RESUMEN
In this work, we couple a lumped-parameter closed-loop model of the cardiovascular system with a physiologically-detailed mathematical description of the baroreflex afferent pathway. The model features a classical Hodgkin-Huxley current-type model for the baroreflex afferent limb (primary neuron) and for the second-order neuron in the central nervous system. The pulsatile arterial wall distension triggers a frequency-modulated sequence of action potentials at the afferent neuron. This signal is then integrated at the brainstem neuron model. The efferent limb, representing the sympathetic and parasympathetic nervous system, is described as a transfer function acting on heart and blood vessel model parameters in order to control arterial pressure. Three in silico experiments are shown here: a step increase in the aortic pressure to evaluate the functionality of the reflex arch, a hemorrhagic episode and an infusion simulation. Through this model, it is possible to study the biophysical dynamics of the ionic currents proposed for the afferent limb components of the baroreflex during the cardiac cycle, and the way in which currents dynamics affect the cardiovascular function. Moreover, this system can be further developed to study in detail each baroreflex loop component, helping to unveil the mechanisms involved in the cardiovascular afferent information processing.
Asunto(s)
Vías Aferentes , Barorreflejo , Simulación por Computador , Barorreflejo/fisiología , Humanos , Vías Aferentes/fisiología , Modelos Cardiovasculares , Potenciales de Acción/fisiología , Neuronas Aferentes/fisiologíaRESUMEN
Mechanosensory neurons located across the body surface respond to tactile stimuli and elicit diverse behavioral responses, from relatively simple stimulus location-aimed movements to complex movement sequences. How mechanosensory neurons and their postsynaptic circuits influence such diverse behaviors remains unclear. We previously discovered that Drosophila perform a body location-prioritized grooming sequence when mechanosensory neurons at different locations on the head and body are simultaneously stimulated by dust (Hampel et al., 2017; Seeds et al., 2014). Here, we identify nearly all mechanosensory neurons on the Drosophila head that individually elicit aimed grooming of specific head locations, while collectively eliciting a whole head grooming sequence. Different tracing methods were used to reconstruct the projections of these neurons from different locations on the head to their distinct arborizations in the brain. This provides the first synaptic resolution somatotopic map of a head, and defines the parallel-projecting mechanosensory pathways that elicit head grooming.
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Drosophila , Neuronas , Animales , Aseo Animal/fisiología , Vías Aferentes , Neuronas/fisiología , Encéfalo , Drosophila melanogaster/fisiologíaRESUMEN
Resumen La hiperacusia se define como la intolerancia a ciertos sonidos cotidianos que causa angustia y discapacidad significativas en las actividades sociales, ocupacionales, recreativas y otras actividades cotidianas. Los sonidos pueden percibirse como incómodamente fuertes, desagradables, atemorizantes o dolorosos. Se encuentra presente en aproximadamente un 3% población general, y aumenta significativamente en trastornos del espectro autista (TEA), alcanzando entre un 15% a 40%. Los mecanismos fisiopatológicos no son del todo claros, pero se ha propuesto, una alteración en el funcionamiento de mecanismos reflejos y de regulación, tanto a nivel de la vía auditiva periférica, como central, incluyendo estructuras no relacionadas directamente con la vía auditiva. El siguiente texto tiene como objetivo analizar la relación entre hiperacusia y TEA, enfatizando en la frecuencia en que se presentan como comorbilidades, en los posibles mecanismos fisiopatológicos, y en actualizaciones en el abordaje diagnóstico y terapéutico. Se realiza una revisión bibliográfica cualitativa en Pubmed con artículos entre los años 2008-2020 utilizando los términos: "hyperacusis autism", "sistema olivococlear", arrojando 39 artículos, de los cuales se seleccionaron en base a la temática de cada uno, evaluada por los autores. A pesar de una significativa relación entre hiperacusia y TEA, los mecanismos fisiopatológicos de ambas patologías siguen siendo un misterio. Existen estudios que sugieren pruebas de screening no invasivas que relacionan ambas patologías, pero debido a los sesgos de selección, todavía no son factibles de usar en forma universal. El abordaje terapéutico ha sido poco explorado, y no se dispone de fármacos que hayan demostrado su efectividad, por el contrario, algunos de ellos empeoran la sintomatología. Se recomienda al tratante, seguir un camino largo, en conjunto con el paciente, donde las terapias no farmacológicas como la terapia cognitivo conductual han mostrado tener buenos resultados.
