RESUMEN
BACKGROUND: The dorsolateral prefrontal cortex (DLPFC) plays an important role in the regulation of food intake. Several previous studies demonstrated that a single session of transcranial direct current stimulation (tDCS) of the DLPFC reduces food craving and caloric intake. OBJECTIVES: We hypothesized that repeated tDCS of the right DLPFC cortex may exert long-term changes in food craving in young, healthy adults and that these changes may differ between normal and overweight subjects. METHODS: Thirty healthy individuals who reported frequent food cravings without a prior history of eating disorders were initially recruited. Subjects were randomized into an ACTIVE group who received 5 days of real tDCS (20 minutes, anode right-cathode left montage, 2 mA with current density kept at 0.06 mA/cm2, 1 min ramp-up/ramp-down), and a SHAM group, who received one day of real tDCS, on the first day (same parameters), followed by 4 days of sham tDCS. Food craving intensity was examined by Food Craving Questionnaires State and Trait and Food Craving Inventory before, during, (5-days) and one month (30-days) after tDCS. RESULTS: Single session of tDCS significantly reduced the intensity of current food craving (FCQ-S). Five days of active tDCS significantly reduced habitual experiences of food craving (FCQ-T), when compared to baseline pre-stimulation levels. Furthermore, both current (FCQ-S) and habitual craving (FCQ-T) were significantly reduced 30 days after active tDCS, while sham tDCS, i.e. a single tDCS session did not have significant effects. Also, active tDCS significantly decreased craving for fast food and sweets, and to a lesser degree for fat, while it did not have significant effects on craving for carbohydrates (FCI). There were no significant differences between individual FCQ-T subscales (craving dimensions) after 5 or 30 days of either sham or active tDCS. Changes in craving were not significantly associated with the initial weight, or with weight changes 30 days after the stimulation in the subjects. CONCLUSIONS: The results confirm earlier findings that single session of tDCS has immediate effects in reducing food craving. They also show that repeated tDCS over the right DLPFC may increase the duration of its effects, which may be present 30 days after the stimulation. These results support further investigation of the use of tDCS in obesity.
Asunto(s)
Ansia/fisiología , Sobrepeso/terapia , Corteza Prefrontal/fisiología , Estimulación Transcraneal de Corriente Directa/métodos , Adulto , Femenino , Humanos , Masculino , Sobrepeso/fisiopatología , Corteza Prefrontal/fisiopatología , Adulto JovenRESUMEN
Deep-brain stimulation at high frequencies (HFS) directed to the subthalamic nucleus (STN) is used increasingly to treat patients with Parkinson's disease. However, the mechanism of action by which HFS of the STN achieves its therapeutic effects remains unresolved. Insofar as lesions of the STN have similar therapeutic benefit, a favored hypothesis is that HFS acts by suppressing neural activity in the STN. The purpose of the present study was to exploit prior observations that exposure to ether anesthesia in a rodent model evokes c-fos expression (a marker of neural activation) in the STN and its efferent structures, the globus pallidus, entopeduncular nucleus and substantia nigra. We showed first that exposure to ether induced a profound oscillatory pattern of neural activity in the STN and SNr, which could explain the marked induction of c-fos immunoreactivity in these structures. Secondly, inhibition of the STN by local injections of the GABA agonist, muscimol, suppressed ether-evoked c-fos expression in all target structures. This showed that excitation of target structures in the ether model originated, at least in part, from the STN. Thirdly, and contrary to expectation, HFS of the STN increased further the expression of c-fos in the STN target structures of animals treated with ether. Finally, we demonstrated, in the absence of ether treatment, that HFS and chemical stimulation of the STN with local injections of kainic acid both induced c-fos expression in the globus pallidus, entopeduncular nucleus and substantia nigra. Together these results suggest that the principal action of STN stimulation at high frequencies is to excite rather than inhibit its efferent targets. Given that Parkinsonism has been associated with increased levels of inhibitory output activity from the basal ganglia, it is unlikely that excitation of output structures revealed in this study provides a basis for deep-brain stimulation's therapeutic action.
