The regulation of the AMPA subtype of the glutamate receptor is believed to contribute to long term changes in synaptic strength; changes believed to be important for many forms of experience-dependent plasticity. The surface expression of AMPA receptors (AMPARs) appears to be tightly regulated despite their constant cycling. In addition AMPAR surface expression has been shown to rapidly increase or decrease in response to stimulation. The detailed molecular mechanisms underlying AMPAR receptor trafficking, however, remain elusive. In this proposal, I outline a series of experiments that will investigate how the inflammatory cytokine tumor necrosis factor-alpha (TNFalpha), which has been shown to alter excitatory synaptic transmission, impacts AMPAR trafficking. Preliminary data suggests that TNFalpha induces a robust and rapid increase in the surface expression of AMPARs in cultured neurons. I will confirm this observation and examine if this increase is occurring at synaptic sites. I will then test whether TNFalpha has an endogenous role in maintaining AMPAR surface expression and begin to determine the molecular signaling pathways involved. These data should significantly enhance our knowledge of AMPAR trafficking and the influence of TNFalpha on synaptic function.

Agency
National Institute of Health (NIH)
Institute
National Institute of Mental Health (NIMH)
Type
Postdoctoral Individual National Research Service Award (F32)
Project #
5F32MH065752-02
Application #
6626134
Study Section
Special Emphasis Panel (ZRG1-F03A (20))
Program Officer
Desmond, Nancy L
Project Start
2002-05-01
Project End
Budget Start
2003-05-01
Budget End
2004-04-30
Support Year
2
Fiscal Year
2003
Total Cost
$48,148
Indirect Cost
Name
Stanford University
Department
Psychiatry
Type
Schools of Medicine
DUNS #
009214214
City
Stanford
State
CA
Country
United States
Zip Code
94305
Bjartmar, Lisa; Huberman, Andrew D; Ullian, Erik M et al. (2006) Neuronal pentraxins mediate synaptic refinement in the developing visual system. J Neurosci 26:6269-81
Stellwagen, David; Beattie, Eric C; Seo, Jae Y et al. (2005) Differential regulation of AMPA receptor and GABA receptor trafficking by tumor necrosis factor-alpha. J Neurosci 25:3219-28