Abstract Hyperacusis is defined as intolerance to certain sounds that causes significant distress and disability in social, occupational, recreational and other activities. Sounds can be perceived as uncomfortably loud, unpleasant, frightening, or painful. It is present in approximately 3% of the general population, and increases significantly in autism spectrum disorders (ASD), between 15% and 40%. The pathophysiological mechanisms are not entirely clear, but an alteration in the functioning of reflex and regulatory mechanisms has been proposed, both at the peripheral and central auditory pathways, including structures not directly related to the auditory pathway. The therapeutic approach has been little explored as there are no drugs that have demonstrated their effectiveness, on the contrary, some of them worsen the symptoms. The practitioner is recommended to follow a long path, in conjunction with the patient, where non-pharmacological therapies such as cognitive behavioral therapy have been shown to have good results. The following text shows a review of the literature with articles referring to the subject between the years 2008-2019.
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Humanos , Hiperacusia/epidemiología , Trastorno del Espectro Autista/complicaciones , Hiperacusia/etiología , Vías Auditivas , Vías Aferentes , Vías EferentesRESUMEN
The dorsal ventricular ridge (DVR), which is the largest component of the avian pallium, contains discrete partitions receiving tectovisual, auditory, and trigeminal ascending projections. Recent studies have shown that the auditory and the tectovisual regions can be regarded as complexes composed of three highly interconnected layers: an internal senso-recipient one, an intermediate afferent/efferent one, and a more external re-entrant one. Cells located in homotopic positions in each of these layers are reciprocally linked by an interlaminar loop of axonal processes, forming columnar-like local circuits. Whether this type of organization also extends to the trigemino-recipient DVR is, at present, not known. This question is of interest, since afferents forming this sensory pathway, exceptional among amniotes, are not thalamic but rhombencephalic in origin. We investigated this question by placing minute injections of neural tracers into selected locations of vital slices of the chicken telencephalon. We found that neurons of the trigemino-recipient nucleus basorostralis pallii (Bas) establish reciprocal, columnar and homotopical projections with cells located in the overlying ventral mesopallium (MV). "Column-forming" axons originated in B and MV terminate also in the intermediate strip, the fronto-trigeminal nidopallium (NFT), in a restricted manner. We also found that the NFT and an internal partition of B originate substantial, coarse-topographic projections to the underlying portion of the lateral striatum. We conclude that all sensory areas of the DVR are organized according to a common neuroarchitectonic motif, which bears a striking resemblance to that of the radial/laminar intrinsic circuits of the sensory cortices of mammals.
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Pollos/fisiología , Red Nerviosa/anatomía & histología , Red Nerviosa/fisiología , Núcleos del Trigémino/anatomía & histología , Núcleos del Trigémino/fisiología , Vías Aferentes/fisiología , Animales , Axones/fisiología , Mapeo Encefálico , Femenino , Inmunohistoquímica , Masculino , Neostriado/anatomía & histología , Neostriado/fisiología , Vías Nerviosas/fisiología , Sensación/fisiologíaRESUMEN
Entorhinal cortex lesions have been established as a model for hippocampal deafferentation and have provided valuable information about the mechanisms of synapse reorganization and plasticity. Although several molecules have been proposed to contribute to these processes, the role of Wnt signaling components has not been explored, despite the critical roles that Wnt molecules play in the formation and maintenance of neuronal and synaptic structure and function in the adult brain. In this work, we assessed the reorganization process of the dentate gyrus (DG) at 1, 3, 7, and 30 days after an excitotoxic lesion in layer II of the entorhinal cortex. We found that cholinergic fibers sprouted into the outer molecular layer of the DG and revealed an increase of the developmental regulated MAP2C isoform 7 days after lesion. These structural changes were accompanied by the differential regulation of the Wnt signaling components Wnt7a, Wnt5a, Dkk1, and Sfrp1 over time. The progressive increase in the downstream Wnt-regulated elements, active-ß-catenin, and cyclin D1 suggested the activation of the canonical Wnt pathway beginning on day 7 after lesion, which correlates with the structural adaptations observed in the DG. These findings suggest the important role of Wnt signaling in the reorganization processes after brain lesion and indicate the modulation of this pathway as an interesting target for neuronal tissue regeneration.