Asunto(s)
Estimulación Encefálica Profunda/métodos , Neuronas/fisiología , Proteínas Proto-Oncogénicas c-fos/metabolismo , Núcleo Subtalámico/fisiología , Anestésicos por Inhalación/farmacología , Animales , Núcleo Entopeduncular/efectos de los fármacos , Núcleo Entopeduncular/fisiología , Éter/farmacología , Agonistas de Aminoácidos Excitadores/farmacología , Técnica del Anticuerpo Fluorescente , Agonistas de Receptores de GABA-A/farmacología , Globo Pálido/efectos de los fármacos , Globo Pálido/fisiología , Inmunohistoquímica , Neuroestimuladores Implantables , Ácido Kaínico/farmacología , Masculino , Microscopía Confocal , Muscimol/farmacología , Vías Nerviosas/efectos de los fármacos , Vías Nerviosas/fisiología , Neuronas/efectos de los fármacos , Periodicidad , Ratas Wistar , Sustancia Negra/efectos de los fármacos , Sustancia Negra/fisiología , Núcleo Subtalámico/efectos de los fármacosRESUMEN
Although the brain's ability to change constantly in response to external and internal inputs is now well recognized the mechanisms behind it in normal aging and neurodegeneration are less well understood. To gain a better understanding, transcranial magnetic stimulation (TMS) has been used extensively to characterize non-invasively the cortical neurophysiology of the aging and degenerating brain. Furthermore, there has been a surge of studies examining whether repetitive TMS (rTMS) can be used to improve functional deficits in various conditions including normal aging, Alzheimer's and Parkinson's disease. The results of these studies in normal aging and neurodegeneration have emerged reasonably coherent in delineating the main pathology in spite of considerable technical limitations, omnipresent methodological variability, and extraordinary patient heterogeneity. Nevertheless, comparing and integrating what is known about TMS measurements of cortical excitability and plasticity in disorders that predominantly affect cortical brain structures with disorders that predominantly affect subcortical brain structures may provide better understanding of normal and abnormal brain aging fostering new. The present review provides a TMS perspective of changes in cortical neurophysiology and neurochemistry in normal aging and neurodegeneration by integrating what is revealed in individual TMS measurements of cortical excitability and plasticity in physiological aging, Alzheimer's, Parkinson's, and Huntington's, disease. The paper also reflects on current developments in utilizing TMS as a physiologic biomarker to discriminate physiologic aging from neurodegeneration and its potential as a method of therapeutic intervention.
Asunto(s)
Envejecimiento/fisiología , Enfermedad de Alzheimer/fisiopatología , Encéfalo/fisiopatología , Enfermedad de Huntington/fisiopatología , Enfermedad de Parkinson/fisiopatología , Humanos , Estimulación Magnética TranscranealRESUMEN
The aim of this study was to examine whether single-pulse transcranial magnetic stimulation (spTMS) affects the pattern of corticospinal activity once voluntary drive has been restored after spTMS-induced EMG silence. We used fractal dimension (FD) to explore the 'complexity' of the electromyography (EMG) signal, and median frequency of the spectra (MDF) to examine changes in EMG spectral characteristics. FD and MDF of the raw EMG epochs immediately before were compared with those obtained from epochs after the EMG silence. Changes in FD and MDF after spTMS were examined with three levels of muscle contraction corresponding to weak (20-40%), moderate (40-60%) and strong (60-80% of maximal voluntary contraction) and three intensities of stimulation set at 10, 20 and 30% above the resting motor threshold. FD was calculated using the Higuchi fractal dimension algorithm. Finally, to discern the origin of FD changes between the CNS and muscle, we compared the effects of spTMS with the effects of peripheral nerve stimulation (PNS) on FD and MDF. The results show that spTMS induced significant decrease in both FD and MDF of EMG signal after stimulation. PNS did not have any significant effects on FD nor MDF. Changes in TMS intensity did not have any significant effect on FD or MDF after stimulation nor had the strength of muscle contraction. However, increase in contraction strength decreased FD before stimulation but only between weak and moderate contraction. The results suggest that the effects of spTMS on corticospinal activity, underlying voluntary motor output, outlast the TMS stimulus. It appears that the complexity of the EMG signal is reduced after spTMS, suggesting that TMS alters the dynamics of the ongoing corticospinal activity most likely temporarily synchronizing the neural network activity. Further studies are needed to confirm whether observed changes after TMS occur at the cortical level.
Asunto(s)
Potenciales Evocados Motores/fisiología , Nervios Periféricos/fisiología , Estimulación Magnética Transcraneal , Adulto , Biofisica , Estimulación Eléctrica , Electromiografía , Análisis Factorial , Femenino , Humanos , Masculino , Persona de Mediana Edad , Contracción Muscular/fisiología , Músculo Esquelético/inervación , Músculo Esquelético/fisiología , Adulto JovenRESUMEN
The complex interplay between hypernatremic osmotic disturbances and cerebral lesions is yet to be clarified. In this review, we discuss, on the basis of the reported data of hypernatremic CNS challenge in the adult population, the clinical and radiologic features of the condition. Our search captured 20 case studies and 1 case series with 30 patients in total who acquired acute hypernatremia due to different etiologies and developed CNS lesions. We explored the associations between premorbid conditions, clinical presentation, hypernatremic state, correction rate, and radiologic appearance, including the localization of brain lesions and the outcomes. The results revealed that altered mental status was the most commonly reported symptom and osmotic demyelination syndrome in the form of extrapontine myelinolysis was the prevailing radiologic pattern. Finally, we contrasted, when appropriate, clinical and experimental data related to hypernatremic and hyponatremic osmotic insults to aid the understanding of the pathophysiology of CNS osmotic brain injury.
