Office: VBR 335
Lab: (509) 335-6851
Phone: (509) 335-8211
Normal cognitive processing, i.e. learning and memory consolidation,
requires physical remodeling of synaptic connections. This remodeling
commonly manifests as changes in dendritic arborization and alterations
in the size, shape and density of dendritic spines. Since spines
represent the site for excitatory synaptic inputs, modification of spine
properties translates into changes in the efficacy of synaptic
communication. Not surprisingly, abnormalities in dendritic
arborization and spinogenesis, which diminish neuronal connectivity, are
a common feature of the cognitively compromised aging brain as well as
numerous forms of mental retardation including Fragile X, Fetal alcohol,
Downs and Rett syndromes.
It is clear that changes in synaptic activity and neurotrophic
factors (e.g., BDNF) are effective initiators of the remodeling process
and result in long-term alterations in dendrite and spine structure.
What is not known are the molecular mechanisms that underlie how they
stimulate dendritic spine formation.
The primary focus of my labs research is to determine the molecular and
cellular mechanism by which synaptic activity and neurotrophic factors
influence neuronal development. Our lab and others have demonstrate that
synaptic activity and BDNF increase both intracellular calcium and the
transcription of a subset of CREB-dependent genes, both of which are
required to promote rearrangement of the cytoskeleton and formation of
dendritic spines. We use a multidisciplinary approach combining
disruption of key signaling cascades using dominant negative and
constitutively active mutants, genetic manipulations and pharmacology
with live imaging and confocal microscopy as well as both molecular and
biochemical techniques to evaluate the roles of different CREB regulated
gene products in regulating neuronal structural plasticity. As an
outcome of our research we hope to determine the key CREB controlled
genes activated by synaptic activity and BDNF, which regulate of
neuronal morphogenesis, and to determine how they shape the development
and modification of dendritic spines. In understanding the molecular
players involved in these processes, one may in the future be able to
develop therapies to treat neuronal developmental and/or psychiatric
disorders. Thus our studies have strong implications for underlying
causes of mental diseases.
Gary A. Wayman received his B.S. in Biochemistry from Washington
State University in 1988 and earned a Ph.D. in Pharmacology from the
University of Washington in 1995. He then went on to postdoctoral
training at the Vollum Institute, Oregon Health and Sciences University
(OHSU) from 1995-2001. In 2001 he was promoted to Research Assistant
Professor (Vollum Institute) and Assistant Professor (Department of Cell
and Developmental Biology) at OHSU. Dr. Wayman joined the Department of
IPN as an Assistant Professor in August 2007.
Davare MA, Fortin DA, Saneyoshi T, Nygaard S, Kaech S, Banker G,
Soderling TR, and Wayman GA
. TRPC5 channels activate
CaM-kinase IÎ³ to promote axon formation in hippocampal neurons. In
press J. Neuroscience.
Kim WY, Gonsiorek EA, Barnhart C, Davare MA, Engebose AJ, Lauridsen H,
Brunn D, Lesiak A, Wayman G,
Bucelli R, Higgins D, Lein
PJ. Statins decrease dendritic arborization in rat sympathetic neurons
by blocking RhoA activation. J. Neurochem, 2009, 108(4): 1057-71.
Yang D, Kim KH, Phimister A, Bachstetter AD, Ward TR, Stackman RW,
Mervis RF, Wisniewski AB, Klein SL, Kodavanti PR, Anderson KA,
Pessah IN, Lein PJ. Developmental exposure to
polychlorinated biphenyls interferes with experience-dependent dendritic
plasticity and ryanodine receptor expression in weanling rats. Environ
Health Perspect. 2009 Mar;117(3):426-35. Epub 2008 Sep 12.
Luikart BW, Zhang W, Wayman GA
, Kwon CH, Westbrook GL,
Parada LF. Neurotropin-dependent dendritic filopodial motility: a
convergence on PI3K signaling. J Neurosci. 2008 28(27): 7006-12.
