Descripción del proyecto
Comprender el comportamiento compulsivo: la influencia del cuerpo estriado
El cuerpo estriado, uno de los principales componentes de los ganglios basales, facilita la planificación, preparación y ejecución del movimiento voluntario tras recibir información de la corteza cerebral. El proyecto CoordinatedDopamine, financiado por el Consejo Europeo de Investigación, tiene como objetivo investigar el modo en que se comunican las unidades funcionales límbicas y sensoriomotoras del cuerpo estriado para conseguir la automatización de secuencias de acción. Los investigadores estudiarán una hipótesis de vinculación entre estas dos estructuras facilitada por las neuronas dopaminérgicas. Para ello, utilizarán electrodos implantados que les permitan medir la liberación de dopamina en animales, junto con otras técnicas de administración génica destinadas a explorar vías cerebrales específicas. Los resultados aportarán información importante sobre la ejecución compulsiva de acciones automáticas que se observa en los trastornos psiquiátricos.
Objetivo
The basal ganglia consist of a set of neuroanatomical structures that participate in the representation and execution of action sequences. Dopamine neurotransmission in the striatum, the main input nucleus of the basal ganglia, is a fundamental mechanism involved in learning and regulation of such actions. The striatum has multiple functional units, where the limbic striatum is thought to mediate motivational aspects of actions (e.g. goal-directedness) and the sensorimotor striatum their automation (e.g. habit formation). A long-standing question in the field is how limbic and sensorimotor domains communicate with each other, and specifically if they do so during the automation of action sequences. It has been suggested that such coordination is implemented by reciprocal loop connections between striatal projection neurons and the dopaminergic midbrain. Although very influential in theory the effectiveness of this limbic-sensorimotor “bridging” principle has yet to be verified. I hypothesize that during the automation of behaviour regional dopamine signalling is governed by a striatal hierarchy and that dysregulation of this coordination leads to compulsive execution of automatic actions characteristic of several psychiatric disorders. To test this hypothesis, we will conduct electrochemical measurements with real-time resolution simultaneously in limbic and sensorimotor striatum to assess the regional coordination of dopamine release in behaving animals. We developed novel chronically implantable electrodes to enable monitoring of dopamine dynamics throughout the development of habitual behaviour and its compulsive execution in transgenic rats - a species suitable for our complex behavioural assays. Novel rabies virus-mediated gene delivery for in vivo optogenetics in these rats will give us the unique opportunity to test whether specific loop pathways govern striatal dopamine transmission and are causally involved in habit formation and compulsive behaviour.
Ámbito científico
Programa(s)
Régimen de financiación
ERC-STG - Starting GrantInstitución de acogida
1105AZ Amsterdam
Países Bajos