Asunto(s)
Encefalopatías/diagnóstico , Encefalopatías/etiología , Hipernatremia/complicaciones , Hipernatremia/diagnóstico , Neurorradiografía , Adulto , Enfermedades Desmielinizantes/diagnóstico , Enfermedades Desmielinizantes/etiología , Femenino , Humanos , Masculino , Estadística como Asunto , Evaluación de Síntomas/estadística & datos numéricos , Síndrome , Adulto JovenRESUMEN
OBJECTIVE: Little is known whether and how chronic exposure to dopaminergic treatment alters physiological mechanisms in Parkinson's disease (PD). METHODS: Two clinically similar groups of PD patients, one consisting of drug-naïve patients and another of patients already on chronic dopaminergic medication (when off medication), were compared to each other and to a control group. Plasticity and excitability of the hand primary motor cortex of the more affected side were evaluated using transcranial magnetic stimulation (TMS) techniques. RESULTS: There was little difference between two patient groups, and both groups showed similar differences in comparison to controls: decreased facilitatory sensory-motor plasticity (as measured by paired associative stimulation [PAS] protocol), impaired short-interval intracortical inhibition (SICI), and diminished slope of input-output curves at higher TMS intensities. The exception was that 30 min after PAS, intracortical facilitation (ICF) was significantly reduced in drug-naïve patients, whereas it changed much less in other two groups. CONCLUSIONS: Chronic exposure to dopaminergic drugs does not affect substantially the features of motor cortex excitability and plasticity in PD. There is little interaction between plasticity and excitability features of motor cortex in PD. SIGNIFICANCE: Reduced response to facilitatory PAS protocol, reduced SICI, and reduced slope of the input-output curve at higher TMS pulse intensities, seem to be physiological markers for the presence of the pathological disease process in PD. Long term treatment does not seem to change the underlying physiology of the disease.
Asunto(s)
Dopaminérgicos/farmacología , Corteza Motora/efectos de los fármacos , Plasticidad Neuronal/efectos de los fármacos , Enfermedad de Parkinson/fisiopatología , Adulto , Anciano , Antiparkinsonianos/uso terapéutico , Interpretación Estadística de Datos , Dopaminérgicos/uso terapéutico , Estimulación Eléctrica , Electromiografía , Femenino , Mano/inervación , Mano/fisiología , Humanos , Levodopa/uso terapéutico , Masculino , Persona de Mediana Edad , Contracción Muscular/fisiología , Enfermedad de Parkinson/tratamiento farmacológico , Estimulación Magnética Transcraneal , Temblor/tratamiento farmacológico , Temblor/fisiopatologíaRESUMEN
The aim of this study was to examine whether the changes of the motor cortex excitability induced by muscle fatigue could be affected by prior or subsequent intervention protocol supposed to induce opposing excitability changes. For this purpose we used paired associative stimulation (PAS) method, where peripheral nerve stimuli were associated with transcranial magnetic stimulation (TMS) of the motor cortex at a fixed interstimulus interval of 25 ms. The PAS protocol used is known to produce a long lasting, long-term potentiation (LTP) like change of cortical plasticity manifested by significant increase in motor evoked potentials (MEPs) amplitude. In this study, we confirmed significant MEP size reduction following fatigue, which had been already reported in the literature. When PAS was applied either immediately before or after muscle fatigue protocol, the excitability changes were largely occluded and MEP sizes remained close to baseline levels. However, in spite of the effects on cortical excitability, conditioning with PAS did not cause any change in target fatigue measure, the endurance point, which remained the same as when fatiguing protocol was applied alone. The present results demonstrate that fatigue-related changes in cortical excitability can be modulated by either prior or subsequent excitability promoting activity. They also suggest that muscle fatigue associated changes in motor cortical excitability probably represent non-specific activity-related plasticity, rather than a direct expression of the so-called central fatigue.
