In vivo optogenetics to distinguish learning from performance effects of dopamine on fine motor skills

2014 Seed Grant
Daniel Leventhal, Ph.D.
Department of Neurology
University of Michigan

Parkinson Disease (PD) is a common, disabling condition characterized by progressive slowness of movement and loss of the brain chemical dopamine. Though it has been known for more than 40 years that replacing dopamine improves motor function, we still do not understand why. Ideas regarding the role of dopamine in motor control can be broadly divided into “performance” and “learning” categories. That is, the presence or absence of dopamine may influence movement at that moment (“performance”) or in the future (“learning”). It has been hard to tease these possibilities apart because techniques to alter dopamine signaling in the brain (for example, drugs) act on long timescales. We will overcome this using optogenetic techniques, where individual nerve cells (in this case, dopamine cells) can be turned on or off with millisecond precision by light pulses. By turning dopamine neurons off at key moments as rats perform skilled reaching movements, we will determine how the timing of dopamine signaling influences the performance and acquisition of fine motor skills. By better understanding how dopamine influences motor learning and performance, therapies can be more rationally designed to improve efficacy and reduce side-effects of treatment for PD.