, Davare M, Ando H, Fortin D, Varlamova O,
Cheng HY, Marks D, Obrietan K, Soderling TR, Goodman RH, Impey S. An
activity-regulated microRNA controls dendritic plasticity by
down-regulating p250GAP. Proc Natl Acad Sci U S A. 2008 Jul
1;105(26):9093-8. Epub 2008 Jun 24.
, Lee YS, Tokumitsu H, Silva A, Soderling TR.
Calmodulin-kinases: modulators of neuronal development and plasticity.
Neuron 2008 59(6): 914-31. Review.
Saneyoshi T, Wayman G
, Fortin D, Davare M, Hoshi N,
Nozaki N, Natsume T, Soderling TR. Activity-Dependent Synaptogenesis:
Regulation by a CaM-kinase kinase/CaM-kinase I/betaPIX signaling
complex. Neuron. 2008 Jan 10;57(1):94-107.
, Impey S, Marks D, Saneyoshi T, Grant WF,
Derkach V, Soderling TR. Activity-dependent dendritic arborization
mediated by CaM-kinase I activation and enhanced CREB-dependent
transcription of Wnt-2. Neuron. 2006 Jun 15;50(6):897-909.
Schmitt JM, Wayman GA
, Nozaki N, Soderling TR. Calcium
activation of ERK mediated by calmodulin kinase I. J Biol Chem. 2004 Jun
4;279(23):24064-72. Epub 2004 Mar 29.
*, Kaech S*, Grant WF, Davare M, Impey S,
Tokumitsu H, Nozaki N, Banker G, Soderling TR. Regulation of axonal
extension and growth cone motility by calmodulin-dependent protein
kinase I. J Neurosci. 2004 Apr 14;24(15):3786-94. (*contributed equally
to this work).
Soderling SH, Binns KL, Wayman GA
, Davee SM, Ong SH,
Pawson T, Scott JD. The WRP component of the WAVE-1 complex attenuates
Rac-mediated signalling. Nat Cell Biol. 2002 Dec;4(12):970-5.
Impey S, Fong AL, Wang Y, Cardinaux JR, Fass DM, Obrietan K,
, Storm DR, Soderling TR, Goodman RH. Phosphorylation
of CBP mediates transcriptional activation by neural activity and CaM
kinase IV. Neuron. 2002 Apr 11;34(2):235-44.
Walters MJ*, Wayman GA
,* Notis JC, Goodman RH,
Soderling TR, Christian JL. Calmodulin-dependent protein kinase IV
mediated antagonism of BMP signaling regulates lineage and survival of
hematopoietic progenitors. Development. 2002 Mar;129(6):1455-66.
(*contributed equally to this work.)
Walters MJ, Wayman GA
, Christian JL. Bone morphogenetic
protein function is required for terminal differentiation of the heart
but not for early expression of cardiac marker genes. Mech Dev. 2001
, Walters MJ, Kolibaba K, Soderling TR,
Christian JL. CaM kinase IV regulates lineage commitment and survival of
erythroid progenitors in a non-cell-autonomous manner. J Cell Biol. 2000
Impey S, Obrietan K, Wong ST, Poser S, Yano S, Wayman G
Deloulme JC, Chan G, Storm DR. Cross talk between ERK and PKA is
required for Ca2+ stimulation of CREB-dependent transcription and ERK
nuclear translocation. Neuron. 1998 Oct;21(4):869-83. PMID: 9808472 [PubMed
- indexed for MEDLINE]
Xia XM, Fakler B, Rivard A, Wayman G,
Keen JE, Ishii T, Hirschberg B, Bond CT, Lutsenko S, Maylie J, Adelman
JP. Mechanism of calcium gating in small-conductance calcium-activated
potassium channels. Nature. 1998 Oct 1;395(6701):503-7.
, Tokumitsu H, Soderling TR. Inhibitory
cross-talk by cAMP kinase on the calmodulin-dependent protein kinase
cascade. J Biol Chem. 1997 Jun 27;272(26):16073-6.
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