Asunto(s)
Estimulación Eléctrica/métodos , Corteza Motora/fisiología , Fatiga Muscular/fisiología , Adulto , Electromiografía/métodos , Potenciales Evocados Motores/fisiología , Femenino , Humanos , Masculino , Plasticidad Neuronal/fisiología , Nervios Periféricos/fisiología , Pulgar/fisiología , Estimulación Magnética Transcraneal/métodosRESUMEN
Diabetes mellitus is associated with a variety of cardiovascular complications including impaired cardiac muscle function. The effects of insulin treatment on heart rate, body temperature and physical activity in the alloxan (ALX)-induced diabetic rat were investigated using in vivo biotelemetry techniques. The electrocardiogram, physical activity and body temperature were recorded in vivo with a biotelemetry system for 10 days before ALX treatment, for 20 days following administration of ALX (120 mg/kg) and thereafter, for 15 days whilst rats received daily insulin. Heart rate declined rapidly after administration of ALX. Pre-ALX heart rate was 321+/-9 beats per minute, falling to 285+/-12 beats per minute 15-20 days after ALX and recovering to 331+/-10 beats per minute 5-10 days after commencement of insulin. Heart rate variability declined and PQ, QRS and QT intervals were prolonged after administration of ALX. Physical activity and body temperature declined after administration of ALX. Pre-ALX body temperature was 37.6+/-0.1 °C, falling to 37.3+/-0.1 °C 15-20 days after ALX and recovering to 37.8+/-0.1 °C 5-10 days after commencement insulin. ALX-induced diabetes is associated with disturbances in heart rhythm, physical activity and body temperature that are variously affected during insulin treatment.
Asunto(s)
Temperatura Corporal/efectos de los fármacos , Diabetes Mellitus Experimental/fisiopatología , Frecuencia Cardíaca/efectos de los fármacos , Hipoglucemiantes/farmacología , Insulina/farmacología , Aloxano/administración & dosificación , Aloxano/farmacología , Animales , Glucemia , Diabetes Mellitus Experimental/metabolismo , Hipoglucemiantes/administración & dosificación , Insulina/administración & dosificación , Masculino , Actividad Motora/efectos de los fármacos , Ratas , Ratas WistarRESUMEN
Extrapontine myelinolysis (EPM) and cortical laminar necrosis (CLN) have rarely been reported in association with severe hypernatremia. We describe a patient with EPM associated with CLN following severe hypernatremia due to hypertonic peritoneal lavage after a ruptured hydatid cyst of the liver. Clinical and neuroimaging findings in acute stage and serial brain MRI at two and five month follow-up are discussed in detail.
RESUMEN
Diabetes induces changes in the structural, biochemical, electrical, and contractile properties of skeletal muscles. Neuropeptide Y (NPY) administered locally can induce angiogenesis in a rat ischemic limb model and restore the contractile function of the ischemic muscle. The effects of NPY on the contractile characteristics of limb skeletal muscles were examined in streptozotocin-induced diabetic rats. Rats were treated with sham pellets (control groups) or NPY-containing pellets (1 mg of NPY/pellet, 14 days releasing time) administered locally to the rat hind limb 2 months after induction of diabetes. Contractile properties and fatigability of the slow-twitch soleus and fast-twitch gastrocnemius medials muscle were compared in control (sham), control NPY, diabetic (sham), and diabetic NPY groups. In order to induce fatigue trains of repetitive tetanic stimulation were used (600 ms/1 s simulation-rest cycle per train, 112 trains at an 85-Hz fusion frequency). Two months of untreated diabetes significantly prolonged soleus contraction and slowed its relaxation, but had minimal effects on soleus tension. NPY ameliorated the diabetic effects on soleus speed-related contractile properties, restoring its contraction and relaxation times. Diabetes significantly reduced gastrocnemius medials tetanic tension, leaving its contractile characteristics mostly unaffected. NPY partially restored gastrocnemius tetanic tension production capacity. Diabetes significantly increased fatigability of both muscles, which was partially restored by NPY, as evidenced by restored endurance of soleus muscle. The results suggest that NPY administered locally tends to normalize muscle performance and improve fatigue resistance of skeletal muscles in streptozotocin diabetes. Further examination is needed to establish the mechanisms of local NPY action on muscle contractile properties in streptozotocin-induced diabetes.
Asunto(s)
Diabetes Mellitus Experimental/fisiopatología , Contracción Muscular/efectos de los fármacos , Neuropéptido Y/farmacología , Animales , Masculino , Fatiga Muscular/efectos de los fármacos , Fibras Musculares de Contracción Rápida , Fibras Musculares de Contracción Lenta , Neuropéptido Y/uso terapéutico , Ratas , Ratas WistarRESUMEN
Streptozotocin (STZ) and alloxan (ALX) are widely used to induce diabetes mellitus in experimental animals. The direct effects of STZ and ALX on the amplitude and time course of ventricular myocyte shortening and on cardiac action potentials were investigated. STZ and ALX (10(-5)M) were dissolved in normal Tyrode (NT), maintained at pH 7.4 and 37 degrees C and stored for either 15 or 60-120min. Both compounds reduced the amplitude of myocyte shortening. Compared to NT the amplitude of shortening was 34.7+/-5.0% and 35.2+/-6.8% with STZ and 41.0+/-5.5% and 37.3+/-5.7% with ALX stored for 15 and 60-120min, respectively. During a 10min NT washout STZ myocytes recovered to 56.2+/-8.3% and 60.5+/-8.2% and ALX myocytes recovered to 88.9+/-10.0% and 83.7+/-9.9% after storage of compounds for 15 and 60-120min, respectively. Perfusion of the whole heart with ALX induced bradycardia but had no effects on the duration of action potential repolarization at 50% and 70% from peak action potential. The negative inotropic effects of STZ and ALX were not altered by storage. The results suggest that some of the effects on heart reported in STZ- and ALX-induced diabetes may be partly attributed to direct action of these compounds.
