Your browser doesn't support javascript.
loading
Mostrar: 20 | 50 | 100
Resultados 1 - 2 de 2
Filtrar
Más filtros










Base de datos
Intervalo de año de publicación
1.
Elife ; 82019 09 09.
Artículo en Inglés | MEDLINE | ID: mdl-31498083

RESUMEN

Most of our knowledge on human CNS circuitry and related disorders originates from model organisms. How well such data translate to the human CNS remains largely to be determined. Human brain slice cultures derived from neurosurgical resections may offer novel avenues to approach this translational gap. We now demonstrate robust preservation of the complex neuronal cytoarchitecture and electrophysiological properties of human pyramidal neurons in long-term brain slice cultures. Further experiments delineate the optimal conditions for efficient viral transduction of cultures, enabling 'high throughput' fluorescence-mediated 3D reconstruction of genetically targeted neurons at comparable quality to state-of-the-art biocytin fillings, and demonstrate feasibility of long term live cell imaging of human cells in vitro. This model system has implications toward a broad spectrum of translational studies, regarding the validation of data obtained in non-human model systems, for therapeutic screening and genetic dissection of human CNS circuitry.


Asunto(s)
Encéfalo/anatomía & histología , Encéfalo/fisiología , Técnicas de Cultivo de Órganos/métodos , Adulto , Encéfalo/patología , Encéfalo/fisiopatología , Humanos , Microscopía Intravital/métodos , Células Piramidales/patología , Células Piramidales/fisiología
2.
J Neurophysiol ; 121(4): 1102-1110, 2019 04 01.
Artículo en Inglés | MEDLINE | ID: mdl-30699003

RESUMEN

Doxapram is a respiratory stimulant used for decades as a treatment option in apnea of prematurity refractory to methylxanthine treatment. Its mode of action, however, is still poorly understood. We investigated direct effects of doxapram on the pre-Bötzinger complex (PreBötC) and on a downstream motor output system, the hypoglossal nucleus (XII), in the transverse brainstem slice preparation. While doxapram has only a modest stimulatory effect on frequency of activity generated within the PreBötC, a much more robust increase in the amplitude of population activity in the subsequent motor output generated in the XII was observed. In whole cell patch-clamp recordings of PreBötC and XII neurons, we confirmed significantly increased firing of evoked action potentials in XII neurons in the presence of doxapram, while PreBötC neurons showed no significant alteration in firing properties. Interestingly, the amplitude of activity in the motor output was not increased in the presence of doxapram compared with control conditions during hypoxia. We conclude that part of the stimulatory effects of doxapram is caused by direct input on brainstem centers with differential effects on the rhythm generating kernel (PreBötC) and the downstream motor output (XII). NEW & NOTEWORTHY The clinically used respiratory stimulant doxapram has distinct effects on the rhythm generating kernel (pre-Bötzinger complex) and motor output centers (nucleus hypoglossus). These effects are obliterated during hypoxia and are mediated by distinct changes in the intrinsic properties of neurons of the nucleus hypoglossus and synaptic transmission received by pre-Bötzinger complex neurons.


Asunto(s)
Tronco Encefálico/efectos de los fármacos , Estimulantes del Sistema Nervioso Central/farmacología , Doxapram/farmacología , Nervio Hipogloso/efectos de los fármacos , Neuronas Motoras/efectos de los fármacos , Fármacos del Sistema Respiratorio/farmacología , Potenciales de Acción , Animales , Tronco Encefálico/citología , Tronco Encefálico/fisiología , Generadores de Patrones Centrales/citología , Generadores de Patrones Centrales/efectos de los fármacos , Generadores de Patrones Centrales/fisiología , Femenino , Nervio Hipogloso/citología , Nervio Hipogloso/fisiología , Masculino , Ratones , Neuronas Motoras/fisiología , Respiración
SELECCIÓN DE REFERENCIAS
DETALLE DE LA BÚSQUEDA
...