RESUMEN
Survival requires the selection of appropriate behaviour in response to threats, and dysregulated defensive reactions are associated with psychiatric illnesses such as post-traumatic stress and panic disorder1. Threat-induced behaviours, including freezing and flight, are controlled by neuronal circuits in the central amygdala (CeA)2; however, the source of neuronal excitation of the CeA that contributes to high-intensity defensive responses is unknown. Here we used a combination of neuroanatomical mapping, in vivo calcium imaging, functional manipulations and electrophysiology to characterize a previously unknown projection from the dorsal peduncular (DP) prefrontal cortex to the CeA. DP-to-CeA neurons are glutamatergic and specifically target the medial CeA, the main amygdalar output nucleus mediating conditioned responses to threat. Using a behavioural paradigm that elicits both conditioned freezing and flight, we found that CeA-projecting DP neurons are activated by high-intensity threats in a context-dependent manner. Functional manipulations revealed that the DP-to-CeA pathway is necessary and sufficient for both avoidance behaviour and flight. Furthermore, we found that DP neurons synapse onto neurons within the medial CeA that project to midbrain flight centres. These results elucidate a non-canonical top-down pathway regulating defensive responses.
Asunto(s)
Reacción de Prevención , Núcleo Amigdalino Central , Vías Nerviosas , Neuronas , Reacción de Prevención/fisiología , Núcleo Amigdalino Central/citología , Núcleo Amigdalino Central/fisiología , Neuronas/fisiología , Corteza Prefrontal/citología , Corteza Prefrontal/fisiología , Fármacos actuantes sobre Aminoácidos Excitadores/farmacología , Ácido Glutámico/metabolismo , Vías Nerviosas/fisiología , Calcio/análisis , Electrofisiología , Puente/citología , Puente/fisiologíaRESUMEN
Neuropeptide S (NPS) was postulated to be a wake-promoting neuropeptide with unknown mechanism, and a mutation in its receptor (NPSR1) causes the short sleep duration trait in humans. We investigated the role of different NPS+ nuclei in sleep/wake regulation. Loss-of-function and chemogenetic studies revealed that NPS+ neurons in the parabrachial nucleus (PB) are wake-promoting, whereas peri-locus coeruleus (peri-LC) NPS+ neurons are not important for sleep/wake modulation. Further, we found that a NPS+ nucleus in the central gray of the pons (CGPn) strongly promotes sleep. Fiber photometry recordings showed that NPS+ neurons are wake-active in the CGPn and wake/REM-sleep active in the PB and peri-LC. Blocking NPS-NPSR1 signaling or knockdown of Nps supported the function of the NPS-NPSR1 pathway in sleep/wake regulation. Together, these results reveal that NPS and NPS+ neurons play dichotomous roles in sleep/wake regulation at both the molecular and circuit levels.
Asunto(s)
Neuropéptidos , Sueño , Humanos , Sueño/fisiología , Puente/fisiología , Locus Coeruleus/fisiología , Neuronas/metabolismo , Neuropéptidos/metabolismo , Receptores Acoplados a Proteínas G/metabolismoRESUMEN
Shape and size of the nasopharyngeal airway is controlled by muscles innervated facial, glossopharyngeal, vagal, and hypoglossal cranial nerves. Contrary to brainstem networks that drive facial, vagal and hypoglossal nerve activities (FNA, VNA, HNA) the discharge patterns and origins of glossopharyngeal nerve activity (GPNA) remain poorly investigated. Here, an in situ perfused brainstem preparation (n=19) was used for recordings of GPNA in relation to phrenic (PNA), FNA, VNA and HNA. Brainstem transections were performed (n=10/19) to explore the role of pontomedullary synaptic interactions in generating GPNA. GPNA generally mirrors FNA and HNA discharge patterns and displays pre-inspiratory activity relative to the PNA, followed by robust inspiratory discharge in coincidence with PNA. Postinspiratory (early expiratory) discharge was, contrary to VNA, generally absent in FNA, GPNA or HNA. As described previously FNA and HNA discharge was virtually eliminated after pontomedullary transection while an apneustic inspiratory motor discharge was maintained in PNA, VNA and GPNA. After brainstem transection GPNA displayed an increased tonic activity starting during mid-expiration and thus developed prolonged pre-inspiratory activity compared to control. In conclusion respiratory GPNA reflects FNA and HNA which implies similar function in controlling upper airway patency during breathing. That GPNA preserved its pre-inspiratory/inspiratory discharge pattern in relation PNA after pontomedullary transection suggest that GPNA premotor circuits may have a different anatomical distribution compared HNA and FNA and thus may therefore hold a unique role in preserving airway patency.
