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Regulation of hippocampal long‐term potentiation and long‐term depression by diacylglycerol kinaseζ
Author(s) -
Seo Jinsoo,
Kim Karam,
Jang Seil,
Han Seungnam,
Choi SeYoung,
Kim Eunjoon
Publication year - 2012
Publication title -
hippocampus
Language(s) - English
Resource type - Journals
SCImago Journal Rank - 1.767
H-Index - 155
eISSN - 1098-1063
pISSN - 1050-9631
DOI - 10.1002/hipo.20889
Subject(s) - long term potentiation , long term depression , metabotropic glutamate receptor , diacylglycerol kinase , chemistry , neuroscience , synaptic plasticity , nmda receptor , schaffer collateral , metabotropic receptor , glutamate receptor , hippocampus , microbiology and biotechnology , receptor , ampa receptor , biology , kinase , protein kinase c , biochemistry
Diacylglycerol (DAG) is an important signaling molecule at neuronal synapses. Generation of synaptic DAG is triggered by the activation of diverse surface receptors including N ‐methyl‐ D ‐aspartate (NMDA) receptors and metabotropic glutamate receptors. The action of DAG is terminated by enzymatic conversion of DAG to phosphatidic acid (PA) by DAG kinases (DGKs). DGKζ, one of many mammalian DGKs, is localized to synapses through direct interaction with the postsynaptic scaffolding protein PSD‐95, and regulates dendritic spine maintenance by promoting DAG‐to‐PA conversion. However, a role for DGKζ in the regulation of synaptic plasticity has not been explored. We report here that Schaffer collateral‐CA1 pyramidal synapses in the hippocampus of DGKζ‐knockout (DGKζ −/− ) mice show enhanced long‐term potentiation (LTP) and attenuated long‐term depression (LTD). The attenuated LTD at DGKζ −/− synapses involves both NMDA receptors and metabotropic glutamate receptors. These changes in LTP and LTD were reversed by phospholipase C inhibition, which blocks DAG production. Similar reversals in both LTP and LTD were also induced by inhibition of protein kinase C, which acts downstream of DAG. These results suggest that DGKζ regulates hippocampal LTP and LTD by promoting DAG‐to‐PA conversion, and establish that phospholipase C and protein kinase C lie upstream and downstream, respectively, of DGKζ‐dependent regulation of hippocampal LTP and LTD. © 2010 Wiley Periodicals, Inc.