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Corteza Entorrinal/patología , Hipocampo/metabolismo , Vía de Señalización Wnt , Vías Aferentes/metabolismo , Animales , Colina/metabolismo , Masculino , Proteínas Asociadas a Microtúbulos/metabolismo , Modelos Biológicos , Fibras Nerviosas/metabolismo , Isoformas de Proteínas/metabolismo , Ratas Wistar , Proteínas Wnt/metabolismoRESUMEN
Elevated sympathetic vasomotor activity is a common feature of cardiorenal diseases. Therefore, the sympathetic nervous system is an important therapeutic target, particularly the fibers innervating the kidneys. In fact, renal denervation has been applied clinically and shown promising results in patients with hypertension and chronic kidney disease. However, the underlying mechanisms involved in the cardiorenal protection induced by renal denervation have not yet been fully clarified. This mini-review highlights historical and recent aspects related to the role of renal sensory fibers in the control of cardiorenal function under normal conditions and in experimental models of cardiovascular disease. Results have demonstrated that alterations in renal sensory function participate in the maintenance of elevated sympathetic vasomotor activity and cardiorenal changes; as such, renal sensory fibers may be a potential therapeutic target for the treatment of cardiorenal diseases. Although it has not yet been applied in clinical practice, selective afferent renal denervation may be promising, since such an approach maintains efferent activity and can provide more refined control of renal function compared with total renal denervation. However, more studies are needed to understand the mechanisms by which renal afferents partially contribute to such changes, in addition to the need to evaluate the safety and advantages of the approach for application in the clinical practice.
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Vías Aferentes/fisiopatología , Síndrome Cardiorrenal/fisiopatología , Hipertensión Renovascular/fisiopatología , Riñón/inervación , Insuficiencia Renal Crónica/fisiopatología , Sistema Nervioso Simpático/fisiopatología , Vías Aferentes/cirugía , Animales , Síndrome Cardiorrenal/cirugía , Humanos , Hipertensión Renovascular/cirugía , Insuficiencia Renal Crónica/cirugía , Simpatectomía , Sistema Nervioso Simpático/cirugíaRESUMEN
A general agreement in psycholinguistics claims that syntax and meaning are unified precisely and very quickly during online sentence processing. Although several theories have advanced arguments regarding the neurocomputational bases of this phenomenon, we argue that these theories could potentially benefit by including neurophysiological data concerning cortical dynamics constraints in brain tissue. In addition, some theories promote the integration of complex optimization methods in neural tissue. In this paper we attempt to fill these gaps introducing a computational model inspired in the dynamics of cortical tissue. In our modeling approach, proximal afferent dendrites produce stochastic cellular activations, while distal dendritic branches-on the other hand-contribute independently to somatic depolarization by means of dendritic spikes, and finally, prediction failures produce massive firing events preventing formation of sparse distributed representations. The model presented in this paper combines semantic and coarse-grained syntactic constraints for each word in a sentence context until grammatically related word function discrimination emerges spontaneously by the sole correlation of lexical information from different sources without applying complex optimization methods. By means of support vector machine techniques, we show that the sparse activation features returned by our approach are well suited-bootstrapping from the features returned by Word Embedding mechanisms-to accomplish grammatical function classification of individual words in a sentence. In this way we develop a biologically guided computational explanation for linguistically relevant unification processes in cortex which connects psycholinguistics to neurobiological accounts of language. We also claim that the computational hypotheses established in this research could foster future work on biologically-inspired learning algorithms for natural language processing applications.
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Vías Aferentes/fisiología , Simulación por Computador , Lingüística/métodos , Neocórtex/fisiología , Red Nerviosa/fisiología , Percepción del Habla/fisiología , Dendritas/fisiología , HumanosRESUMEN
The ablation of renal nerves, by destroying both the sympathetic and afferent fibers, has been shown to be effective in lowering blood pressure in resistant hypertensive patients. However, experimental studies have reported that the removal of sympathetic fibers may lead to side effects, such as the impairment of compensatory cardiorenal responses during a hemodynamic challenge. In the present study, we evaluated the effects of the selective removal of renal afferent fibers on arterial hypertension, renal sympathetic nerve activity, and renal changes in a model of renovascular hypertension. After 4 weeks of clipping the left renal artery, afferent renal denervation (ARD) was performed by exposing the left renal nerve to a 33 mM capsaicin solution for 15 min. After 2 weeks of ARD, we found reduced MAP (~ 18%) and sympathoexcitation to both the ischemic and contralateral kidneys in the hypertensive group. Moreover, a reduction in reactive oxygen species was observed in the ischemic (76%) and contralateral (27%) kidneys in the 2K1C group. In addition, ARD normalized renal function markers and proteinuria and podocin in the contralateral kidney. Taken altogether, we show that the selective removal of afferent fibers is an effective method to reduce MAP and improve renal changes without compromising the function of renal sympathetic fibers in the 2K1C model. Renal afferent nerves may be a new target in neurogenic hypertension and renal dysfunction.