Asunto(s)
Nervio Glosofaríngeo , Animales , Nervio Glosofaríngeo/fisiología , Bulbo Raquídeo/fisiología , Puente/fisiología , Nervio Frénico/fisiología , Respiración , Nervio Hipogloso/fisiología , Masculino , Potenciales de Acción/fisiologíaRESUMEN
ABSTRACT Transaxonal degenerations result from neuronal death or the interruption of synaptic connections among neuronal structures. These degenerations are not common but may be recognized by conventional magnetic resonance imaging. Objective: The learning objectives of this review include recognition of the imaging characteristics of transaxonal degenerations involving cerebellar connections, the identification of potential encephalic lesions that can lead to these degenerations and correlation of the clinical manifestations with imaging findings that reflect this involvement. Methods: In this report, we review the neuroanatomical knowledge that provides a basis for identifying potential lesions that can result in these degenerations involving cerebellar structures. Results: Hypertrophic olivary degeneration results from an injury that interrupts any of the components of the Guillain-Mollaret triangle. In this work, we describe cases of lesions in the dentate nucleus and central tegmental tract. The crossed cerebellar diaschisis presents specific imaging findings and clinical correlations associated with its acute and chronic phases. The Wallerian degeneration of the middle cerebellar peduncle is illustrated by fiber injury of the pontine cerebellar tracts. A T2-hyperintensity in the dentate nucleus due to a thalamic acute lesion (in ventral lateral nuclei) is also described. Each condition described here is documented by MRI images and is accompanied by teaching points and an anatomical review of the pathways involved. Conclusion: Neurologists and radiologists need to become familiar with the diagnosis of these conditions since their presentations are peculiar and often subtle, and can easily be misdiagnosed as ischemic events, degenerative disease, demyelinating disease or even tumors.
RESUMO Degenerações transaxonais resultam da morte neuronal ou da interrupção de conexões sinápticas entre estruturas neurais. Essas degenerações não são comuns, mas podem ser reconhecidas por imagens de ressonância magnética convencional. Objetivo: Os objetivos de aprendizado desta revisão incluem o reconhecimento das características de imagem de degenerações transaxonais envolvendo conexões cerebelares, a identificação de possíveis lesões encefálicas que podem levar a essas degenerações e a correlação das manifestações clínicas com os achados de imagem que refletem esse envolvimento. Métodos: Neste artigo, revisamos conhecimentos neuroanatômicos que fornecem a base para identificar possíveis lesões que podem resultar nessas degenerações envolvendo estruturas cerebelares. Resultados: A degeneração olivar hipertrófica resulta de uma lesão que interrompe algum dos componentes do triângulo de Guillain-Mollaret. Neste trabalho, descrevemos casos de lesões no núcleo denteado e no trato tegmentar central. A diásquise cerebelar cruzada apresenta achados de imagem específicos e correlações clínicas associadas às suas fases aguda e crônica. A degeneração walleriana dos pedúnculos cerebelares médios é ilustrada pela lesão dos tratos pontino-cerebelares. Uma hiperintensidade em T2 do núcleo denteado devido a uma lesão talâmica aguda (no núcleo ventrolateral) também é descrita. Cada condição aqui descrita é documentada por imagens de ressonância magnética e é acompanhada por pontos didáticos e uma revisão anatômica das vias envolvidas. Conclusão: Neurologistas e radiologistas precisam estar familiarizados com o diagnóstico dessas condições, uma vez que suas apresentações são peculiares e frequentemente sutis, e podem ser facilmente equivocadamente diagnosticadas como lesões isquêmicas, doenças degenerativas, desmielinizantes, ou mesmo tumorais.
Asunto(s)
Núcleo Olivar , Cerebelo , Encéfalo , Puente/fisiología , Imagen por Resonancia MagnéticaRESUMEN
The arterial partial pressure (P CO2) of carbon dioxide is virtually constant because of the close match between the metabolic production of this gas and its excretion via breathing. Blood gas homeostasis does not rely solely on changes in lung ventilation, but also to a considerable extent on circulatory adjustments that regulate the transport of CO2 from its sites of production to the lungs. The neural mechanisms that coordinate circulatory and ventilatory changes to achieve blood gas homeostasis are the subject of this review. Emphasis will be placed on the control of sympathetic outflow by central chemoreceptors. High levels of CO2 exert an excitatory effect on sympathetic outflow that is mediated by specialized chemoreceptors such as the neurons located in the retrotrapezoid region. In addition, high CO2 causes an aversive awareness in conscious animals, activating wake-promoting pathways such as the noradrenergic neurons. These neuronal groups, which may also be directly activated by brain acidification, have projections that contribute to the CO2-induced rise in breathing and sympathetic outflow. However, since the level of activity of the retrotrapezoid nucleus is regulated by converging inputs from wake-promoting systems, behavior-specific inputs from higher centers and by chemical drive, the main focus of the present manuscript is to review the contribution of central chemoreceptors to the control of autonomic and respiratory mechanisms.