Asunto(s)
Aloxano/farmacología , Contracción Miocárdica/efectos de los fármacos , Estreptozocina/farmacología , Potenciales de Acción/efectos de los fármacos , Animales , Depresión Química , Ventrículos Cardíacos/efectos de los fármacos , Concentración de Iones de Hidrógeno , Técnicas In Vitro , Masculino , Células Musculares/efectos de los fármacos , Ratas , Ratas Wistar , Temperatura , Factores de TiempoRESUMEN
We have investigated the effects of changing the coil-to-skull distance on the motor-evoked responses (MEP) induced with two different magnetic stimulator coils (80 mm round and figure-of-eight coil) at rest and during voluntary muscle contraction. The changes in MEP latency, amplitude and silent period (SP) duration induced by stimulation directly upon the skull, and 1 cm away from the skull were analyzed by computing the probability density distribution (PDD) for the responses obtained from all subjects. This measure corresponds to the finite probability that the event occurs within a given area. Overall, the results were consistent with a distance-induced decrease in magnetic field strength. However, the increase in coil-to-skull distance induced a higher probability of longer latencies in active muscle when stimulating with either coil. Also, stimulating at a distance with the figure-of-eight coil increased the probability of a longer SP duration. The stimulation strength at the two distances was comparable because it was set based on the motor threshold obtained for each distance. Therefore, our results are not entirely compatible with the established exponential drop in magnetic field with increasing distance. Rather, they suggest that a more complex set of interactions occurs in the cortex. The results imply that distinct patterns of cortical network activation may exist related to the distance-induced alterations when the coil is moved away from the skull. Further studies are required to elucidate the precise nature of the distance-related interactions of the magnetic field with the cortex.
Asunto(s)
Potenciales Evocados Motores/fisiología , Corteza Motora/fisiología , Cráneo/anatomía & histología , Estimulación Magnética Transcraneal/instrumentación , Estimulación Magnética Transcraneal/métodos , Adulto , Femenino , Mano/inervación , Mano/fisiología , Humanos , Masculino , Corteza Motora/anatomía & histología , Contracción Muscular/fisiología , Músculo Esquelético/inervación , Músculo Esquelético/fisiología , Conducción Nerviosa/fisiología , Tractos Piramidales/fisiología , Tiempo de Reacción/fisiología , Factores de TiempoRESUMEN
This study examined the influence of two intensities of exercise on ventricular myocyte shortening and intracellular calcium in the streptozotocin (STZ)-induced diabetic rat. Animals were divided into four groups: control sedentary (CS), diabetic sedentary (DS), diabetic light exercise (DLE; 5 x 30 min/week, 9 m/min) and diabetic moderate exercise (DME; 5 x 30 min/week, 18 m/min) and the exercise programme started 2 months after STZ treatment. Time to peak (TPK) shortening was prolonged in myocytes from DS (112.1 +/- 2.5 ms) compared to CS (98.1 +/- 2.1 ms) rats and was not additionally altered by either light (117.0 +/- 2.1 ms) or moderate (115.4 +/- 2.0 ms) exercise. TPK of the Ca(2+) transient was not significantly altered by STZ treatment (69.4 +/- 2.4 ms) but was prolonged by light (79.8 +/- 3.5 ms) and moderate (76.6 +/- 2.9 ms) exercise compared to CS (65.5 +/- 2.7 ms). Data from this study suggest that the chosen intensities of exercise were ineffective in modulating the dynamics of cardiac muscle contraction and reversing the deleterious effects of diabetes on heart-muscle contraction.