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Vías Aferentes/fisiopatología , Hipertensión Renovascular/fisiopatología , Isquemia/fisiopatología , Enfermedades Renales/fisiopatología , Riñón/fisiopatología , Animales , Barorreflejo/fisiología , Presión Sanguínea/fisiología , Masculino , Núcleo Hipotalámico Paraventricular/fisiopatología , Ratas , Ratas Wistar , Sistema Nervioso Simpático/fisiopatologíaRESUMEN
The exercise pressor reflex (EPR) is engaged upon the activation of group III/IV skeletal muscle afferents and is one of the principal mediators of cardiovascular responses to exercise. This review explores the hypothesis that afferent signals from EPR communicate via GABAergic contacts within the brain stem to evoke parasympathetic withdrawal and sympathoexcitation to increase cardiac output, peripheral resistance, and blood pressure during exercise.
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Vías Aferentes/fisiología , Fenómenos Fisiológicos Cardiovasculares , Ejercicio Físico/fisiología , Neuronas GABAérgicas/fisiología , Músculo Esquelético/inervación , Núcleo Solitario/fisiología , Animales , Presión Sanguínea/fisiología , Gasto Cardíaco/fisiología , Humanos , Sistema Nervioso Simpático/fisiología , Resistencia Vascular/fisiologíaRESUMEN
Electrical stimulation of the vagus nerve (VNS) is a novel strategy used to treat inflammatory conditions. Therapeutic VNS activates both efferent and afferent fibers; however, the effects attributable to vagal afferent stimulation are unclear. Here, we tested if selective activation of afferent fibers in the abdominal vagus suppresses systemic inflammation. In urethane-anesthetized rats challenged with lipopolysaccharide (LPS, 60⯵g/kg, i.v.), abdominal afferent VNS (2 Hz for 20â¯min) reduced plasma tumor necrosis factor alpha (TNF) levels 90â¯min later by 88% compared with unmanipulated animals. Pre-cutting the cervical vagi blocked this anti-inflammatory action. Interestingly, the surgical procedure to expose and prepare the abdominal vagus for afferent stimulation ('vagal manipulation') also had an anti-inflammatory action. Levels of the anti-inflammatory cytokine IL-10 were inversely related to those of TNF. Prior bilateral section of the splanchnic sympathetic nerves reversed the anti-inflammatory actions of afferent VNS and vagal manipulation. Sympathetic efferent activity in the splanchnic nerve was shown to respond reflexly to abdominal vagal afferent stimulation. These data demonstrate that experimentally activating abdominal vagal afferent fibers suppresses systemic inflammation, and that the efferent neural pathway for this action is in the splanchnic sympathetic nerves.
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Inflamación/metabolismo , Nervios Esplácnicos/fisiología , Nervio Vago/fisiología , Abdomen/inervación , Vías Aferentes/metabolismo , Vías Aferentes/fisiología , Animales , Antiinflamatorios/farmacología , Citocinas , Modelos Animales de Enfermedad , Inflamación/inmunología , Interleucina-10/análisis , Interleucina-10/sangre , Lipopolisacáridos/farmacología , Masculino , Vías Nerviosas , Ratas , Ratas Sprague-Dawley , Nervios Esplácnicos/inmunología , Sistema Nervioso Simpático , Factor de Necrosis Tumoral alfa/análisis , Factor de Necrosis Tumoral alfa/sangre , Nervio Vago/inmunología , Estimulación del Nervio Vago/métodosRESUMEN
Resting state functional magnetic resonance imaging (rsfMRI) has shown the hierarchical organization of the human brain into large-scale complex networks, referred as resting state networks. This technique has turned into a promising translational research tool after the finding of similar resting state networks in non-human primates, rodents and other animal models of great value for neuroscience. Here, we demonstrate and characterize the presence of resting states networks in Microtus ochrogaster, the prairie vole, an extraordinary animal model to study complex human-like social behavior, with potential implications for the research of normal social development, addiction and neuropsychiatric disorders. Independent component analysis of rsfMRI data from isoflurane-anestethized prairie voles resulted in cortical and subcortical networks, including primary motor and sensory networks, but also included putative salience and default mode networks. We further discuss how future research could help to close the gap between the properties of the large scale functional organization and the underlying neurobiology of several aspects of social cognition. These results contribute to the evidence of preserved resting state brain networks across species and provide the foundations to explore the use of rsfMRI in the prairie vole for basic and translational research.
