Real-time G-protein-coupled receptor imaging to understand and quantify receptor dynamics.

Understanding the trafficking of G-protein-coupled receptors (GPCRs) and their regulation by agonists and antagonists is fundamental to develop more effective drugs. Optical methods using fluorescent-tagged receptors and spinning disk confocal microscopy are useful tools to investigate membrane receptor dynamics in living cells. The aim of this study was to develop a method to characterize receptor dynamics using this system which offers the advantage of very fast image acquisition with minimal cell perturbation. However, in short-term assays photobleaching was still a problem. Thus, we developed a procedure to perform a photobleaching-corrected image analysis. A study of short-term dynamics of the long isoform of the dopamine type 2 receptor revealed an agonist-induced increase in the mobile fraction of receptors with a rate of movement of 0.08 µm/s For long-term assays, the ratio between the relative fluorescence intensity at the cell surface versus that in the intracellular compartment indicated that receptor internalization only occurred in cells co-expressing G protein-coupled receptor kinase 2. These results indicate that the lateral movement of receptors and receptor internalization are not directly coupled. Thus, we believe that live imaging of GPCRs using spinning disk confocal image analysis constitutes a powerful tool to study of receptor dynamics.

Oscilaciones cerebrales: papel fisiopatológico y terapéutico en algunas enfermedades neurológicas y psiquiátricas / Brain oscillations: pathophysiological and therapeutic role in some neurological and psychiatric diseases

Se usa el término «oscilación o actividad oscilatoria» para referirse a las fluctuaciones rítmicas de los potenciales postsinápticos de un grupo neuronal (potenciales de campo local) o de una región cortical (EEG, electrocorticografía) y también al patrón de descarga rítmico de los potenciales de acción de una neurona o un grupo neuronal. La actividad oscilatoria posibilita la sincronización entre grupos neuronales de la misma área cortical o de áreas distantes entre sí que intervienen en una acción motora, tarea cognitiva o perceptiva. Con frecuencia es motivo de confusión asociar la presencia de actividad oscilatoria con fenómenos de sincronización, ya que ambos fenómenos aunque relacionados no son equivalentes. En patologías neurológicas o psiquiátricas tan distintas como la enfermedad de Parkinson u otros movimientos anormales, la epilepsia o la esquizofrenia se han descrito anomalías de la actividad oscilatoria de distintas estructuras cerebrales o de su sincronización que podrían jugar un papel relevante en su fisiopatología. En esta revisión se discuten estos aspectos haciendo hincapié en su importancia por ser un mecanismo básico del funcionamiento cerebral y un nuevo mecanismo fisiopatólogico de la sintomatología de algunas enfermedades cerebrales (AU)

The terms «oscillations» or «oscillatory activity» are frequently used not only to define the rhythmic fluctuations of the postsynaptic potentials of a neuronal group (local field potentials) or a cortical region (EEG, MEG), but also to indicate the rhythmic discharge pattern of action potentials from a neuron or a small group of neurons. Oscillatory activity makes possible the synchronization of different neuronal groups from nearby or distant cortical regions that participate in the same motor, sensory or cognitive task. The presence of oscillatory activity is usually associated to the existence of synchronization, but both phenomena are not necessarily always equivalent. Abnormalities of oscillatory activities or synchronization within or between different brain structures have been described in several neurological and psychiatric diseases; these abnormalities might play a relevant pathophysiological role in Parkinson´s disease (and other movement disorders), schizophrenia or epilepsy. This review discusses all these aspects, with emphasis on their potential role both as a basic mechanism in brain function and as a pathophysiological substrate for some of the symptoms and signs observed in several diseases (AU)