Control of Cortical Inputs to the Ventral Striatum by Dopamine: Effects on Weak and Strong Inputs

Grant Type
Grant Year
Institution Location
Institution Organization Name
Albany Medical College
Investigators Name
Gruber, Aaron, PhD

Many medications used in the treatment of TS target dopamine transmission. However, the mechanisms by which these drugs inhibit unwanted motor and cognitive activity are poorly understood. A better understanding may be an important step for the development of more effective treatments. The link between dopamine and the phenomenology of TS is obscured not only by the complexity of dopaminergic actions in the brain, but also by our rudimentary understanding of how information is processed in brain regions involved in the planning of movements. Two key neural regions are the prefrontal cortex and the basal ganglia, which are thought to be important for both planning desired movements and also for inhibiting unwanted actions. This project will investigate how signals from the cortex are processed in the nucleus accumbens, an important input region of the basal ganglia, and how this processing is affected by dopamine. The focus will be to investigate how dopamine and local inhibition in the accumbens shape the responses to bursting cortical inputs. In particular, this project will test the popular view that dopamine enhances neural processing by selectively suppressing weak ‘noise-related’ activity while allowing strong ‘signal-related’ activity to persist. An imbalance in this process of selective suppression of neural activity may play a role in the motor tics associated with TS. The ability of dopamine to shape neural responses in the accumbens may be altered by drugs that target dopamine receptors, such as D2 receptor antagonists used to aid the suppression of tics in TS. The effects of this class of drug on the activity in the accumbens will be explored in an attempt to link the administration of clinically useful drugs to an alteration in neuronal signaling. Aaron J. Gruber, Ph.D. Albany Medical College, Albany, New York Award: $38,000 In Memory of Jackie Aron for Her Generous and Long-Time Support of the Tsa Research Program Tourette Association of America Inc. – Research Grant Award 2005-2006