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Encéfalo/fisiología , Conectoma , Vías Aferentes , Animales , Arvicolinae , Encéfalo/diagnóstico por imagen , Vías Eferentes , Imagen por Resonancia Magnética , MasculinoRESUMEN
The habenula is an epithalamic structure differentiated into two nuclear complexes, medial (MHb) and lateral habenula (LHb). Recently, MHb together with its primary target, the interpeduncular nucleus (IP), have been identified as major players in mediating the aversive effects of nicotine. However, structures downstream of the MHb-IP axis, including the median (MnR) and caudal dorsal raphe nucleus (DRC), may contribute to the behavioral effects of nicotine. The afferent and efferent connections of the IP have hitherto not been systematically investigated with sensitive tracers. Thus, we placed injections of retrograde or anterograde tracers into different IP subdivisions or the MnR and additionally examined the transmitter phenotype of major IP and MnR afferents by combining retrograde tract tracing with immunofluorescence and in situ hybridization techniques. Besides receiving inputs from MHb and also LHb, we found that IP is reciprocally interconnected mainly with midline structures, including the MnR/DRC, nucleus incertus, supramammillary nucleus, septum, and laterodorsal tegmental nucleus. The bidirectional connections between IP and MnR proved to be primarily GABAergic. Regarding a possible topography of IP outputs, all IP subnuclei gave rise to descending projections, whereas major ascending projections, including focal projections to ventral hippocampus, ventrolateral septum, and LHb originated from the dorsocaudal IP. Our findings indicate that IP is closely associated to a distributed network of midline structures that modulate hippocampal theta activity and forms a node linking MHb and LHb with this network, and the hippocampus. Moreover, they support a cardinal role of GABAergic IP/MnR interconnections in the behavioral response to nicotine.
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Habénula/química , Núcleo Interpeduncular/química , Red Nerviosa/química , Núcleos del Rafe/química , Vías Aferentes/anatomía & histología , Vías Aferentes/química , Vías Aferentes/citología , Animales , Vías Eferentes/anatomía & histología , Vías Eferentes/química , Vías Eferentes/citología , Habénula/anatomía & histología , Habénula/citología , Núcleo Interpeduncular/anatomía & histología , Núcleo Interpeduncular/citología , Masculino , Red Nerviosa/anatomía & histología , Red Nerviosa/citología , Núcleos del Rafe/anatomía & histología , Núcleos del Rafe/citología , Ratas , Ratas WistarRESUMEN
Presympathetic neurons in the rostral ventrolateral medulla (RVLM) including the adrenergic cell groups play a major role in the modulation of several reflexes required for the control of sympathetic vasomotor tone and blood pressure (BP). Moreover, sympathetic vasomotor drive to the kidneys influence natriuresis and diuresis by inhibiting the cAMP/PKA pathway and redistributing the Na+/H+ exchanger isoform 3 (NHE3) to the body of the microvilli in the proximal tubules. In this study we aimed to evaluate the effects of renal afferents stimulation on (1) the neurochemical phenotype of Fos expressing neurons in the medulla oblongata and (2) the level of abundance and phosphorylation of NHE3 in the renal cortex. We found that electrical stimulation of renal afferents increased heart rate and BP transiently and caused activation of tyrosine hydroxylase (TH)-containing neurons in the RVLM and non-TH neurons in the NTS. Additionally, activation of the inhibitory renorenal reflex over a 30-min period resulted in increased natriuresis and diuresis associated with increased phosphorylation of NHE3 at serine 552, a surrogate for reduced activity of this exchanger, in the contralateral kidney. This effect was not dependent of BP changes considering that no effects on natriuresis or diuresis were found in the ipsilateral-stimulated kidney. Therefore, our data show that renal afferents leads to activation of catecholaminergic and non-catecholaminergic neurons in the medulla oblongata. When renorenal reflex is induced, NHE3 exchanger activity appears to be decreased, resulting in decreased sodium and water reabsorption in the contralateral kidney.
