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Astrocytes are determinants for the functioning of the CNS. They respond to neuronal activity with calcium increases and can in turn modulate synaptic transmission, brain plasticity as well as cognitive processes. Astrocytes display sensory-evoked calcium responses in different brain structures related to the discriminative system of most sensory modalities. In particular, noxious stimulation evoked calcium responses in astrocytes in the spinal cord, the hippocampus, and the somatosensory cortex. However, it is not clear if astrocytes are involved in pain. Pain is a private, personal, and complex experience that warns us about potential tissue damage. It is a perception that is not linearly associated with the amount of tissue damage or nociception; instead, it is constructed with sensory, cognitive, and affective components and depends on our previous experiences. However, it is not fully understood how pain is created from nociception. In this perspective article, we provide an overview of the mechanisms and neuronal networks that underlie the perception of pain. Then we proposed that coherent activity of astrocytes in the spinal cord and pain-related brain areas could be important in binding sensory, affective, and cognitive information on a slower time scale.
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Glutamatergic transmission through NMDA receptors (NMDARs) is important for the function of peripheral tissues. In the bone, NMDARs and its co-agonist, D-serine participate in all the phases of the remodeling. In the vasculature, NMDARs exerts a tonic vasodilation decreasing blood perfusion in the corpus cavernosum and the filtration rate in the renal glomerulus. NMDARs are relevant for the skin turnover regulating the proliferation and differentiation of keratinocytes and the formation of the cornified envelope (CE). The interference with NMDAR function in the skin leads to a slow turnover and repair. As occurs with the brain and cognitive functions, the manifestations of a hypofunction of NMDARs resembles those observed during aging. This raises the question if the deterioration of the glomerular vasculature, the bone remodeling and the skin turnover associated with age could be related with a hypofunction of NMDARs. Furthermore, the interference of D-serine and the effects of its supplementation on these tissues, suggest that a decrease of D-serine could account for this hypofunction pointing out D-serine as a potential therapeutic target to reduce or even prevent the detriment of the peripheral tissue associated with aging.
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Resumen El trastorno por atracón (TA) es una condición compleja en la que se han descrito diferentes aspectos clínicos y fallas neuropsicológicas en los sujetos que lo padecen. En este estudio se compararon variables clínicas (VC), neuropsicológicas (VNPS) y psicofisiológicas (VPFS) entre participantes sanos (n = 15) y con TA (n = 15) evaluados en la [Omitido por el editor]. Las VC incluyeron el inventario del anhelo por el consumo de alimentos (IACA), sintomatología depresiva (SD), ansiedad (SA) e impulsividad. Se utilizaron la Tarea de Cartas de Wisconsin para evaluar flexibilidad cognitiva (FC) y la Tarea de Señal de Alto para control inhibitorio (CI) dentro de las VNPS; en las VPFS se obtuvo la variabilidad de la frecuencia cardiaca (VFC) durante una prueba de exposición a imágenes de alimentos. Los resultados muestran que los participantes con TA obtuvieron puntuaciones mayores en los instrumentos IACA (p < .0001), SD (p < .0001) y SA (p < .0001); mientras que en las VNPS mostraron fallas en la FC con incremento en el porcentaje de errores totales (p = .01), errores perseverativos (p = .03) y CI (p = .004). Para las VPFS se encontró una reducción de la VFC (p < .0001) en aquellos participantes con TA.
Abstract Binge eating disorder (BED) is a complex condition in which different clinical aspects and neuropsychological faults have been treated in subjects who have it. In this study, clinical (VC), neuropsychological (VNPS) and psychophysiological (VPFS) variables were compared between healthy participants (n = 15) and with BED (n = 15) evaluated in the medicine school of the Autonomous University of Querétaro. The VC included the evaluation of the food craving scale (FCS), depressive symptomatology (DS), anxiety (AS) and impulsivity. It is used in the Wisconsin Cards Sorting Test for Cognitive Flexibility (CF) and the Stop Signal Task for Inhibitory Control (IC) within the VNPS; In the VPFS, the heart rate variability (HRV) was obtained during an exposure test to food images. The results showed that the participants obtained high scores in the evaluation instruments for FCS (p < .0001), SD (p < .0001) and SA (p < .0001); whereas in the VNPS it failed in the FC with an increase in the percentage of total errors (p = .01), perseverative errors (p = .03) and CI (p = .004). For the VPFS, a reduction in HRV (p < .0001) was found in those participants with AT.
