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NMDA Receptor Activation Potentiates Inhibitory Transmission through GABA Receptor-Associated Protein-Dependent Exocytosis of GABA sub(A) Receptors
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 sub(A) receptors (GABA sub(A)Rs) are also subject to regulation and that GABA sub(A)R trafficking may con...
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Published in: | The Journal of neuroscience 2007-12, Vol.27 (52), p.14326-14337 |
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Main Authors: | , , , |
Format: | Article |
Language: | English |
Online Access: | Get full text |
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Summary: | 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 sub(A) receptors (GABA sub(A)Rs) are also subject to regulation and that GABA sub(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 sub(A)Rs at the dendritic surface of hippocampal neurons. This NMDA stimulus increases miniature IPSC amplitudes and requires the activity of Ca super(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 sub(A)Rs. In addition, they reveal that the bidirectional trafficking of AMPA and GABA sub(A) receptors can be driven by a single glutamatergic stimulus, providing a potent postsynaptic mechanism for modulating neuronal excitability. |
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ISSN: | 0270-6474 1529-2401 |