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Catecolaminas/metabolismo , Riñón/inervación , Riñón/metabolismo , Bulbo Raquídeo/metabolismo , Neuronas/metabolismo , Intercambiadores de Sodio-Hidrógeno/metabolismo , Vías Aferentes/citología , Vías Aferentes/metabolismo , Animales , Presión Sanguínea/fisiología , Estimulación Eléctrica , Frecuencia Cardíaca/fisiología , Inmunohistoquímica , Riñón/citología , Masculino , Bulbo Raquídeo/citología , Neuronas/citología , Fosforilación , Proteínas Proto-Oncogénicas c-fos/metabolismo , Ratas Wistar , Reflejo/fisiología , Intercambiador 3 de Sodio-Hidrógeno , Tirosina 3-Monooxigenasa/metabolismoRESUMEN
Low-intensity phototherapy using light fonts, like light-emitting diode (LED), in the red to infrared spectrum is a promising alternative for the treatment of pain. However, the underlying mechanisms by which LED phototherapy reduces acute pain are not yet well understood. This study investigated the analgesic effect of multisource LED phototherapy on the acute nocifensive behavior of mice induced by thermal and chemical noxious stimuli. The involvement of central afferent C fibers sensitive to capsaicin in this effect was also investigated. Mice exposed to multisource LED (output power 234, 390, or 780 mW and power density 10.4, 17.3, and 34.6 mW/cm2, respectively, from 10 to 30 min of stimulation with a wavelength of 890 nm) showed rapid and significant reductions in formalin- and acetic acid-induced nocifensive behavior. This effect gradually reduced but remained significant for up to 7 h after LED treatment in the last model used. Moreover, LED (390 mW, 17.3 mW/cm2/20 min) irradiation also reduced nocifensive behavior in mice due to chemical [endogenous (i.e., glutamate, prostaglandins, and bradykinin) or exogenous (i.e., formalin, acetic acid, TRPs and ASIC agonist, and protein kinase A and C activators)] and thermal (hot plate test) stimuli. Finally, ablating central afferent C fibers abolished LED analgesia. These experimental results indicate that LED phototherapy reduces the acute painful behavior of animals caused by chemical and thermal stimuli and that LED analgesia depends on the integrity of central afferent C fibers sensitive to capsaicin. These findings provide new information regarding the underlying mechanism by which LED phototherapy reduces acute pain. Thus, LED phototherapy may be an important tool for the management of acute pain.
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Vías Aferentes/fisiología , Conducta Animal/efectos de los fármacos , Capsaicina/farmacología , Calor , Luz , Fototerapia , Ácido Acético , Canales Iónicos Sensibles al Ácido/metabolismo , Adenilil Ciclasas/metabolismo , Vías Aferentes/efectos de los fármacos , Analgesia , Animales , Edema/patología , Femenino , Formaldehído , Ratones , Proteína Quinasa C/metabolismo , Reflejo , Canales de Potencial de Receptor Transitorio/metabolismoRESUMEN
INTRODUCTION: Our research group has described both morphological and electrophysiological changes in motor cortex pyramidal neurons associated with contralateral facial nerve injury in rats. However, little is known about those neural changes, which occur together with changes in surrounding glial cells. OBJECTIVE: To characterize the effect of the unilateral facial nerve injury on microglial proliferation and activation in the primary motor cortex. MATERIALS AND METHODS: We performed immunohistochemical experiments in order to detect microglial cells in brain tissue of rats with unilateral facial nerve lesion sacrificed at different times after the injury. We caused two types of lesions: reversible (by crushing, which allows functional recovery), and irreversible (by section, which produces permanent paralysis). We compared the brain tissues of control animals (without surgical intervention) and sham-operated animals with animals with lesions sacrificed at 1, 3, 7, 21 or 35 days after the injury. RESULTS: In primary motor cortex, the microglial cells of irreversibly injured animals showed proliferation and activation between three and seven days post-lesion. The proliferation of microglial cells in reversibly injured animals was significant only three days after the lesion. CONCLUSIONS: Facial nerve injury causes changes in microglial cells in the primary motor cortex. These modifications could be involved in the generation of morphological and electrophysiological changes previously described in the pyramidal neurons of primary motor cortex that command facial movements.