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BACKGROUND: Understanding the configuration of neural circuits and the specific role of distinct cortical neuron types involved in behavior, requires the study of structure-function and connectivity relationships with single cell resolution in awake behaving animals. Despite head-fixed behaving rats have been used for in vivo measuring of neuronal activity, it is a concern that head fixation could change the performance of behavioral task. NEW METHOD: We describe the procedures for efficiently training Wistar rats to develop a behavioral task, involving planning and execution of a qualified movement in response to a visual cue under head-fixed conditions. The behavioral and movement performance in freely moving vs head-fixed conditions was analyzed. RESULTS: The best behavioral performance was obtained in the rats that were trained first in freely moving conditions and then placed in a head-restrained condition compared with the animals which first were habituated to head-restriction and then learned the task. Moreover, head restriction did not alter the movement performance. Stable juxtacellular recordings from sensorimotor cortex neurons were obtained while the rats were performing forelimb movements. Biocytin electroporation and retrograde tracer injections, permits identify the hodology of individual long-range projecting neurons. COMPARISON WITH EXISTING METHODS: Our method shows no difference in the behavioral performance of head fixed and freely moving conditions. Also includes a computer aided design of a discrete and ergonomic head-post allowing enough stability to perform juxtacellular recording and labeling of cortical neurons. CONCLUSIONS: Our method is suitable for the in vivo characterization of neuronal circuits and their long-range connectivity.
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Comportamento Animal/fisiologia , Condicionamento Operante/fisiologia , Conectoma/métodos , Eletrocorticografia/métodos , Atividade Motora/fisiologia , Neurônios/fisiologia , Restrição Física , Córtex Sensório-Motor/fisiologia , Animais , Eletroporação , Membro Anterior/fisiologia , Movimentos da Cabeça/fisiologia , Técnicas de Rastreamento Neuroanatômico , Desempenho Psicomotor/fisiologia , Ratos , Ratos WistarRESUMO
BACKGROUND: Movement performance depends on the synaptic interactions generated by coherent parallel sensorimotor cortical outputs to different downstream targets. The major outputs of the neocortex to subcortical structures are driven by pyramidal tract neurons (PTNs) located in layer 5B. One of the main targets of PTNs is the spinal cord through the corticospinal (CS) system, which is formed by a complex collection of distinct CS circuits. However, little is known about intracortical synaptic interactions that originate CS commands and how different populations of CS neurons are functionally organized. To further understand the functional organization of the CS system, we analyzed the activity of unambiguously identified CS neurons projecting to different zones of the same spinal cord segment using two-photon calcium imaging and retrograde neuronal tracers. RESULTS: Sensorimotor cortex slices obtained from transgenic mice expressing GCaMP6 funder the Thy1 promoter were used to analyze the spontaneous calcium transients in layer 5 pyramidal neurons. Distinct subgroups of CS neurons projecting to dorsal horn and ventral areas of the same segment show more synchronous activity between them than with other subgroups. CONCLUSIONS: The results indicate that CS neurons projecting to different spinal cord zones segregated into functional ensembles depending on their hodology, suggesting that a modular organization of CS outputs controls sensorimotor behaviors in a coordinated manner.
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Conectoma , Tratos Piramidais/fisiologia , Medula Espinal/fisiologia , Animais , Cálcio/metabolismo , Imunofluorescência/métodos , Camundongos , Camundongos Transgênicos , Córtex Motor/metabolismo , Córtex Motor/fisiologia , Vias Neurais/metabolismo , Vias Neurais/fisiologia , Técnicas de Rastreamento Neuroanatômico/métodos , Neurônios/fisiologia , Tratos Piramidais/metabolismo , Medula Espinal/metabolismoRESUMO
Recent results implicate a new original mechanism involving oxytocin (OT), as a mediator via descending fibers of the paraventricular hypothalamic nucleus (PVN), in antinociception and analgesia. In rats electrical stimulation of the PVN or topical application of OT selectively inhibits A-delta and C fiber responses in superficial dorsal horn neurons, and this inhibition is reversed by a selective OT antagonist. However, little is known about the mechanisms and the spinal elements participating in this phenomenon. Here we show that topical application of bicuculline blocks the effects produced by PVN electrical stimulation or OT application. PVN electrical stimulation also activates a subpopulation of neurons in lamina II. These PVN-On cells are responsible for the amplification of local GABAergic inhibition. This result reinforces the suggestion that a supraspinal descending control of pain processing uses a specific neuronal pathway in the spinal cord in order to produce antinociception involving a GABAergic interneuron. Moreover, the topical administration of naloxone or a mu-opiate receptor antagonist beta-funaltrexamine only partially blocks the inhibitory effects produced by OT application or PVN electrical stimulation. Thus, this OT mechanism only involves opiate participation to a minor extent. The OT-specific, endogenous descending pathway represents an interesting mechanism to resolve chronic pain problems in special the neuropathic pain.
