2010 Fiscal Year Final Research Report
Acetylcholine mediates learning-dependent AMPA receptor delivery into the CA3-CA1 synapses
| Project/Area Number |
20590232
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| Research Category |
Grant-in-Aid for Scientific Research (C)
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| Allocation Type | Single-year Grants |
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| Section | 一般 |
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| Research Field |
Environmental physiology (including Physical medicine and Nutritional physiology)
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| Research Institution | Yokohama City University |
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Principal Investigator |
MITSUSHIMA Dai Yokohama City University, 医学部, 准教授 (70264603)
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| Project Period (FY) |
2008 – 2010
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| Keywords | 海馬 / アセチルコリン / 学習・記憶 / AMPA受容体 / シナプス移行 |
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| Research Abstract |
By combining in vivo gene delivery with in vitro patch-clamp recordings, we found that hippocampal-dependent inhibitory avoidance (IA) learning drives recombinant GluR1, an AMPA receptor subunit, into synapses formed between CA3 and CA1 pyramidal neurons. Bilateral expression of delivery blocker further revealed that contextual learning requires AMPA receptor delivery in CA1 synapses. Pretreatment of scopolamine, not only impaired the IA learning, but also blocked the AMPA receptor delivery. In paired-recording study, scopolamine pretreatment successfully blocked the effect of mutated fragment of GluR1 cytoplasmic tail (GFP-MPR-DD), a construct inhibits learning-dependent synaptic delivery of AMPA receptors. Conversely, expression of control fragment (GFP-MPR-AA) did not affect the learning-dependent delivery. Further, extracellular acetylcholine level at CA1 region significantly increased during and after IA learning for 60 min. Control animals (such as naive, shock only, or walk through rats) did not show the increase. These results suggest that cholinergic activation is required for learning-dependent AMPA receptor delivery into the CA3-CA1 synapses.
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