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NMDA Receptor Activation Potentiates Inhibitory Transmission through GABA Receptor-Associated Protein-Dependent Exocytosis of GABA A Receptors

2007; Society for Neuroscience; Volume: 27; Issue: 52 Linguagem: Inglês

10.1523/jneurosci.4433-07.2007

1529-2401

Kurt C. Marsden, Jennifer B. Beattie, Jenna Friedenthal, Reed C. Carroll,

Lipid Membrane Structure and Behavior

The trafficking of postsynaptic AMPA receptors (AMPARs) is a powerful mechanism for regulating the strength of excitatory synapses. It has become clear that the surface levels of inhibitory GABA A receptors (GABA A Rs) are also subject to regulation and that GABA A R trafficking may contribute to inhibitory plasticity, although the underlying mechanisms are not fully understood. Here, we report that NMDA receptor activation, which has been shown to drive excitatory long-term depression through AMPAR endocytosis, simultaneously increases expression of GABA A Rs at the dendritic surface of hippocampal neurons. This NMDA stimulus increases miniature IPSC amplitudes and requires the activity of Ca 2+ calmodulin-dependent kinase II and the trafficking proteins N -ethylmaleimide-sensitive factor, GABA receptor-associated protein (GABARAP), and glutamate receptor interacting protein (GRIP). These data demonstrate for the first time that endogenous GABARAP and GRIP contribute to the regulated trafficking of GABA A Rs. In addition, they reveal that the bidirectional trafficking of AMPA and GABA A receptors can be driven by a single glutamatergic stimulus, providing a potent postsynaptic mechanism for modulating neuronal excitability.