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Increased O‐GlcNAcylation Induces Synaptic Depression and Prevents LTP at Hippocampal CA3‐CA1 Synapses
Author(s) -
Taylor Erica,
Wang Kai,
Marchase Richard B.,
Chatham John C.,
McMahon Lori L.
Publication year - 2011
Publication title -
the faseb journal
Language(s) - English
Resource type - Journals
SCImago Journal Rank - 1.709
H-Index - 277
eISSN - 1530-6860
pISSN - 0892-6638
DOI - 10.1096/fasebj.25.1_supplement.855.4
Modification of serine/threonine residues of nucleocytoplasmic proteins by O‐linked‐N‐acetylglucosamine (O‐GlcNAc) plays a central role in regulating diverse cellular functions. In brain, hippocampal neurons express high levels of O‐GlcNAc transferase and O‐GlcNAcase which catalyze the addition and removal of O‐GlcNAc from proteins. Given the critical role of the hippocampus in learning and memory, surprisingly little is known regarding how O‐GlcNAcylation modulates synaptic strength and long‐term plasticity, a cellular correlate of learning and memory. The goal of this study was to determine the impact of increased O‐GlcNAc on basal glutamatergic transmission and NMDAR dependent long‐term potentiation (LTP) and depression (LTD). We performed extracellular dendritic field potential recordings from CA3‐CA1 synapses in rat hippocampal slices. Acutely increasing O‐GlcNAc, by increasing synthesis with exogenous glucosamine (100μM) or inhibiting O‐GlcNAcase with PUGNAc (30μM), elicits significant synaptic depression (15 ±.036% p<0.05) that lasts at least 1 hr. Western blot analysis confirmed a significant increase in protein O‐GlcNAcylation. Increased O‐GlcNAc prevented stable expression of LTP, while it had no effect on the magnitude of LTD. These results demonstrate for the first time that protein O‐GlcNAcylation contributes to the acute regulation of synaptic transmission and plasticity. Supported by: NINDS NS063359 & NIDDK 5 F31 DK084798 ‐02