Research Interests

Our research focuses on the functional organization of the basal ganglia and related brain systems, especially on the role of the neurotransmitter dopamine in the regulation of basal ganglia - cortical interactions. One of the main objectives is to understand how pathologically altered activities in transmitter systems such as dopamine cause neuroadaptive changes in neurons of the basal ganglia and their functional consequences. Current projects investigate how chronic enhancement of dopamine actions [e.g., by psychostimulants such as cocaine and methylphenidate (Ritalin)], or their attenuation (e.g., by antipsychotic drugs or dopamine depletion), produce changes in gene regulation, and how these molecular alterations affect basal ganglia function and behavior. Genes encoding neuropeptide transmitters (e.g., opioid peptides), enzymes, receptors, ion channels, transcription factors, and other plasticity-associated molecules are of primary interest. Some of the current studies investigate drug effects on molecular and cellular mechanisms of motor learning.

These questions are mainly studied in the following animal models: 1) repeated treatment with dopamine agonists (e.g., psychostimulants) or antagonists (e.g., antipsychotics) in rats; 2) dopamine depletion by neurotoxins (models for Parkinson's disease) in rats; and 3) in mice with null mutations for specific receptors or neuropeptides (gene knockouts). Gene expression is measured with quantitative in situ hybridization histochemistry in combination with autoradiography and immunohistochemical techniques. Other experimental approaches include anatomical techniques (e.g., tract tracing, ultrastructural imaging) and electrophysiological methods (in collaboration). In many of our studies, molecular/cellular and behavioral effects are measured in parallel for correlation analyses.