Determining modes of dopamine transmission

Project Summary Dopamine system is a key neuromodulator that plays multiple roles in regulating locomotion, activity and motor learning within the striatum. As such dysfunctions in dopamine signaling arise in multiple neurological disorders such as Parkinson’s disease. Despite a wealth of literature at the circuit, system and behavioral level it still remains unknown how dopamine signals mediate transmission and how potentially different signals drive different aspects of motor function and learning. To address this the current proposal will use several novel approaches to examine if different dopamine signals exist and if they do what role they may play in gross motor output and motor learning. By altering different aspects of dopamine release and transmission this application will measure local receptor mediated signals as well as quantify bulk spillover dopamine to determine if both aspects are equally perturbed by these manipulations. These different animal models will also be used to see how these perturbations may alter different aspects of gross motor output and motor learning. These experiments will test the central hypothesis that striatal dopamine signals that underlie synaptic vs spillover can be independently regulated and that each regulate different aspects of dopamine’s behavioral functions. The significance of this work will be to determine how dopamine dynamics drive the activation of dopamine receptors to mediate transmission and to determine how those dynamics directly participate in regulating striatal circuits to drive motor activity and motor learning. The proposed studies are expected to be significant in that insights in to the specific mechanisms that regulate dopamine transmission, and are expected to directly lead to testable hypothesis regarding the dysregulations in this system that occur following the loss of dopamine in neurological disorders such as Parkinson’s disease.