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- Title
O-GlcNAcylation of AMPA Receptor GluA2 Is Associated with a Novel Form of Long-Term Depression at Hippocampal Synapses.
- Authors
Taylor, Erica W.; Wang, Kai; Nelson, Amy R.; Bredemann, Teruko M.; Fraser, Kyle B.; Clinton, Sarah M.; Puckett, Rosemary; Marchase, Richard B.; Chatham, John C.; McMahon, Lori L.
- Abstract
Serine phosphorylation of AMPA receptor ( AMPAR) subunits GluA 1 and GluA2 modulates AMPAR trafficking during long-term changes in strength of hippocampal excitatory transmission required for normal learning and memory. The post-translational addition and removal of O-linked β-N-acetylglucosamine (O-GlcNAc) also occurs on serine residues. This, together with the high expression of the enzymes O-GlcNAc transferase (OGT) and β-N-acetylglucosamindase (O-GlcNAcase), suggests a potential role for O-GlcNAcylation in modifying synaptic efficacy and cognition. Furthermore, because key synaptic proteins are O-GlcNAcylated, this modification may be as important to brain function as phosphorylation, yet its physiological significance remains unknown. We report that acutely increasing O-GlcNAcylation in Sprague Dawley rat hippocampal slices induces an NMDA receptor and protein kinase C-independent long-term depression (LTD) at hippocampal CA3-CA1 synapses (O-GcNAc LTD). This LTD requires AMPAR GluA2 subunits, which we demon-strate are O-GlcNAcylated. Increasing O-GlcNAcylation interferes with long-term potentiation, and in hippocampal behavioral assays, it prevents novel object recognition and placement without affecting contextual fear conditioning. Our findings provide evidence that O-GlcNAcylation dynamically modulates hippocampal synaptic function and learning and memory, and suggest that altered O-GlcNAc levels could underlie cognitive dysfunction in neurological diseases.
- Subjects
AMPA receptors; MENTAL depression; HIPPOCAMPUS (Brain); SYNAPSES; PHOSPHORYLATION; N-acetylglucosamine
- Publication
Journal of Neuroscience, 2014, Vol 34, Issue 1, p10
- ISSN
0270-6474
- Publication type
Article
- DOI
10.1523/JNEUROSCI.4761-12.2014