Asunto(s)
Calcio/metabolismo , Diabetes Mellitus Experimental/fisiopatología , Ventrículos Cardíacos/citología , Espacio Intracelular/metabolismo , Contracción Miocárdica , Miocitos Cardíacos/metabolismo , Condicionamiento Físico Animal , Animales , Glucemia/metabolismo , Peso Corporal/efectos de los fármacos , Cafeína/farmacología , Señalización del Calcio/efectos de los fármacos , Estimulación Eléctrica , Espacio Intracelular/efectos de los fármacos , Contracción Miocárdica/efectos de los fármacos , Miocitos Cardíacos/efectos de los fármacos , Ratas , Ratas Wistar , Retículo Sarcoplasmático/efectos de los fármacos , Retículo Sarcoplasmático/metabolismo , EstreptozocinaRESUMEN
Recently, it has been shown that the subthalamic nucleus (STN) has anticonvulsant effects on epileptic seizures originating from the forebrain. The aim of the present study was to determine whether the anticonvulsant properties of the STN extend to the suppression of tonic seizures originating from the brainstem elicited by electroshock in rats. Three different procedures were used to manipulate activity in the STN and in each case the duration of tonic hindlimb extension elicited by electroshock was used as a measure of seizure-severity. Under general anesthesia, two groups of rats received chronic implants of either bilateral stainless steel guide cannulae or bilateral bipolar stimulating electrodes stereotaxically implanted and aimed at the STN. After 3 days of recovery, each rat in the first group was tested with electroshock on three consecutive days after having received 220 nl bilateral microinjections into the STN of either 200 or 400 pmol of muscimol (a GABA agonist) dissolved in saline or the same volume of normal saline. In the second group the electroshock test was conducted, again on three consecutive days, immediately following high frequency electrical stimulation (HFS) of the STN at 130 or 260 Hz or a no current control condition. In the third group, rats were tested with electroshock before and after bilateral excitotoxic lesions of the STN with either kainic or ibotenic acids. None of these manipulations produced significant suppression of the tonic hind limb extension elicited by electroshock compared with the relevant control conditions. This suggests that, within the limitations of the current procedures, the anticonvulsant properties of the STN appear to be ineffective against tonic seizures originating in the brainstem.
Asunto(s)
Epilepsia Generalizada/fisiopatología , Núcleo Subtalámico/fisiología , Animales , Conducta Animal/efectos de los fármacos , Conducta Animal/fisiología , Estimulación Eléctrica , Electrodos Implantados , Electrochoque , Femenino , Agonistas del GABA/administración & dosificación , Agonistas del GABA/farmacología , Inmunohistoquímica , Masculino , Microinyecciones , Muscimol/administración & dosificación , Muscimol/farmacología , Proteínas Proto-Oncogénicas c-fos/biosíntesis , Ratas , Ratas Wistar , Convulsiones/fisiopatología , Núcleo Subtalámico/efectos de los fármacosRESUMEN
The information transmission properties of ensembles of MSs and the effect of the gamma system on these properties were studied. Three converging lines of research were taken: (1) the development of information theoretic estimation tools, and the formulation of an "operational" interpretation for the information rate; (2) animal experiments in which the mutual information rate was estimated and the effect of the gamma system was quantified; (3) simulation of a muscle spindle model with gamma activation in order to corroborate the results of the animal experiments. The main hypothesis was that the gamma system will enhance information theoretic measures that quantify the quality of the sensory neural channel comprised from an ensemble of primary muscle spindle afferents. A random stimulus was applied to a muscle in the hind limb of a cat, while spike trains from several primary MS afferents were recorded simultaneously. The stimulus was administered twice, with an operative and a disconnected gamma system. The mutual information rate between the stimulus and spike trains, as well as other information theoretic measures, was estimated. The information rate of ensembles of MSs increased with increasing ensemble size. However, with an operative gamma system the "ensemble effect" was much higher. In addition, the ensemble effect was influenced by the stimulus spectrum. A muscle spindle population model with gamma activation was simulated with stimuli that were identical to that of the animal experiments. The simulation results supported the experimental results and corroborated the main hypothesis. The results indicate that the gamma system has an important role in enhancing information transmission from ensembles of MSs to the spinal cord.
Asunto(s)
Potenciales de Acción/fisiología , Neuronas Motoras gamma/fisiología , Husos Musculares/fisiología , Músculo Esquelético/inervación , Neuronas Aferentes/fisiología , Reflejo de Estiramiento/fisiología , Algoritmos , Animales , Gatos , Estimulación Eléctrica , Modelos Neurológicos , Músculo Esquelético/fisiología , Conducción Nerviosa/fisiología , Médula Espinal/citología , Médula Espinal/fisiología , Raíces Nerviosas Espinales/fisiología , Transmisión Sináptica/fisiologíaRESUMEN
The present work was designed to check for the possibility of interactions between mechanical innocuous and chemically induced noxious muscle afferent inputs on discharge behavior of nociceptive superficial dorsal horn neurons (SDHNs) of the spinal cord in decerebrated cats. The innocuous and noxious stimuli were applied separately and in combination, so that the effects of the innocuous stimulus on nociceptive processing could be evaluated. The innocuous stimulus consisted of ramp-and-hold stretches of the gastrocnemius muscles, whereas the noxious stimulus consisted of i.a. injections of bradykinin (BK; 0.5-1 ml, 50 microg/ml) into the arterial circulation of same muscles. Only neurons up to approximately 1mm depth and those that responded to noxious pinch of the gastrocnemius muscles were selected for further analysis. The activity of 16 dorsal horn neurons was recorded extracellularly with high-impedance glass microelectrodes, out of which seven responded to stretch, while 12 neurons responded to bradykinin injections. The bradykinin injections induced three types of responses: excitatory, inhibitory and mixed. The majority of the neurons that showed excitatory and mixed responses to bradykinin were also influenced by stretches applied directly after the bradykinin injection. In these neurons, the stretch usually counteracted the bradykinin-induced response, i.e. shortening and reducing bradykinin-induced excitation and re-exciting the cells after bradykinin-induced inhibition. The mechanism of the stretch modulation is proposed to reside in a segmental spinal control of the nociceptive transmission.
