Models of Synaptic Plasticity: Potential Roles in Development, Cognition, and Disease
March 13, 2008 8 AM to 5 PM Alumni House, VCU
Download a pdf with all speaker info here
Dan Madison, PhD
Plasticity During Different Synaptic States
Associate Professor of Molecular and Cellular
Physiology
Stanford University School of Medicine
http://med.stanford.edu/profiles/Vernon_Madison/
http://www.stanford.edu/~madison/madlab/
Talk
Summary:
Synaptic
States: Our published data, showed
that activity dependent synaptic plasticity exhibits a mechanistic
state-dependence. When undergoing
LTP, LTD, depotentiation, silence synapse awakening, and similar plasticity, the
synaptic strength changes occur by the common final path of the regulation of
AMPA receptor concentration in the postsynaptic membrane.
But the mechanisms by which these receptors are trafficked into and out
of the membrane change, depending on what plasticity the synapse has undergone.
So far, we have defined 7 and possibly 8 distinct mechanistic plasticity
states of the synapse. As an example
of what I mean by 'states', the
strength of a naive active synapse can be suppressed by low-frequency synaptic
activity via activation of the NMDA receptor.
But if you first potentiate the synapse,
the same low-frequency activity still depresses it's strength, but now
through the activation of an mGluR receptor (and the NMDAR sensitivity is
removed). So naive-active synapses
and potentiated synapses can both undergo similar plasticity, but the underlying
mechanisms are different. In a
similar vein, naive-active synapses and silent synapses can both be potentiated
by high-frequency activity that adds AMPARs to the postsynaptic mechanism, but
these AMPARs come from different sources and are regulated by different
underlying mechanisms. In our
more recent unpublished data, we have found that a major factor underlying these
states is the insertion or removal of AMPARs having different subunit
composition. The main thrust of the
talk is to use the rules that states provide to understand the mechanisms
underlying synaptic plasticity. By
doing this, we have just recently completed a fairly comprehensive model to
explain how the trafficking of AMPARs with different subunit compositions
underlies much of the state-dependence of plasticity.
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R. Douglas Fields,
PhD
"Synaptic Plasticity: Venturing Beyond the
Cleft"
Chief,
Nervous System Development and Plasticity Section
National
Institutes Health, NICHD
http://nsdps.nichd.nih.gov/research.html
Talk
Summary:
The once hotly debated issue of the relative
importance of the presynaptic versus postsynaptic membrane in regulating
synaptic plasticity fueled years of productive research, but now the field is
venturing beyond the synaptic cleft.
Signaling to the nucleus and cell-cell interactions of many types are
important in regulating synaptic strength.
Hebb's postulate that the coincident firing of neurons is the essential
trigger for learning implies the importance of action potentials, not simply
synaptic potentials, in regulating plasticity.
Different intracellular signaling pathways are activated by action
potentials and synaptic potentials, and our research suggests that gene
transcription necessary for consolidating early into late-phase LTP does not
require synaptic signaling to the nucleus, but rather somatic action potentials.
Cell-cell interactions with non-neuronal cells, astrocytes, also regulate
plasticity of synapses, but less-well appreciated is the transmission of
impulses through axons, which is regulated in part by myelinating glia.
The conduction velocity and synchrony of impulses are critical in
information processing and synaptic transmission.
New research suggests that myelinating glia sense impulse activity in
axons and regulate the process of myelination.
This new aspect of plasticity encompasses white matter changes in
addition to the grey matter changes in learning, and the molecular mechanisms
for activity-dependent communication between axons and myelinating glia are
being identified.
The activity-dependent communication involves extracellular ATP and
cytokines, which are relatively less well-explored in LTP research.
Our research finds impaired LTP in mice lacking the gene for the cytokine
LIF, and cell-cell interactions mediated by LIF and ATP are important in
activity-dependent regulation of nervous system development and myelination.
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Alfredo
Kirkwood, PhD
"Neuromodulation
of Synaptic Plasticity"
Associate
Professor
Zanvyl
Krieger Mind/Brain Institute
Johns Hopkins University
http://neuroscience.jhu.edu/AlfredoKirkwood.php
Talk
Summary:
Sensory experience can shape the connectivity of the cerebral cortex during its
maturation in infants, and also during learning in adults. These neural
modifications depend critically on neuromodulators conveying information of the
behavioral state of the organism such that passive experience does not leave
permanent traces on cortical connectivity. Research on the mechanisms of neural
plasticity indicated that the connection between two neurons can be either
strengthened or weakened depending on their patterns of neural activity,
particularly on their "timing" relationships. Typically, synapses
become either stronger or weaker depending on whether pre- or postsynaptic
activity occurs first.
I will discuss evidence indicating that the "timing-dependence"
rules of synaptic modification are not fixed, but emerge from the interactions
of neuromodulators. As one important consequence, a given pattern of pre- and
postsynaptic activity can modify synapses in opposite directions depending on
the neuromodulators present.
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Eric
Klann, PhD
"Altered
Synaptic Plasticity and Behavior in Mouse Models of Mental Retardation"
Professor
of Neuroscience
Center for Neuroscience
New York University
http://www.cns.nyu.edu/corefaculty/Klann.php
Talk
Summary:
Genetic deletion and/or mutations of several
translation repressor proteins, including fragile X mental retardation protein (FMRP)
and tuberous sclerosis complex 1 and 2 (TSC1/2), are associated with human
mental retardation. Because de novo protein synthesis is one of the hallmarks of
long-lasting synaptic plasticity and long-term memory, genetically engineered
mouse models that lack translational control proteins have the potential to
provide insight into the molecular and cellular basis of mental retardation and
autism. In this presentation, synaptic plasticity and behavioral studies of mice
that lack specific translation factors and translation regulatory proteins,
including FMRP, will be discussed. These studies have revealed interesting links
between the biochemical activities of translation factors, synaptic plasticity,
and behavior.
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Per
Svenningsson, MD, PhD
"Involvement
of 5-HT1B Receptors and p11 in Depression and Parkinson's Disease"
Group
Leader
Department of Physiology and Pharmacology
Karolinska Institute, Stockholm
http://ki.se/ki/jsp/polopoly.jsp?d=9791&l=en
Talk
Summary:
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Christina
Vargas-Irwin, PhD
"Individual
Differences in Addictive Behavior: A Process Approach"
Research
Associate Professor
Department of Pharmacy
Virginia Commonwealth University
http://www.pharmacy.vcu.edu/pharmacy/facdetail.aspx?id=784
Talk
Summary:
The progression towards addictive behavior has
been described as involving the transition through several stages, beginning
with the initial contact with the drug, followed by its regular use, which, in
turn may finally result in substance dependence, or addiction. This sequence is
not deterministic, since in humans, most drug users don't become drug dependent,
and many factors, such as availability, genetics, history of drug use, stress,
and life events contribute to the final outcome. Research in this area has
traditionally approached individual differences in addictive behavior from a
static trait centered perspective, which is inherently silent about behavioral
dynamics and non-specific about gene-environment interactions.
We pursue here a process-entered approach to the study of addictive
behavior, focused on the reward and hedonic properties of drugs. From this
perspective, individual differences are conceived not as static traits, but
rather as dynamic parametric differences in common behavioral processes. This
approach is illustrated with examples from our own research
and its implications to the links between addictive behavior and synaptic
plasticity are highlighted.
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