Graduate Studies Faculty
Kari J. Buck, Ph.D.
Neuroscience Graduate Program
Research Interests:Neuroscience. Genetic predisposition to alcohol and drug self-administration, learning and reward, dependence and withdrawal. State-of-the-art genetic animal models (e.g., transgenic and RNAi) and molecular approaches to elucidate genetic determinants of these behaviors and therapeutic targets. These include genetic determinants of mitochondrial function and oxidative stress, G-protein receptor activated potassium (GIRK) channel function in response to G-protein receptor activation, and the multiple PDZ domain protein (MPDZ/MUPP1) and its regulation of GABA-B, NMDA-AMPA and serotonin receptor mediated signal transduction. » PubMed Listing
Preceptor RotationsAcademic Term Available Winter 2014 Yes Spring 2014 Yes Fall 2015 Yes Summer 2015 Yes Fall 2014 Yes Spring 2015 Yes Winter 2015 Yes Summer 2016 Yes Fall 2016 Yes Winter 2016 Yes Spring 2016 Yes Summer 2017 Yes Fall 2017 Yes Winter 2017 Yes Spring 2017 Yes
Faculty MentorshipDr. Buck is available as a mentor for 2013-2014. Dr. Buck is available as a mentor for 2014-2015.
- The identification of translational genes involved in drug and alcohol reward and the negative consequence of their abuse.
- The identification of the brain neural pathways by which these genes affect drug and alcohol reward, dependence, and withdrawal.
- Rigorous testing of all of the above using novel genetic methods (e.g., RNA interference, knockout and transgenic animal models).
- The application of these approaches to current and future translational genes/proteins (e.g., Mpdz/MUPP1, Kcnj9/GIRK3).
- A new direction of the role mitochondrial function and oxidative stress in alcohol reward (CPP), dependence, and withdrawal.
Summary of Current Research
A host of biological (genetic) and environmental factors interact in a complex manner throughout the addictive process to influence drug and alcohol use/abuse and contribute to relapse. My research uses preclinical (animal) models that closely approximate aspects of the human clinical situation to elucidate the gene and neural networks involved in drug response. We utilize robust behavioral models of drug and alcohol reward (e.g., conditioned place preference (CPP) and voluntary consumption phenotypes), dependence, and withdrawal (e.g., anxiety and depression-like behaviors, brain excitability/seizures). We use state-of-the-art approaches (e.g., RNA interference, stereotaxic site-directed pharmacological manipulations) to identify and rigorously test the role of specific genes (often referred to as quantitative trait loci/genes), larger gene networks (e.g., involved in oxidative stress, and a network involved in G-protein coupled receptor mediated signaling), brain regions, and pathways (e.g., limbic and basal ganglia, including amygdala, striatum, anterior cingulate cortex, substantia nigra, and hippocampus) in drug and alcohol response (e.g., sedative and euphoric actions), reward, dependence, and withdrawal. In collaboration with Behavioral Neuroscience faculty we also use neuroelectrophysiological approaches.
Kruse L and Buck KJ (2014). MPDZ RNA interference in the caudolateral substantia nigra reticulata mitigates ethanol withdrawal in mice. Under review.
Milner LC, Shirley RL, Kozell LB, Walter NA, Kruse LC, Komiyama NH, Grant SGN, Buck KJ (2013-4: doi 2013). Novel MPDZ/MUPP1 transgenic and knockdown models confirm Mpdz's role in ethanol withdrawal and support its role in voluntary ethanol consumption. Addiction Biology. (Dec 2013 doi: 10.1111/adb.12087).
Buck KJ, Walter NAR, and Denmark DL (2013). Genetic variability of respiratory complex abundance, organization, and activity in mouse brain. Genes Brain Behavior. (Oct 2013 doi: 10.1111/gbb.12101).
López-Jiménez A, Walter NAR, Giné E, Santos A, Echeverry-Alzate V, Giezendanner S, Sainz L, Moratalla R, Montoliu L, Buck KJ, Lopez-Moreno JA (2013). A spontaneous deletion of alpha-synuclein is associated with an increase in CB1 mRNA transcript and receptor expression in the hippocampus and amygdala; effects on alcohol consumption. Synapse 67:280-289.
Bottomly D, Walter NA, Hunter JE, Darakjian P, Kawane S, Buck KJ, Searles RP, Mooney M, McWeeney SK, Hitzemann R (2011) Evaluating gene expression in C57BL/6J and DBA/2J mouse striatum using RNA-seq and microarrays. PLoS One Mar 24; 6(3):e17820.
Chen G and Buck KJ (2010) Rostroventral caudate putamen involvement in ethanol withdrawal is influenced by a chromosome 4 locus. Genes Brain and Behavior. 9:768-776.
Ehlers CL, Walter NAR, Dick D, Buck KJ, Crabbe JC (2010). A comparison of selected quantitative trait loci associated with alcohol use phenotypes in humans and mouse models. Addiction Biology. 15: 185-199.
Chen G, Reilly M, Kozell L, Hitzemann R, Buck KJ (2009). Chronic alcohol withdrawal severity is associated with neuronal activation of limbic and basal ganglia circuitry in mice. Alcohol 43:411-20.
Kozell LB, Walter NAR, Milner LC, Wickman K, Buck KJ (2009). Mapping a barbiturate withdrawal locus to a 0.44Mb interval and analysis of a novel null mutant identifies a role for Kcnj9 (GIRK3) in withdrawal from pentobarbital, zolpidem, and ethanol. Journal of Neuroscience. 29:11662-11673.
- B.S. (1984) University of Minnesota
- Ph.D. (1990) Colorado Health Sciences Center
- Postdoctoral fellow (1990-91) Colorado Health Sciences Center (with Dr. James Sikela)
- Postdoctoral fellow (1991-94) Vollum Institute (with Drs. Oliver Civelli and Susan Amara, Howard Hughes Investigator)
- 1995-2002. Assistant Professor, Medical Psychology/Behavioral Neuroscience, OHSU
- 2002-2008. Associate Professor, Behavioral Neuroscience, OHSU, Portland, OR
- 2002-present. VA Scientist, VAMC-Portland, OR
- 2008-present. Professor, Behavioral Neuroscience, OHSU, Portland, OR
Kayaking, biking, gardening, standup comedy, mysteries, soccer mom