Asunto(s)
Potenciales de Acción/fisiología , Contracción Muscular/fisiología , Husos Musculares/fisiología , Músculo Esquelético/fisiología , Células del Asta Posterior/fisiología , Potenciales de Acción/efectos de los fármacos , Animales , Bradiquinina/farmacología , Gatos , Contracción Muscular/efectos de los fármacos , Husos Musculares/efectos de los fármacos , Músculo Esquelético/efectos de los fármacos , Estimulación Física/métodos , Células del Asta Posterior/efectos de los fármacos , Estimulación QuímicaRESUMEN
The information transmission properties of single, de-efferented primary muscle-spindle afferents from the hind limb of the cat were investigated. The gastrocnemius medialis muscle was stretched randomly while recording spike trains from several muscle-spindle afferents in the dorsal root. Two classes of input stimuli were used: (i) Gaussian noise with band-limited flat spectrum, and (ii) Gaussian noise with a more "naturalistic" 1/f(n) spectrum. The "reconstruction" method was used to calculate a lower bound to the information rate (in bits per second) between the muscle spindles and the spinal cord. Results show that in response to the flat-spectrum input, primary muscle-spindle afferents transfer information mainly about high frequencies, carrying 2.12 bits/spike. In response to naturalistic-spectrum inputs, primary muscle-spindle afferents transfer information about both low and high frequencies, with "spiking efficiency" increasing to 2.67 bits/spike. A simple muscle-spindle simulation model was analyzed with the same method, emphasizing the important part played by the intrafusal fiber mechanical properties in information transmission.
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Vías Aferentes/fisiología , Husos Musculares/fisiología , Músculo Esquelético/inervación , Neuronas Aferentes/fisiología , Potenciales de Acción/fisiología , Vías Aferentes/citología , Animales , Gatos , Estimulación Eléctrica , Mecanotransducción Celular/fisiología , Modelos Neurológicos , Neuronas Motoras gamma/fisiología , Contracción Muscular/fisiología , Husos Musculares/citología , Músculo Esquelético/fisiología , Neuronas Aferentes/citología , Distribución Normal , Raíces Nerviosas Espinales/citología , Raíces Nerviosas Espinales/fisiologíaRESUMEN
In the medial gastrocnemius muscle of the decerebrate cat, the spatial spread of fatigue between active and inactive muscle parts was studied. Conditioning fatiguing stimulation (CFS) was applied to a part of the muscle to test whether it had an effect on the contraction efficiency in an unstimulated part. To exclude somato-sympathetic reflexes during CFS, a full rhizotomy of the lumbo-sacral spinal cord was performed. The same ipsilateral ventral root, either L7 or S1, was divided into seven filaments, one of which was used for the test stimulation, and four or five for CFS. The CFS consisted of 12 s sessions of distributed stimulation of five (or four) filaments at a rate of 40 s(-1), the sessions were repeated, every 40 s, 15 or more times. The test consisted of 12 s of regular stimulation at a rate of 10 s(-1), preceded and followed by a single stimulus. The tests applied just after CFS showed a strong decline of both tension and electromyogram (EMG), amounting to only [mean (SD)] 0.45 (0.18) and 0.51 (0.19) (n = 15), respectively, of the corresponding values in the tests before CFS. It thus turned out that depressive fatigue-related effects could spread within the muscle. At the same time, control reactions recorded in the lateral gastrocnemius during stimulation of its cut nerve did not change. Subsequent repetitions of the tests usually revealed a tendency towards restoration. The EMG reactions recovered more quickly than tension. The depression of EMG after CFS was accompanied by a slowing of the constituent M-waves; their latencies decreased during restoration. Distinct changes in the systemic blood pressure were observed during CFS. These changes were usually correlated well with muscle tension changes. The factors possibly underlying the observed effects may include diffusion of metabolites from active to inactive muscle fibres, lowering of the efficiency of neuro-muscular transmission due to squeezing of efferent motor terminals and changes in outer metabolite content, as well as local hypoxia due to increases in intramuscular pressure.
