KRISTEN KEEFE

My research was focused on the structure and function of the basal ganglia, a group of subcortical nuclei in the brain involved in the control of movement and cognition. The importance of the basal ganglia for normal behavior is highlighted by the profound deficits observed in patients with Parkinson's disease, Huntington's disease, schizophrenia, and drug addiction -- diseases that are associated with dysfunction in the basal ganglia.

Our work has determined the influence of both endogenous and exogenous chemicals on the function of neurons in the basal ganglia in an attempt to better understand 1) the role that glutamate (via NMDA receptors) and monoamines (dopamine and serotonin) play in regulating the activity of basal ganglia nuclei, 2) the mechanisms by which drugs of abuse that affect the basal ganglia exert both their acute and long-lasting adverse effects, and 3) the mechanisms by which the function of the basal ganglia can be beneficially altered by drugs to better treat sequelae associated with dysfunction in these nuclei.

We have used numerous techniques to examine the effects of both endogenous and exogenous drugs on basal ganglia function. These techniques include: 1) In vivo microdialysis in the brain of awake animals to examine changes in the release of amino acid, monoamine, and neuropeptide neurotransmitters. 2) In situ hybridization histochemistry to measure changes in the levels of messenger RNAs in brain neurons to examine short- and long-term changes in gene expression in neurons of the basal ganglia. 3) Immunohistochemistry to examine changes in protein expression in defined basal ganglia neurons and nuclei. 4) Behavioral analyses of learning and memory processes mediated by corticostriatal circuits. Coupling these techniques, we begin to understand how neurotransmitters and drugs acutely affect the function of basal ganglia neurons and the neuroadaptive changes that occur in response to neural injury in the basal ganglia and exposure to therapeutic and abused drugs.