Differential Regulation of AMPA Receptor and GABA Receptor Trafficking by Tumor Necrosis Factor-α

• DOI: 10.1523/jneurosci.4486-04.2005
• Publication Date: 2005-03-23T23:30:54Z
• Authors: David Stellwagen; Eric C. Beattie; Jae Y. Seo; Robert C. Malenka
• Keywords: Long-term depression; Silent synapse; SGK1

The proinflammatory cytokine tumor necrosis factor-α (TNFα) causes a rapid exocytosis of AMPA receptors in hippocampal pyramidal cells and is constitutively required for the maintenance normal surface expression receptors. Here we demonstrate that TNFα acts on neuronal TNFR1 to preferentially exocytose glutamate receptor 2-lacking through phosphatidylinositol 3 kinase-dependent process. This increases excitatory synaptic strength while changing molecular stoichiometry Conversely, an endocytosis GABA A receptors, resulting fewer decrease inhibitory strength. These results suggest can regulate circuit homeostasis manner may exacerbate excitotoxic damage from insults.