Kristen A. Keefe
Professor of Pharmacology and Toxicology
Brain and Behavior
Neurobiology of Disease
B.S. 1984, Case Western Reserve University; M.S. 1989, University of Pittsburgh; Ph.D. 1992, University of Pittsburgh; Post-doctoral fellow 1992-1995, NIMH
Pharmacology of neurological and neuropsychiatric disorders, including drug abuse and addiction. Normal and pathological functions of the basal ganglia
My laboratory is interested in the functional neuroanatomy of the basal ganglia, a group of subcortical nuclei in the brain involved in the control of movement and cognition, including habit formation and procedural learning. 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 determines 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 produce long-term alterations in basal ganglia function, 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 use numerous techniques to examine basal ganglia function including: 1) in vivo microdialysis; 2) in situ hybridization histochemistry; 3) immunohistochemistry; 4) in vitro, whole-cell patch-clamp electrophysiology; 5) behavioral analyses.
Coupling these techniques, we can 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.