Asunto(s)
Humanos , Neuronas Adrenérgicas/fisiología , Fenómenos Fisiológicos Cardiovasculares , Células Quimiorreceptoras/fisiología , Fenómenos Fisiológicos Respiratorios , Tronco Encefálico/fisiología , Monóxido de Carbono/metabolismo , Sistema Nervioso Central/fisiología , Bulbo Raquídeo/fisiología , Puente/fisiología , Sistema Nervioso Simpático/fisiologíaRESUMEN
The pedunculopontine nucleus (PPN) is located in the dorso-lateral part of the ponto-mesencephalic tegmentum. The PPN is composed of two groups of neurons: one containing acetylcholine, and the other containing non-cholinergic neurotransmitters (GABA, glutamate). The PPN is connected reciprocally with the limbic system, the basal ganglia nuclei (globus pallidus, substantia nigra, subthalamic nucleus), and the brainstem reticular formation. The caudally directed corticolimbic-ventral striatal-ventral pallidal-PPN-pontomedullary reticular nuclei-spinal cord pathway seems to be involved in the initiation, acceleration, deceleration, and termination of locomotion. This pathway is under the control of the deep cerebellar and basal ganglia nuclei at the level of the PPN, particularly via potent inputs from the medial globus pallidus, substantia nigra pars reticulata and subthalamic nucleus. The PPN sends profuse ascending cholinergic efferent fibers to almost all the thalamic nuclei, to mediate phasic events in rapid-eye-movement sleep. Experimental evidence suggests that the PPN, along with other brain stem nuclei, is also involved in anti-nociception and startle reactions. In idiopathic Parkinson's disease (IPD) and parkinson plus syndrome, overactive pallidal and nigral inhibitory inputs to the PPN may cause sequential occurrences of PPN hypofunction, decreased excitatory PPN input to the substantia nigra, and aggravation of striatal dopamine deficiency. In addition, neuronal loss in the PPN itself may cause dopamine-r esistant parkinsonian deficits, including gait disorders, postural instability and sleep disturbances. In patients with IPD, such deficits may improve after posteroventral pallidotomy, but not after thalamotomy. One of the possible explanations for such differences is that dopamine-resistant parkinsonian deficits are mediated to the PPN by the descending pallido-PPN inhibitory fibers, which leave the pallido-thalamic pathways before they reach the thalamic targets.
Asunto(s)
Humanos , Animales , Ganglios Basales/citología , Mesencéfalo/fisiología , Mesencéfalo/citología , Trastornos del Movimiento/etiología , Puente/fisiología , Puente/citología , Tálamo/citologíaRESUMEN
Introducción. El condicionamiento aversivo gustativo esuna forma de aprendizaje asociativo en el que ciertas cualidadesde un alimento (principalmente su sabor) se asocian con determinadasconsecuencias viscerales negativas derivadas de su ingestión.El establecimiento de este aprendizaje depende de procesos de integración gustativo-visceral llevados a cabo en el sistema nerviosocentral. Desarrollo. En el presente manuscrito se pretendeofrecer una visión global de los centros y conexiones más relevantespara la formación del aprendizaje aversivo gustativo (AAG).Conclusiones. Numerosos investigadores consideran que el nivelinicial de integración se sitúa en el núcleo parabraquial. A priori,podría considerarse que el AAG, dado su carácter básico y vital, seforma y completa a este nivel troncoencefálico, sin necesitar la intervenciónde estructuras superiores de procesamiento. No obstante,en la bibliografía sobre el AAG existe un amplio conjunto dedatos, tanto neuroanatómicos como neuroconductuales, mediantelos cuales parece evidenciarse que la formación del AAG requierecomplejas interacciones entre el núcleo parabraquial y determinadasestructuras prosencefálicas, como la corteza insular o la amígdala,entre otras
Introduction. Taste aversion conditioning is a form of associative learning in which certain qualities of a food(mainly its taste) are associated to specific negative visceral consequences that derive from eating it. Establishing thislearning depends on gustatory-visceral integration processes carried out in the central nervous system. Development. In thismanuscript our aim is to offer a global view of the centres and connections that play the most significant roles in the formationof taste aversion learning (TAL). Conclusions. Many researchers consider that the initial level of integration is situated withinthe parabrachial nuclei. A priori and given the basic vital nature of TAL, its formation and completion could be thought to takeplace at this brain stem level, without requiring the intervention of the higher processing structures. Nevertheless, in theliterature on TAL there is a large body of both neuroanatomical and neurobehavioural evidence that seems to indicate that theformation of TAL requires complex interactions between the parabrachial nuclei and certain prosencephalic structures, suchas the insular cortex or the amygdala, among others