Asunto(s)
Fatiga Muscular/fisiología , Músculo Esquelético/fisiología , Animales , Presión Sanguínea/fisiología , Gatos , Estimulación Eléctrica , Electromiografía , Femenino , Isquemia/fisiopatología , Contracción Isométrica/fisiología , Masculino , Músculo Esquelético/inervación , Sistema Nervioso Simpático/fisiologíaRESUMEN
Previous reports showed that sympathetic stimulation affects the activity of muscle spindle afferents (MSAs). The aim of the present work is to study the characteristics of sympathetic modulation of MSA response to stretch: (i) on the dynamic and static components of the stretch response, and (ii) on group Ia and II MSAs to evaluate potentially different effects. In anaesthetised rabbits, the peripheral stump of the cervical sympathetic nerve (CSN) was stimulated at 10 impulses s(-1) for 45-90 s. The responses of single MSAs to trapezoidal displacement of the mandible were recorded from the mesencephalic trigeminal nucleus. The following characteristic parameters were determined from averaged trapezoidal responses: initial frequency (IF), peak frequency at the end of the ramp (PF), and static index (SI). From these, other parameters were derived: dynamic index (DI = PF - SI), dynamic difference (DD = PF - IF) and static difference (SD = SI - IF). The effects of CSN stimulation were also evaluated during changes in the state of intrafusal muscle fibre contraction induced by succinylcholine and curare. In a population of 124 MSAs, 106 units (85.4 %) were affected by sympathetic stimulation. In general, while changes in resting discharge varied among different units (Ia vs. II) and experimental conditions (curarised vs. non-curarised), ranging from enhancement to strong depression of firing, the amplitude of the response to muscle stretches consistently decreased. This was confirmed and detailed in a quantitative analysis performed on 49 muscle spindle afferents. In both the non-curarised (23 units) and curarised (26 units) condition, stimulation of the CSN reduced the response amplitude in terms of DD and SD, but hardly affected DI. The effects were equally present in both Ia and II units; they were shown to be independent from gamma drive and intrafusal muscle tone and not secondary to muscle hypoxia. Sympathetic action on the resting discharge (IF) was less consistent. In the non-curarised condition, IF decreased in most Ia units, while in II units decreases and increases occurred equally often. In the curarised condition, IF in group II units mostly increased. The results have important functional implications on the control of motor function in a state of 'high' sympathetic activity, like excessive stress, as well as in certain pathological conditions such as sympathetically maintained pain.
Asunto(s)
Maxilares/fisiología , Músculo Masetero/inervación , Músculo Masetero/fisiología , Husos Musculares/fisiología , Sistema Nervioso Simpático/fisiología , Animales , Curare/farmacología , Estimulación Eléctrica , Músculo Masetero/irrigación sanguínea , Husos Musculares/efectos de los fármacos , Fármacos Neuromusculares Despolarizantes/farmacología , Fármacos Neuromusculares no Despolarizantes/farmacología , Neuronas Aferentes/fisiología , Conejos , Succinilcolina/farmacologíaRESUMEN
The distribution of Fos-immunoreactive (Fos-ir) and nicotinamide adenine dinucleotide phosphate-diaphorase (NADPH-d)-reactive neurons in the rat lumbar spinal cord was examined following muscle fatigue caused by intermittent high-rate (100 s(-1)) electrical stimulation of the triceps surae muscle or the ventral root L5 (VRL5) for 30 min. Following both types of stimulation, the fatigue-related c-fos gene expression was more extensive in the L2-L5 segments on the stimulated side, and the majority of Fos-ir neurons were concentrated in the dorsal horn. After direct muscle stimulation, the highest number of Fos-ir neurons were detected in two regions: layer 5, and superficial layers (1 and 2(o)), although many labeled cells were also found in layers 3, 4, 6, and 7. In response to VRL5 stimulation, the maximal density of Fos-ir neurons was detected in the middle and lateral parts of layers 1 and 2(o), the zone of termination of high-threshold muscle afferents(.) Statistically significant prevalence of Fos-ir cell number was also found in layers 5 and 7 on the stimulated side. A few Fos-ir neurons were detected in the ventral horn (layer 8 and area 10) on both sides. The lamellar distribution of NADPH-d-reactive neurons was similar over all experimental groups of animals. In the L3-L6 segments, such reactive cells were arranged in two distinct regions: dorsal horn (layers 2(i), 3, and 5) and area 10; in the L1 and L2 segments, an additional cluster of NADPH-d positive cells was found in the intermediolateral cell column (IML). Double-labeled cells were not detected. We suggest that c-fos expression in response to muscle fatigue reveals activity of functionally different types of spinal neurons which could operate together with NOS-containing cells in pre-motoneuronal networks to modulate the motoneuron output.