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

• Published in: The Journal of neuroscience Vol. 27; no. 52; pp. 14326 - 14337
• Main Authors: Marsden, Kurt C, Beattie, Jennifer B, Friedenthal, Jenna, Carroll, Reed C
• Format: Journal Article
• Language: English
• Published: Soc Neuroscience 26.12.2007; Society for Neuroscience
• ISSN: 0270-6474; 1529-2401
• DOI: 10.1523/JNEUROSCI.4433-07.2007

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.