Asunto(s)
Animales , Humanos , Reacción de Prevención/fisiología , Condicionamiento Clásico/fisiología , Gusto , Amígdala del Cerebelo/anatomía & histología , Amígdala del Cerebelo/fisiología , Vías Nerviosas/fisiología , Puente/anatomía & histología , Puente/fisiología , Núcleo Solitario/anatomía & histología , Núcleo Solitario/fisiologíaRESUMEN
El sueño lento es una previa condición para la normal expresión del sueño paradójico (SP). El tronco encefálico bajo es reponsable de los fenómenos que se asocian con el SP, pero para lograrlo en toda su magnitud funcional, esta zona depende del resto del encéfalo. Para el desarrollo del SP aparecen como necesarias ciertas funciones básicas, i.e., respiratorias, cardiovasculares, disponibilidad de oxígeno cerebral local, temperatura, etc., deberán funcionar en condiciones de n-homeostasis durante este estado. Otras condiciones a cumplirse son la eliminación de la salida motora y un control del ingreso sensorial diferente. Durante el SP se observan cambios fásicos de la pO2 en estructuras nucleares caracterizados por un dramático aumento en la amplitud de las oscilaciones. Estos cambios se encontraron en regiones subcorticales, cerebelo y tronco cerebral. No se obtuvieron en núcleos talámicos específicos, en la corteza ni en la sustancia blanca. Se postula que estas variaciones son debidas al incremento de la actividad neuronal en el SP y que ocurre en un período de disminución del control homeostático del oxígeno en el tejido cerebral. Todos los cambios mencionados tienen un denominador común anatómico: la protuberancia y el bulbo. Sobre esta zona, que se propone como una REGION FINAL COMUN para el SP, converge información rostral y caudal, haciendo de ella la región ejecutora de la fenomenología del SP. Por otra parte, la protuberancia tiene actividad bioeléctrica propia durante el SP, i.e., las puntas ponto-genículo-occipitales (PGO). Estas puntas se propagan al cerebro y al cerebelo. Este último también participa de la pO2 y las PGO han sido descritas en su corteza y núcleos. La actividad PGO del cerebelo es tambiém dependiente de una zona colinérgica pontina. La protuberancia muestra, entonces, una dualidad particular durante el SP. Forma parte de la REGION FINAL COMUN y, al mismo tiempo, es el origen de la actividad PGO (AU)
Asunto(s)
Animales , Cerebro/fisiología , Sueño REM/fisiología , Cerebelo/fisiología , Puente/fisiologíaRESUMEN
El sueño lento es una previa condición para la normal expresión del sueño paradójico (SP). El tronco encefálico bajo es reponsable de los fenómenos que se asocian con el SP, pero para lograrlo en toda su magnitud funcional, esta zona depende del resto del encéfalo. Para el desarrollo del SP aparecen como necesarias ciertas funciones básicas, i.e., respiratorias, cardiovasculares, disponibilidad de oxígeno cerebral local, temperatura, etc., deberán funcionar en condiciones de n-homeostasis durante este estado. Otras condiciones a cumplirse son la eliminación de la salida motora y un control del ingreso sensorial diferente. Durante el SP se observan cambios fásicos de la pO2 en estructuras nucleares caracterizados por un dramático aumento en la amplitud de las oscilaciones. Estos cambios se encontraron en regiones subcorticales, cerebelo y tronco cerebral. No se obtuvieron en núcleos talámicos específicos, en la corteza ni en la sustancia blanca. Se postula que estas variaciones son debidas al incremento de la actividad neuronal en el SP y que ocurre en un período de disminución del control homeostático del oxígeno en el tejido cerebral. Todos los cambios mencionados tienen un denominador común anatómico: la protuberancia y el bulbo. Sobre esta zona, que se propone como una REGION FINAL COMUN para el SP, converge información rostral y caudal, haciendo de ella la región ejecutora de la fenomenología del SP. Por otra parte, la protuberancia tiene actividad bioeléctrica propia durante el SP, i.e., las puntas ponto-genículo-occipitales (PGO). Estas puntas se propagan al cerebro y al cerebelo. Este último también participa de la pO2 y las PGO han sido descritas en su corteza y núcleos. La actividad PGO del cerebelo es tambiém dependiente de una zona colinérgica pontina. La protuberancia muestra, entonces, una dualidad particular durante el SP. Forma parte de la REGION FINAL COMUN y, al mismo tiempo, es el origen de la actividad PGO