Gary Westbrook, M.D.
Senior Scientist and Co-Director, Vollum Institute
Rocky and Julie Dixon Professor of Neurology
Director, Neuroscience Graduate Program
Lab Phone: 503-494-5436
Office: Vollum, 2431A
Dr. Westbrook received his medical training and did graduate study in Biomedical Engineering at Case Western Reserve University. He was then an intern and resident at Mt. Auburn Hospital in Boston (Internal Medicine) and at the Washington University School of Medicine in St. Louis (Neurology). After clinical training, he spent six years in basic neuroscience research at the National Institutes of Health before moving to the Vollum Institute in 1987. He is a senior scientist and co-director at the Vollum Institute and professor of neurology in the School of Medicine. Dr. Westbrook has been active in the development of the Jungers Center, a joint effort between the Vollum Institute and the Department of Neurology, as well as in OHSU training activities in disease-oriented neuroscience research. He initiated the Neurobiology of Disease course in the graduate program, and currently serves as the director of the Neuroscience Graduate Program at OHSU. Dr. Westbrook has been the recipient of several research prizes, including a Jacob Javits Award and a Merit Award from the National Institutes of Health. He is a past editor-in-chief of the Journal of Neuroscience. He has served as a member of the Advisory Council of the National Institute of Neurological Diseases and Stroke (NINDS) and the NIH Council of Councils, which oversees the Common Fund.
Summary of Current Research
(For a video summary of the Westbrook lab, see www.ohsu.edu/vollum and click on “A walk through a Vollum lab”)
Synapses move information around the nervous system, and their dysfunction has been increasingly recognized as a factor in a wide range of neurodevelopmental disorders and neuropsychiatric diseases. The goal of the Westbrook lab is to understand normal and abnormal synaptic transmission in the central nervous system. We use electrical and optical recording as well as molecular methods to examine the formation, function, and plasticity of excitatory and inhibitory synapses. These synapses mediate the majority of rapid information transfer in the brain. Our experiments are directed at several levels, from regulation and localization of individual receptors to the behavior of single synapses, and to the mechanisms by which small networks of synapses regulate learning and memory and sensory processing. Our earlier work was mostly directed at the level of receptors, particularly N-methyl-D-aspartate receptors, and the function of single synapses. Our work has now largely shifted to studies of small networks or microcircuits in the hippocampus and olfactory system. Our goal is to understand how such circuits are formed, regulate their activity and contribute to the function of neural systems.
Most of the current work in our lab focuses on two projects. In the hippocampus, we are examining the incorporation of newborn neurons into the synaptic network of the hippocampus. We started this work using a unique transgenic mouse in which newborn dentate granule cells are marked with enhanced green fluorescent protein (EGFP) under control of the proopiomelanocortin promoter. Our results suggest that development of dendrites and formation of synapses is delayed due to the local environment of the adult hippocampus. We are using these and other mice to examine the functional and morphological development of new synapses, as well as the molecules that control dendritic development. We are using candidate gene approaches, unbiased genetic screens, as well as network perturbations to identify molecules that are critical to circuit formation. In order to study candidate genes, we use viral-mediated gene transfer in vivo, then assess the physiological behavior of synapses using imaging and electrophysiological recording in acute brain slices. We are also examining how the incorporation of newborn neurons is affected by seizures and brain injury. The integration of these newborn neurons provides a unique window into the formidable barriers to synaptogenesis, dendritic outgrowth and circuit formation in the adult nervous system. In terms of the potential for stem cells and cell replacement approaches, these barriers are perhaps more daunting than even cell differentiation and survival.
In the other project, we are using the olfactory system to examine the role of microcircuits in the function of this sensory system. We are interested in understanding how the unique synaptic architecture of the bulb shapes the highly organized incoming sensory information, i.e. what aspects of the circuit control detection and discrimination of odors. Our current experiments focus on a set of 1000 neuropil structures in the olfactory bulb called glomeruli. Neurons within a glomerulus receive specific sensory input and show highly synchronized activity. Our experiments have revealed both slow and fast coordination of activity in glomeruli involving slow modulatory receptors such as metabotropic glutamate receptor 1, as well as rapid action potential synchronization involving the gap junction molecule, connexin 36, on distal dendrites. We are currently examining control of this circuit by periglomerular neurons that release both dopamine and GABA. We are using amperometry to measure quantal release of dopamine and optogenetics to activate these cells in the olfactory bulb circuitry.
Magill ST, Cambronne XA, Luikart BW, Lioy DT, Leighton BH, Westbrook GL, Mandel G, Goodman RH. (2010) microRNA-132 regulates dendritic growth and arborization of newborn neurons in the adult hippocampus. Proc Natl Acad Sci 107: 20382-20387. PMID: 21059906; PMCID: PMC2996687.
Luikart BW, Schnell E, Washburn EK, Bensen AL, Tovar KR, Westbrook GL. (2011) Pten knockdown in vivo increases excitatory drive onto dentate granule cells. J Neurosci 31: 4345-4354. PMID: 21411674.
McGinley MJ, Westbrook GL. (2011) Membrane and synaptic properties of pyramidal neurons in the anterior olfactory nucleus. J Neurophysiol 105:1444-1453. PMID: 21123663.
Luikart BW, Bensen AL, Washburn EK, Perederiy JV, Su KG, Li Y, Kernie SG, Parada LF, Westbrook GL. (2011) miR-132 mediates the integration of newborn neurons into the adult dentate gyrus. PLoS One 6: e19077. PMID: 21611182; PMCID: PMC3096628.
Borisovska M, McGinley MJ, Bensen A, Westbrook GL. (2011) Loss of olfactory cell adhesion molecule reduces the synchrony of mitral cell activity in olfactory glomeruli. J Physiol 589:1927-1941. PMID: 21486802.
Luikart BW, Perederiy JV, Westbrook GL. (2012) Dentate gyrus neurogenesis, integration and microRNAs. Behav Brain Res 227:348-355. PMID: 21443907.
Westbrook GL (2012) Seizures and Epilepsy. In Principles of Neural Science, 5th Edition (Kandel, Schwartz Jessell, Siegelbaum, Hudspeth, eds.).