hz; P < 0.02; n = 30). The activity of ventral respiratory group (VRG) and reticular formation inspiratory neurons with axons within the XII nucleus was reduced by 10 +/- 14% (P < 0.005; n = 19), whereas the activity of neurons located near the VRG that had axons passing below the XII nucleus did not change (n = 5). Thus, the depressant effect of carbachol on medullary inspiratory neurons was slightly more pronounced in reticular formation and VRG cells premotor to XII motoneurons than in other medullary inspiratory cells. For all cells, the magnitude of the decrease of cell activity was not related to the magnitude of depression of XII nerve activity, the simultaneously occurring decrease in respiratory rate or the cell's control firing rate. Since the magnitude of this depressant effect on all cell types was disproportionately small when compared with the depression of XII nerve activity, the REM sleep-like decrease in GG activity must be mainly mediated by non-respiratory premotor pathways.
Asunto(s)
Carbacol/farmacología , Nervio Hipogloso/fisiología , Inhalación/fisiología , Neuronas Motoras/fisiología , Neuronas/fisiología , Puente/fisiología , Sueño REM/fisiología , Animales , Carbacol/administración & dosificación , Nervio Hipogloso/efectos de los fármacos , Microinyecciones , Neuronas Motoras/efectos de los fármacos , Vías Nerviosas/efectos de los fármacos , Vías Nerviosas/fisiología , Neuronas/efectos de los fármacos , Puente/efectos de los fármacos , Ratas , Ratas Sprague-Dawley , Tiempo de Reacción , Lengua/inervación , VagotomíaRESUMEN
Serotonin (5-HT) exerts excitatory effects in many brainstem regions involved in autonomic, somatic, motor, and sensory functions, and in control of vigilance. To determine the potential role of 5-HT2A receptors in these effects, we immunohistochemically mapped the distribution of 5-HT2A receptor-like protein in the rat pontomedullary brainstem. Areas containing the densest labeling included the trigeminal, facial, hypoglossal, dorsal vagal motor nuclei, medullary linear nucleus, and the inferior olive. In the nucleus ambiguus, labeled cells were located in the areas containing pharyngeal and laryngeal motoneurons. Intensely labeled cells were loosely scattered in the reticular formation adjacent to the raphe magnus and obscurus nuclei, in the gigantocellular region, in the caudal pedunculopontine and laterodorsal tegmental nuclei, dorsomedial pontine reticular formation, and nucleus subcoeruleus. In the nucleus prepositus hypoglossi, all vestibular, abducens, cuneate, and lateral reticular nuclei, labeled neurons commingled with unlabeled ones. Few labeled neurons were located in the rostral and caudal ventrolateral medulla and parvicellular reticular formation. In the nucleus of the solitary tract, two patches of diffuse labeling not associated with cellular profiles were present: one in the medial, and the other in the interstitial subnucleus. Similar diffuse labeling was present in the lateral parabrachial region and the lateral rim of the caudal spinal trigeminal sensory nucleus. No labeled cells were found in the locus coeruleus, dorsal raphe, superior olive, or area postrema. The distinct pontomedullary distribution of 5-HT2A receptors, combined with the known arousal-dependent activity of serotonergic neurons, show that these receptors may mediate post- and presynaptic effects in the motor, selected somatic and visceral sensory, oculo-vestibulo-precerebellar, and sleep-related regions.
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Bulbo Raquídeo/metabolismo , Puente/metabolismo , Ratas/metabolismo , Receptores de Serotonina/metabolismo , Animales , Sistema Nervioso Autónomo/fisiología , Cerebelo/fisiología , Músculos Faciales/fisiología , Inmunohistoquímica , Bulbo Raquídeo/fisiología , Boca , Músculo Esquelético/fisiología , Músculos Oculomotores/fisiología , Puente/fisiología , Ratas Sprague-Dawley , Receptor de Serotonina 5-HT2A , Formación Reticular/fisiología , Distribución Tisular , Vestíbulo del Laberinto/fisiologíaRESUMEN
The effect of a single nucleotide polymorphism, a glutamine to arginine amino acid substitution in the human Timeless gene (Q831R, A2634G), on diurnal preferences was studied in a random sample of normal volunteers enrolled in a population-based epidemiology study of the natural history of sleep disorders. We genotyped 528 subjects for this single nucleotide polymorphism and determined morningness-eveningness tendencies using the Horne-Ostberg questionnaire. Our results indicate that Q831R Timeless has no influence on morningness- eveningness tendencies in humans.
Asunto(s)
Ritmo Circadiano/fisiología , Polimorfismo de Nucleótido Simple , Factores de Transcripción/genética , Adulto , Alelos , Proteínas de Ciclo Celular , Ritmo Circadiano/genética , ADN/genética , Femenino , Frecuencia de los Genes , Genotipo , Humanos , Péptidos y Proteínas de Señalización Intracelular , Masculino , Persona de Mediana EdadRESUMEN
Microinjection of a cholinergic agonist, carbachol, into the pontine reticular formation of chronically instrumented intact or acutely decerebrate rats and cats has been used extensively to study rapid eye movement sleep mechanisms. In this study, we sought to develop a reduced carbachol model of rapid eye movement sleep-like neural events exhibiting multiple physiological markers of this state, and allowing for the use of invasive electrophysiological techniques. Accordingly, we investigated whether pontine carbachol could produce rapid eye movement sleep-like motor atonia and electrocortical changes in urethane-anaesthetized rats. We recorded cortical and hippocampal electroencephalograms and genioglossus and inspiratory intercostal muscle activities in 13 urethane-anaesthetized, spontaneously breathing, tracheotomized and vagotomized rats. In steady-state periods with high-voltage/low-frequency electroencephalogram activity, carbachol microinjections (15-40 nl, 10 mM) were placed in the medial pontine reticular formation. In 12 rats, carbachol elicited episodes of stereotyped hypotonia of genioglossus but not intercostal muscle activity, typical of rapid eye movement sleep, with a latency and duration of 2.2+/-0.3min (mean+/-S.E.M.) and 11.0+/-2.9 min, respectively. In four of these rats, also similar to rapid eye movement sleep, the major suppression of genioglossus activity (-74+/-9%) was accompanied by electroencephalogram desynchronization, appearance of hippocampal theta rhythm, and a respiratory rate increase (+ 14+/-3%). In the remaining eight rats, the stereotyped suppression of genioglossus activity (-48+/-3%) occurred without electroencephalogram desynchronization and hippocampal theta, and was accompanied by a respiratory rate decrease (-6+/-2%); a pattern of response typical of decerebrate animals. Within a rat, similar patterns of response to repeated carbachol injections at the same anatomical site were obtained. Pontine atropine prevented responses to subsequent carbachol injections. Thus, in urethane-anaesthetized rats, pontine carbachol consistently produced a differential suppression of pharyngeal versus respiratory pump muscle activity, and in a subset of animals, this was also accompanied by cortical and hippocampal electrographic changes typical of rapid eye movement sleep. This shows that complex and stereotyped neuronal events underlying both ascending and descending signs of rapid eye movement sleep can be pharmacologically activated under general anaesthesia. Such a reduced preparation may be useful for studies into the central neuronal mechanisms underlying generation of rapid eye movement sleep; particularly for studies requiring techniques that are difficult to implement in intact, naturally sleeping animals. The acceleration of the respiratory rate observed only when carbachol induced electroencephalogram desynchronization suggests that neural events associated with electrocortical changes contribute to the respiratory rate increases observed in natural rapid eye movement sleep.