Molecular Mechanisms Regulating Interneuron Expression of Parvalbumin

Grant Type
Basic
Grant Year
2006-2007
Institution Location
MD
Institution Organization Name
University of Maryland
Investigators Name
Powell, Elizabeth, PhD

Many medications used in the treatment of TS target dopamine transmission. However, the mechanisms by which these drugs help inhibit unwanted motor and cognitive activities are poorly understood. The link between dopamine and the phenomenology of TS is obscured not only by the complexity of dopamine’s actions in the brain, but also by our rudimentary understanding of how information is processed in brain regions involved in making decisions and planning movements. Two key neural regions for these functions are the prefrontal cortex and the basal ganglia. 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. A novel component of the project is that electrical stimulation is used to activate the cortex in a pattern similar to natural activation associated with detection of stimuli and the generation of movements. In last year’s TSA funded study we found that the response of the neurons in the nucleus accumbens to this more natural input pattern depends on many stimulation features, and that a prominent inhibitory component regulates the activity of these neurons. The current focus of the project is to explore how dopamine and local inhibition in the nucleus accumbens control the responses to the input. Specifically, this project is designed to test the popular view that dopamine, and possibly inhibitory interneurons, enhance neural processing by selectively suppressing weak “noise-related” activity while allowing strong “signal-related” activity to persist. An imbalance in this process 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 frequently used to suppress tics. The effects of this class of drug on the neural activity in the accumbens will be explored in an attempt to link the administration of clinically useful drugs to an alteration in neuronal signaling. Elizabeth M. Powell, Ph.D. University of Maryland, School of Medicine, Baltimore, Maryland Award: $75,000 Tourette Association of America Inc. – Research Grant Award 2006-2007