Description du projet
Comprendre les comportements compulsifs: l’influence du striatum
La planification, la préparation et l’exécution des mouvements volontaires sont facilitées par le striatum, l’un des principaux composants des ganglions de la base, qui reçoit des informations du cortex cérébral. Financé par le Conseil européen de la recherche, le projet CoordinatedDopamine vise à étudier comment les unités fonctionnelles limbiques et sensorimotrices du striatum communiquent pour l’automatisation des séquences d’actions. Les chercheurs étudieront l’hypothèse d’un lien entre ces deux structures, activé par les neurones dopaminergiques. Pour ce faire, ils utiliseront des électrodes implantées pour mesurer la libération de dopamine chez les animaux qui se comportent correctement, et des techniques d’insertion de gènes pour analyser des voies cérébrales spécifiques. Les résultats fourniront des informations importantes sur l’exécution compulsive d’actions automatiques observée dans les troubles psychiatriques.
Objectif
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.
Champ scientifique
Programme(s)
Thème(s)
Régime de financement
ERC-STG - Starting GrantInstitution d’accueil
1105AZ Amsterdam
Pays-Bas