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Hipotálamo/metabolismo , Neurônios/metabolismo , Nociceptores/metabolismo , Ocitocina/metabolismo , Medula Espinal/metabolismo , Raízes Nervosas Espinhais/metabolismo , Animais , Bicuculina/farmacologia , Vias Eferentes/citologia , Vias Eferentes/metabolismo , Estimulação Elétrica , Antagonistas GABAérgicos/farmacologia , Hipotálamo/citologia , Antagonistas de Entorpecentes/farmacologia , Fibras Nervosas Mielinizadas/efeitos dos fármacos , Fibras Nervosas Mielinizadas/metabolismo , Fibras Nervosas Mielinizadas/ultraestrutura , Fibras Nervosas Amielínicas/efeitos dos fármacos , Fibras Nervosas Amielínicas/metabolismo , Fibras Nervosas Amielínicas/ultraestrutura , Inibição Neural/efeitos dos fármacos , Inibição Neural/fisiologia , Neurônios/citologia , Nociceptores/citologia , Nociceptores/efeitos dos fármacos , Peptídeos Opioides/metabolismo , Ocitocina/farmacologia , Dor/metabolismo , Dor/fisiopatologia , Células do Corno Posterior/citologia , Células do Corno Posterior/efeitos dos fármacos , Células do Corno Posterior/metabolismo , Ratos , Ratos Wistar , Medula Espinal/citologia , Medula Espinal/efeitos dos fármacos , Raízes Nervosas Espinhais/citologia , Raízes Nervosas Espinhais/efeitos dos fármacos , Transmissão Sináptica/efeitos dos fármacos , Transmissão Sináptica/fisiologia , Ácido gama-Aminobutírico/metabolismoRESUMO
In anaesthetized rats, we tested whether the unit activity of dorsal horn neurons that receive nociceptive input is modulated by electrical stimulation of the hypothalamic paraventricular nucleus (PVN). An electrophysiological mapping of dorsal horn neurons at L3-L4 let us choose cells responding to a receptive field located in the toes region of the left hindpaw. Dorsal horn neurons were classified according to their response properties to peripheral stimulation. Wide Dynamic Range (WDR) cells responding to electrical stimulation of the peripheral receptive field and presenting synaptic input of Adelta, Abeta, and C-fibers were studied. Suspected interneurons that are typically silent and lack peripheral receptive field responses were also analyzed. PVN electrical stimulation inhibits Adelta (-55.0+/-10.2%), C-fiber (-73.1+/-6.7%), and post-discharge (-75.0+/-8.9%) peripheral activation in WDR cells, and silent interneurons were activated. So, this last type of interneuron was called a PVN-ON cell. In WDR cells, the inhibition of peripheral responses caused by PVN stimulation was blocked by intrathecal administration of a specific oxytocin antagonist or bicuculline. However, PVN-ON cell activation was blocked by the same specific oxytocin antagonist, but not by bicuculline. Our results suggest that PVN stimulation inhibits nociceptive peripheral-evoked responses in WDR neurons by a descending oxytocinergic pathway mediated by GABAergic PVN-ON cells. We discuss our observation that the PVN electrical stimulation selectively inhibits Adelta and C-fiber activity without affecting Abeta fibers. We conclude that Adelta and C-fibers receive a presynaptic inhibition mediated by GABA.
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Inibição Neural/fisiologia , Ocitocina/metabolismo , Núcleo Hipotalâmico Paraventricular/fisiologia , Células do Corno Posterior/fisiologia , Ácido gama-Aminobutírico/metabolismo , Potenciais de Ação/efeitos dos fármacos , Potenciais de Ação/fisiologia , Animais , Bicuculina/farmacologia , Mapeamento Encefálico , Estimulação Elétrica/métodos , Antagonistas GABAérgicos/farmacologia , Fibras Nervosas/fisiologia , Fibras Nervosas/efeitos da radiação , Inibição Neural/efeitos dos fármacos , Ocitocina/análogos & derivados , Ocitocina/antagonistas & inibidores , Ocitocina/farmacologia , Núcleo Hipotalâmico Paraventricular/efeitos da radiação , Células do Corno Posterior/efeitos dos fármacos , Ratos , Ratos WistarRESUMO
In recent years, oxytocin has been implicated in a wide diversity of functions. The role of oxytocin in analgesia and pain modulation represents an important new function of an endogenous system controlling sensorial information. The paraventricular (PV) nucleus of the hypothalamus is one of the most important sources of oxytocin, and it has a very well-defined projection to the spinal cord. The location of this PV spinal cord projection correlates well with oxytocin binding sites at the dorsal horn of the spinal cord. In this work, we used rats with a chronic (46 days) sciatic loose ligature, an electrical stimulating electrode, and an intrathecal cannula, which reached the L4-L5 levels of the spinal cord. We compared the oxytocin effects with electrical stimulation of the PV and observed a significant reduction of the withdrawal responses to mechanical and cold stimulation applied to the ipsilateral and contralateral hind paws. An oxytocin antagonist administered intrathecally blocked the PV effects. Naloxone was also intrathecally injected 2 min before the PV stimulation, and we also observed a significant reduction of the withdrawal responses; however, this reduction was less pronounced. Our results support the hypothesis that oxytocin is part of the descending inhibitory control mechanisms having an important antinociceptive action. We cannot exclude a minor opiate participation in the OT action.