RESUMEN
BACKGROUND AND OBJECTIVES: Several cognitive event-related potential (ERP) components such as mismatch negativity, P300, N400, and the late positive component (LPC) have been studied in aphasia. The aim of this study was to determine whether a modified semantic incongruity paradigm can serve as a more graded differentiation of ERP changes in patients with mild versus severe comprehension deficits. METHODS: A total of 20 aphasic patients with minor and severe comprehension deficits and 20 young and elderly healthy controls were examined while reading 4-word sentences ending in a semantically congruent or noncongruent word. RESULTS: In contrast to young controls and to patients with mild comprehension deficits, aphasic patients with severe comprehension deficits exhibit an early positivity in the time window from 200 to 400 milliseconds and no N400 after the presentation of nonrecurrent semantically incongruent words. Patients with mild comprehension deficits were found to have an N400 with prolonged latency in comparison with the controls. An age effect in the control groups was detected as well. DISCUSSION: Semantic access and integration are performed differently in aphasic subjects with severe comprehension deficits. These differences in lexical-semantic processing must be taken into account in rehabilitation approaches that aim to improve comprehension deficits. Moreover, the findings may contribute to the design of therapy studies by employing a physiological measure that can discriminate among patients at baseline and at the end of an intervention.
Asunto(s)
Afasia/fisiopatología , Encéfalo/fisiopatología , Comprensión , Potenciales Evocados , Adulto , Factores de Edad , Afasia/etiología , Mapeo Encefálico/métodos , Dominancia Cerebral , Electroencefalografía , Femenino , Humanos , Pruebas del Lenguaje , Masculino , Persona de Mediana Edad , Tiempo de Reacción , Lectura , Semántica , Índice de Severidad de la Enfermedad , Accidente Cerebrovascular/complicaciones , Accidente Cerebrovascular/fisiopatologíaRESUMEN
In the retina, chemical and electrical synapses couple neurons into functional networks. New candidates encoding for electrical synapse proteins have recently emerged. In the present study, we determined the localization of the candidate protein pannexin1 (zfPanx1) in the zebrafish retina and studied the functional properties of zfPanx1 exogenously expressed in Neuroblastoma 2a (N2a) cells. zfPanx1 was identified on the surface of horizontal cell dendrites invaginating deeply into the cone pedicle near the glutamate release sites of the cones, providing in vivo evidence for hemichannel formation at that location. This strategic position of zfPanx1 in the photoreceptor synapse could potentially allow modulation of cone output. Using whole cell voltage clamp and excised patch recordings of transfected N2a cells, we demonstrated that zfPanx1 forms voltage-activated hemichannels with a large unitary conductance in vitro. These channels can open at physiological membrane potentials. Functional channels were not formed following mutation of a single amino acid within a conserved protein motif recently shown to be N-glycosylated in rodent Panx1. Together, these findings indicate that zfPanx1 displays properties similar to its mammalian homologues and can potentially play an important role in functions of the outer retina.
Asunto(s)
Conexinas/biosíntesis , Canales Iónicos/biosíntesis , Segmento Externo de las Células Fotorreceptoras Retinianas/metabolismo , Proteínas de Pez Cebra/biosíntesis , Pez Cebra/metabolismo , Animales , Calcio/metabolismo , Línea Celular Tumoral , Conexinas/genética , Dendritas/metabolismo , Uniones Comunicantes/metabolismo , Espacio Intracelular/metabolismo , Activación del Canal Iónico , Potenciales de la Membrana , Ratones , Técnicas de Placa-Clamp , Segmento Externo de las Células Fotorreceptoras Retinianas/ultraestructura , Proteínas de Pez Cebra/genéticaRESUMEN
Pannexins (Panx) constitute a new family of gap junction type proteins. Functional expression in paired Xenopus oocytes indicated that pannexins are capable of forming communicating junctions but also proved to be active in forming of unopposed hemichannels. In the vertebrate brain pannexins have been found in neurons. However, the subcellular cerebral localization of pannexin proteins which could gain first clues on their putative function is essentially unknown. Here we demonstrate by light and electron microscopical immunohistochemistry that Panx1 reveals postsynaptic localization in rodent hippocampal and cortical principal neurons accumulating at postsynaptic densities. The postsynaptic localization was corroborated by co-localization of Panx1 with postsynaptic density protein 95 (PSD-95), a prominent postsynaptic scaffolding protein, in hippocampal neurons expressing tagged versions of these proteins. The asymmetric synaptic distribution of Panx1 suggests that it may function in neurons as non-junctional channels (pannexons) at postsynaptic sites and comprises a novel component of the postsynaptic protein complex.