| Project/Area Number |
12680776
|
|---|
| Research Category |
Grant-in-Aid for Scientific Research (C)
|
| Allocation Type | Single-year Grants |
|---|
| Section | 一般 |
|---|
| Research Field |
Neuroscience in general
|
|---|
| Research Institution | OKAYAMA UNIVERSITY |
|---|
Principal Investigator |
MORIWAKI Akiyoshi Okayama University, Graduate School of Medicine and Dentistry, Associate Professor, 大学院・医歯学総合研究科, 助教授 (10144742)
|
|---|
| Co-Investigator(Kenkyū-buntansha) |
TOMIZAWA Kazuhito Okayama University, Graduate School of Medicine and Dentistry, Lecturer, 大学院・医歯学総合研究科, 講師 (40274287)
LI Sheng-tian Okayama University, Graduate School of Medicine and Dentistry, Assistant, 大学院・医歯学総合研究科, 助手 (90325093)
MATSUI Hideki Okayama University, Graduate School of Medicine and Dentistry, Professor, 大学院・医歯学総合研究科, 教授 (30157234)
MATSUSHITA Masayuki Okayama University, Graduate School of Medicine and Dentistry, Assistant, 大学院・医歯学総合研究科, 助手 (30273965)
|
|---|
| Project Period (FY) |
2000 – 2001
|
| Project Status |
Completed (Fiscal Year 2001)
|
| Budget Amount *help |
¥3,500,000 (Direct Cost: ¥3,500,000)
Fiscal Year 2001: ¥1,400,000 (Direct Cost: ¥1,400,000)
Fiscal Year 2000: ¥2,100,000 (Direct Cost: ¥2,100,000)
|
|---|
| Keywords | Long term potentiation / Late phase long-term potentiation / Nitric oxide / Ca^<2+> |
|---|
| Research Abstract |
A late phase long-term potentiation (L-LTP) that can be induced by three- or four-train tetanization, lasts more than 3 hr, and is reduced by inhibitors of protein kinase A or RNA synthesis. We examined contribution of nitric oxide(NO)signaling pathway in L-LTP at the Schaffer conateral-CA1 synapses in slices of mouse hippocampus. An inhibitor of NO synthase blocked L-LTP induced by three-train tetanization and reduced L-LTP induced by four-train tetanization, whereas an inhibitor of PKA was more effective in blocking four-train L-LTP than three-train L-LTP. Three-train L-LTP was also blocked by inhibitors of guanylyl cyclase or cGMP-dependent protein kinase (PKG). Conversely, either NO or cGMP analogs paired with one-train tetanization produced late-phase potentiation, and the cGMP-induced potentiation was blocked by inhibitors of protein or RNA synthesis and an inhibitor of PKG, but not by an inhibitor of PKA. To test a possible downstream target of PKG, we examined changes in phospho-CRE-binding protein (phospho-CREB) immunofluorescence in the CA1 cell body area and obtained results similar to those of foe electrophysiology experiments. These results suggest that NO contributes to L-LTP by stimulating guanylyl cyclase and cGMP dependent protein kinase, which acts in parallel with PKA to increase phosphorylation of foe transcription factor CREB.
|