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Traumatismos del Nervio Facial/patología , Parálisis Facial/fisiopatología , Microglía/patología , Corteza Motora/patología , Vías Aferentes , Animales , Axotomía , División Celular , Músculos Faciales/inervación , Traumatismos del Nervio Facial/complicaciones , Traumatismos del Nervio Facial/fisiopatología , Parálisis Facial/etiología , Parálisis Facial/patología , Masculino , Compresión Nerviosa , Regeneración Nerviosa , Células Piramidales/patología , Células Piramidales/fisiología , Distribución Aleatoria , Ratas , Ratas Wistar , Factores de TiempoRESUMEN
Resumen Introducción. El grupo de investigación del Laboratorio de Neurofisiología Comportamental de la Universidad Nacional de Colombia ha descrito modificaciones estructurales y electrofisiológicas en neuronas piramidales de la corteza motora producidas por la lesión del nervio facial contralateral en ratas. Sin embargo, poco se sabe sobre la posibilidad de que dichos cambios neuronales se acompañen también de modificaciones en las células gliales circundantes. Objetivo. Caracterizar el efecto de la lesión unilateral del nervio facial sobre la activación y proliferación de las células de la microglía en la corteza motora primaria contralateral en ratas. Materiales y métodos. Se hicieron pruebas de inmunohistoquímica para detectar las células de la microglía en el tejido cerebral de ratas sometidas a lesión del nervio facial, las cuales se sacrificaron en distintos momentos después de la intervención. Se infligieron dos tipos de lesiones: reversible (por compresión, lo cual permite la recuperación de la función) e irreversible (por corte, lo cual provoca parálisis permanente). Los tejidos cerebrales de los animales sin lesión (grupo de control absoluto) y de aquellos sometidos a falsa cirugía se compararon con los de los animales lesionados sacrificados 1, 2, 7, 21 y 35 días después de la lesión. Resultados. Las células de la microglía en la corteza motora de los animales lesionados irreversiblemente mostraron signos de proliferación y activación entre el tercero y séptimo días después de la lesión. La proliferación de las células de la microglía en animales con lesión reversible fue significativa solo a los tres días de infligida la lesión. Conclusiones. La lesión del nervio facial produce modificaciones en las células de la microglía de la corteza motora primaria. Estas modificaciones podrían estar involucradas en los cambios morfológicos y electrofisiológicos descritos en las neuronas piramidales de la corteza motora que comandan los movimientos faciales.
Abstract Introduction: Our research group has described both morphological and electrophysiological changes in motor cortex pyramidal neurons associated with contralateral facial nerve injury in rats. However, little is known about those neural changes, which occur together with changes in surrounding glial cells. Objective: To characterize the effect of the unilateral facial nerve injury on microglial proliferation and activation in the primary motor cortex. Materials and methods: We performed immunohistochemical experiments in order to detect microglial cells in brain tissue of rats with unilateral facial nerve lesion sacrificed at different times after the injury. We caused two types of lesions: reversible (by crushing, which allows functional recovery), and irreversible (by section, which produces permanent paralysis). We compared the brain tissues of control animals (without surgical intervention) and sham-operated animals with animals with lesions sacrificed at 1, 3, 7, 21 or 35 days after the injury. Results: In primary motor cortex, the microglial cells of irreversibly injured animals showed proliferation and activation between three and seven days post-lesion. The proliferation of microglial cells in reversibly injured animals was significant only three days after the lesion. Conclusions: Facial nerve injury causes changes in microglial cells in the primary motor cortex. These modifications could be involved in the generation of morphological and electrophysiological changes previously described in the pyramidal neurons of primary motor cortex that command facial movements.
Asunto(s)
Animales , Masculino , Ratas , Microglía/patología , Traumatismos del Nervio Facial/patología , Parálisis Facial/fisiopatología , Corteza Motora/patología , Factores de Tiempo , Distribución Aleatoria , Vías Aferentes , División Celular , Ratas Wistar , Células Piramidales/fisiología , Células Piramidales/patología , Axotomía , Traumatismos del Nervio Facial/complicaciones , Traumatismos del Nervio Facial/fisiopatología , Músculos Faciales/inervación , Parálisis Facial/etiología , Parálisis Facial/patología , Compresión Nerviosa , Regeneración NerviosaRESUMEN
Most of the endogenous pain modulation (EPM) involves the spinal dorsal horn (SDH). EPM including diffuse noxious inhibitory controls have been extensively described in oligoneuronal electrophysiological recordings but less attention had been paid to responses of the SDH neuronal population to heterotopic noxious stimulation (HNS). Spinal somatosensory-evoked potentials (SEP) offer the possibility to evaluate the neuronal network behavior, reflecting the incoming afferent volleys along the entry root, SDH interneuron activities and the primary afferent depolarization. SEP from de lumbar cord dorsum were evaluated during mechanical heterotopic noxious stimuli. Sprague-Dawley rats (n = 12) were Laminectomized (T10-L3). The sural nerve of the left hind paw was electrically stimulated (5 mA, 0.5 ms, 0.05 Hz) to induce lumbar SEP. The HNS (mechanic clamp) was applied sequentially to the tail, right hind paw, right forepaw, muzzle and left forepaw during sural stimulation. N wave amplitude decreases (-16.6 %) compared to control conditions when HNS was applied to all areas of stimulation. This effect was more intense for muzzle stimulation (-23.5 %). N wave duration also decreased by -23.6 %. HNS did not change neither the amplitude nor the duration of the P wave but dramatically increases the dispersion of these two parameters. The results of the present study strongly suggest that a HNS applied to different parts of the body is able to reduce the integrated electrical response of the SDH, suggesting that not only wide dynamic range neurons but many others in the SDH are modulated by the EPM.
