Konstantinos Meletis

Action selection, decision-making and cognitive flexibility are critical brain functions for humans and other animals in order to thrive and survive in a complex environment. The frontal cortex and the basal ganglia are thought to control selection of appropriate actions, evaluate their outcome, and update behaviors accordingly. Degeneration of the dopamine system is a hallmark of Parkinson’s disease (PD), and in the prodromal phases of the disease, cognitive and emotional behaviors are affected before the emergence of severe motor dysfunction. We hypothesize that motor and non-motor/motivated behaviors are shaped by the activity of distinct dopamine subtypes, where discrete aspects of motivated behaviors are regulated by different dopamine neuron subtypes and their interactions with striatal compartments and neuron types. In this project, we will investigate the function of Anxa1+ dopamine neurons for learning new motor skills, particularly fine motor actions like reaching and grasping, and cognitive flexibility during choice tasks – and define their role in the manifestation of cognitive and motor learning impairments in prodromal PD. Our aim is to define how specialized interactions between neurons subtypes in the dopamine system and the striatum control motivated behaviors and learning, with the long-term aim to establish a mechanistic understanding of how the organized connectivity between molecularly defined subregions and neuron types shapes complex behaviors.