Molecular
Mechanisms of Memory Acquisition
My
lab focuses on signaling
pathways
that are triggered by activation
of NMDA receptors following
vesicular release of glutamate
from synaptic terminals.
Activation of these receptors is
critical for long-term changes in
synaptic strength, which is
believed to be one of many neural
mechanisms that contribute to
learning and memory in animals.
Many of these signaling pathways
(an example would be Ras/ERK
activation) can regulate
trafficking of AMPA receptors (AMPARs)
to and from the synapse. Because AMPAR
trafficking underlies certain
forms of long-term synaptic
plasticity,
understanding the signaling
pathways that regulate this
trafficking will likely uncover
mechanisms utilized during
acquisition, consolidation and
retrieval of memories. In
addition, emerging evidence from
several lines of research suggests
that many common neurological
disorders including Alzheimer’s,
schizophrenia and familial mental
retardation are associated with
synaptic dysfunction. Therefore,
understanding signaling mechanisms
that subserve synaptic plasticity
and learning may help unravel the
pathophysiology of common brain
afflictions.
Presently,
much of the lab’s focus is
devoted to understanding how
SynGAP, a neuron-specific RasGAP, functions
to regulate signaling pathways
downstream of NMDA receptor
activation. SynGAP protein is a
major constituent of the
postsynaptic density, binds to
NMDA receptors, is phoshorylated
by CamKII (in response NMDA
receptor activation) and can
convert GTPases to an “off”
state resulting in inhibition of
certain postsynaptic signaling
cascades. This has lead to the lab
hypothesis that SynGAP, through
its GTPase activating domain
(GAP), rapidly alters signaling
pathways at synapses and this in
turn regulates neuronal
plasticity.
Indeed, my lab has shown
that SynGAP can regulate
postsynaptic signaling cascades (ERK
and P38 MAPK), synaptic strength
and AMPAR trafficking. Further,
SynGAP mutant mice perform poorly
on spatial memory tests,
suggesting that this protein is
involved in signaling pathways
that subserve learning and memory.
Click
here for ongoing lab projects
Gavin Rumbaugh (b. 1974) received his Ph.D. in Biophysics and Pharmacology from
Georgetown University in 2000. He received postdoctoral training at The Johns Hopkins University School of Medicine where he worked with Richard L. Huganir, PhD. He is now an Assistant Professor of Neurobiology.