Asunto(s)
Vías Aferentes/fisiología , Potenciales Evocados Somatosensoriales/fisiología , Inhibición Neural/fisiología , Dolor/fisiopatología , Células del Asta Posterior/fisiología , Animales , Estimulación Eléctrica , Lateralidad Funcional , Laminectomía , Ratones , Dolor/etiología , Estimulación Física/efectos adversos , Ratas , Ratas Sprague-Dawley , Estadísticas no Paramétricas , Nervio Sural/fisiologíaRESUMEN
Despite the abundance of evidence that supports the important role of aortic and carotid afferents to short-term regulation of blood pressure and detection of variation in the arterial PO2 , PCO2 and pH, relatively little is known regarding the role of these afferents during changes in the volume and composition of extracellular compartments. The present study sought to determine the involvement of these afferents in the renal vasodilation and sympathoinhibition induced by hypertonic saline (HS) infusion. Sinoaortic-denervated and sham male Wistar rats were anaesthetised with intravenous (i.v.) urethane (1.2 g/kg body weight (bw)) prior to the measurement of the mean arterial pressure (MAP), renal vascular conductance (RVC) and renal sympathetic nerve activity (RSNA). In the sham group, the HS infusion (3 mol/L NaCl, 1.8 mL/kg bw, i.v.) induced transient hypertension (12 ± 4 mmHg from baseline, peak at 10 min; P < 0.05), an increase in RVC (127 ± 9% and 150 ± 13% from baseline, at 20 and 60 min respectively; P < 0.05) and a decrease in RSNA (-34 ± 10% and -29 ± 5% from baseline, at 10 and 60 min respectively; P < 0.05). In sinoaortic-denervated rats, HS infusion promoted a sustained pressor response (30 ± 5 and 17 ± 6 mmHg of baseline values, at 10 and 30 min respectively; P < 0.05) and abolished the increase in RVC (85 ± 8% from baseline, at 10 min) and decrease in RSNA (-4 ± 3% from baseline, at 10 min). These results suggest that aortic and carotid afferents are involved in cardiovascular and renal sympathoinhibition responses induced by acute hypernatremia.
Asunto(s)
Aorta/inervación , Seno Carotídeo/inervación , Hipernatremia/fisiopatología , Riñón/inervación , Inhibición Neural , Sistema Nervioso Simpático/fisiopatología , Vasodilatación , Vías Aferentes/fisiopatología , Animales , Presión Arterial , Barorreflejo , Modelos Animales de Enfermedad , Hipernatremia/sangre , Masculino , Ratas Wistar , Sodio/sangre , Simpatectomía , Sistema Nervioso Simpático/cirugía , Factores de TiempoRESUMEN
BACKGROUND: The antiepileptic drugs carbamazepine and gabapentin are effective in treating neuropathic pain and trigeminal neuralgia. In the present study, to analyze the effects of carbamazepine and gabapentin on neuronal excitation in the spinal trigeminal subnucleus caudalis (Sp5c) in the medulla oblongata, we recorded temporal changes in nociceptive afferent activity in the Sp5c of trigeminal nerve-attached brainstem slices of neonatal rats using a voltage-sensitive dye imaging technique. RESULTS: Electrical stimulation of the trigeminal nerve rootlet evoked changes in the fluorescence intensity of dye in the Sp5c. The optical signals were composed of two phases, a fast component with a sharp peak followed by a long-lasting component with a period of more than 500 ms. This evoked excitation was not influenced by administration of carbamazepine (10, 100 and 1,000 µM) or gabapentin (1 and 10 µM), but was increased by administration of 100 µM gabapentin. This evoked excitation was increased further in low Mg(2+) (0.8 mM) conditions, and this effect of low Mg(2+) concentration was antagonized by 30 µM DL-2-amino-5-phosphonopentanoic acid (AP5), a N-methyl-D-aspartate (NMDA) receptor blocker. The increased excitation in low Mg(2+) conditions was also antagonized by carbamazepine (1,000 µM) and gabapentin (100 µM). CONCLUSION: Carbamazepine and gabapentin did not decrease electrically evoked excitation in the Sp5c in control conditions. Further excitation in low Mg(2+) conditions was antagonized by the NMDA receptor blocker AP5. Carbamazepine and gabapentin had similar effects to AP5 on evoked excitation in the Sp5c in low Mg(2+) conditions. Thus, we concluded that carbamazepine and gabapentin may act by blocking NMDA receptors in the Sp5c, which contributes to its anti-hypersensitivity in neuropathic pain.