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William T. Greenough
Professor
A.B., University of Oregon-Eugene
Ph.D., University of California-Los Angeles (Psychology)
Brain plasticity in learning and memory; cellular signalling in brain plasticity; mechanisms
of brain development; role of experience in brain maturation
Our earlier work showed that, in animals reared in complex social and sensory environments,
neurons had more extensive dendritic fields and more synapses than in “normal” cage-reared
animals. Similar results were found with adult rats, suggesting that new synapses underlie
memory. More recently, we have found that various forms of adult learning also increase synapse
numbers. Similar or greater amounts of activity that do not involve learning do not substantially
affect numbers of synapses, although extensive physical activity does alter brain vasculature. We
recently discovered that proteins are synthesized at synapses in response to neurotransmitter
activation of postsynaptic receptors; we have worked out many details of a novel signalling
pathway that leads from glutamate receptor activation to protein synthesis. Recently, several
findings have drawn our attention to basic research approaches to human medical problems. We
have discovered that a number of proteins, including FMRP, the protein that is missing in fragile
X mental retardation syndrome, are synthesized at the synapse under the control of this pathway.
To further specify the relationship between synaptic change and brain function, we are (1)
studying the roles of various cellular signalling and regulatory mechanisms in learning and
memory; (2) examining the mechanisms coordinating neural, glial, and vascular responses to the
demands of experience; (3) examining the effects of learning upon the morphology of cerebellar
neurons and their synapses; and (4) pursuing the detailed circuitry involved in motor learning,
using electrophysiological assessment in vivo and in vitro, immunocytochemistry, in situ
hybridization, optical and electron microscopy, and computer-based analytic and reconstruction
techniques.
Other research areas: Quantitative stereology; roles of sensory experience, hormones,
and neurotrophic and neuromodulatory substances in mammalian brain development.
Selected Publications
If only 6 are allowed, do those with *’s
*Irwin, S.A., Patel, B., Idupulapati, M., Harris, J.B., Cristostomo, R., Larsen, B.P., Kooy, F.,
Willems, P.J., Cras, P., Kozlowski, P.B., Swain, R.A., Weiler, I.J., and Greenough, W.T.
Abnormal dendritic spine characteristics in the temporal and visual cortices of patients with
Fragile-X Syndrome: A quantitative examination. American Journal of Medical Genetics,
98:161-167, 2001.
*Greenough, W.T., Klintsova, A.K., Irwin, S.A., Galvez, R., Bates, K.E., and Weiler, I.J.
Synaptic regulation of protein synthesis and the fragile X protein. PNAS, 98: 7101-7106, 2001.
*Irwin, S.A., Idupulapati, M., Gilbert, M.E., Harris, J.B., Chakravarti, A., Rogers, E.J.,
Crisostomo, R.A., Larsen, B.P., Mehta, A.B., Alcantara, C.J., Patel, B., Swain, R.A., Weiler, I.J.,
Oostra, B. A., and Greenough, W.T. Dendritic spine and dendritic field characteristics of layer V
pyramidal neurons in the visual cortex of fragile-x knockout mice. American Journal of Medical
Genetics, 111:140-146, 2002.
*Angenstein, F., Evans, A.M., Settlage, R.E., Moran, S.T., Ling, S-C., Klintsova, A.Y.,
Shabanowitz, J., Hunt, D.F. and Greenough, W.T. A receptor or activated C kinase (RACK1) is
part of mRNP-complexes associated with polyA-mRNAs in neurons. Journal of Neuroscience,
22:8827-8837, 2002.
*Federmeier, K. D.,Kleim, J. A., and Greenough, W. T. Multiple synapse formation in the
cerebellar cortex after complex motor learning. Neuroscience Letters, 332:180-184, 2002.
Grossman, A.W., Churchill, J.D., McKinney, B.C., Kodish, I.M., Otte, S.L. and Greenough, W.T.
Experience effects on brain development: Possible contributions to psychopathology. Journal of
Child Psychology and Psychiatry, 41:33-63, 2003.
*Miyashiro, K., Beckel-Mitchener, Purk, T.P., Kelly, A., Becker, K., Barret, T. Weiler, I.J.,
Greenough, W.T. and Eberwine. J. RNA cargoes associated with the fragile X mental retardation
protein reveal deficits in cellular functioning in FMR1 null mice. Neuron, 37: 417-431, 2003.
Swain, R.A., Harris, A.B., Wiener, E.C., Dutka, M.V., Morris, H.D., Theien, B.E., Konda, S.,
Engberg, K., Lauterbur, P.C. and Greenough, W.T. Prolonged exercise induces angiogenesis and
increases cerebral blood volume in primary motor cortex of the rat. Neuroscience, 117:10371046, 2003.