Motivational deficits accompany a wide range of neurological and psychiatric disorders including Parkinson's Disease, Depression, and Schizophrenia. To gain a more complete understanding of these motivational deficits, it is necessary to the study brain circuitry that stands at the interface of motivation and action. Motivation and movement are intimately linked. In healthy animals, decision costs and benefits have been shown to decrease or increase the speed or vigor of action execution. The basal ganglia and dopaminergic neurons in the midbrain have been implicated in this process, but their precise roles are still unclear. The goal of this study is to examine how costs and benefits are integrated in subcortical dopamine and basal ganglia circuitry, and to understand how integration of these motivational variables shape motor responses. The basal ganglia is comprised of two major circuits, the direct and indirect pathways, which are thought to have opposing effects on movement. However, it is still not well known how these circuits encode positive and negative motivational information and how this may modulate motor responses. In addition, we know little about how dopaminergic innervation in different regions of the basal ganglia contribute to this process. To gain a better understanding of the circuit mechanisms underlying motivated behavior, we developed a novel set of tasks for mice that allows for quantitative dissection of the effects of effort and reward magnitude on response vigor. We will employ the use of the latest cutting-edge techniques for recording single-cell activity from identified cell types and for recording the activity of anatomically-defined projection targets to determine how dopaminergic and basal ganglia circuits transform motivational variables into action. My long-term career goal is to study the computational role of circuits involved in learning and decision making, with a specific interest in how information processing is impaired in psychiatric disorders. The Gladstone Institutes and broader environment at UCSF provide a unique emphasis on both translational and basic science approaches to understanding psychiatric disease. I plan to take advantage of the full range of career development opportunities that are offered for young investigators. These include speaking opportunities at internal retreats, taking scientific leadership and management courses, and attending seminars related to grant writing and mentoring that are specifically tailored for postdoctoral scholars seeking research independence.
A number of neurological and psychiatric disorders, such as Parkinson's disease and Schziophrenia, have been associated with profound motivational deficits, including anergia and psychomotor slowing. Intact functioning of dopaminergic neurons in the midbrain and circuitry in the basal ganglia are critical for normal motor function, but we still know little about how these structures transform motivational information into action. We will use the latest cutting edge techniques to study this process in order to provide insight on the circuit mechanisms underlying these motivational deficits.
