SMILE · Study of the molecular and cellular mechanisms of incentive learning

Incentive learning is a universal mechanism by which animals and humans learn rewarding behavioral responses. Its diversion towards the wrong targets is involved in human conditions ranging from drug addiction to pathological gambling and obesity. Incentive learning has been studied from a behavioral standpoint and only few of the underlying molecular mechanisms have been identified. We propose innovative approaches to characterize at the molecular and cellular level incentive memory traces , i.e. stable alterations in identified neuronal populations. We focus on the striatum, a brain region crucial for incentive learning, where dopamine encodes reward-related signals. Dopamine controls the flow of information through glutamatergic synapses and its long-lasting adaptations. It regulates the balance between striatal output pathways, which underlies action selection , i.e. behavioral choices in response to a given combination of internal state and external cues and context. We will address two important issues: What are the signaling mechanisms involved in the formation and reconsolidation of incentive memory traces induced by DA and glutamate? In which neuronal populations are these traces formed and what are their time-dependent modifications? The program uses a variety of approaches including novel mouse genetic models and approaches for visualizing striatal neurons in vivo. If successful, these methods have a strong potential for more general applicability. This basic research program will allow the identification of the molecular and cellular mechanisms of a simple learning mechanism with an unprecedented precision and will provide important information related to its alterations in neurological and psychiatric conditions, including addiction.