PI3Kγ is required for NMDA receptor-dependent long-term depression and behavioral flexibility

被引：125

作者：

Kim, Jae-Ick ^{[1
]}

Lee, Hye-Ryeon ^{[1
]}

Sim, Su-eon ^{[1
,2
]}

Baek, Jinhee ^{[1
]}

Yu, Nam-Kyung ^{[1
]}

Choi, Jun-Hyeok ^{[1
]}

Ko, Hyoung-Gon ^{[1
]}

Lee, Yong-Seok ^{[1
]}

Park, Soo-Won ^{[1
]}

Kwak, Chuljung ^{[1
]}

Ahn, Sung-Ji ^{[3
]}

Choi, So Yoen ^{[4
]}

Kim, Hyun ^{[4
]}

Kim, Kyoung-Han ^{[5
]}

Backx, Peter H. ^{[5
]}

Bradley, Clarrisa A. ^{[2
]}

Kim, Eunjoon ^{[6
]}

Jang, Deok-Jin ^{[7
]}

Lee, Kyungmin ^{[8
]}

Kim, Sang Jeong ^{[2
,3
]}

Zhuo, Min ^{[2
,5
]}

Collingridge, Graham L. ^{[2
,9
]}

Kaang, Bong-Kiun ^{[1
,2
]}

机构：

[1] Seoul Natl Univ, Coll Nat Sci, Natl Creat Res Initiat Ctr Memory, Dept Biol Sci, Seoul 151742, South Korea

[2] Seoul Natl Univ, Coll Nat Sci, Dept Brain & Cognit Sci, Seoul 151742, South Korea

[3] Seoul Natl Univ, Coll Med, Dept Physiol, Seoul, South Korea

[4] Korea Univ, Coll Med, Dept Anat, Seoul 136705, South Korea

[5] Univ Toronto, Fac Med, Dept Physiol, Toronto, ON M5S 1A8, Canada

[6] Korea Adv Inst Sci & Technol, Dept Biol Sci, Natl Creat Res Initiat Ctr Synaptogenesis, Taejon 305701, South Korea

[7] Kyungpook Natl Univ, Coll Ecol & Environm, Dept Appl Biol, Sangju Si, Kyeongbuk, South Korea

[8] Kyungpook Natl Univ, Sch Med, Dept Anat, Taegu, South Korea

[9] Sch Physiol & Pharmacol, MRC Ctr Synapt Plast, Bristol, Avon, England

来源：

NATURE NEUROSCIENCE | 2011年 / 14卷 / 11期

基金：

加拿大健康研究院;

关键词：

D-ASPARTATE RECEPTOR; SYNAPTIC PLASTICITY; PHOSPHATIDYLINOSITOL; 3-KINASE; PHOSPHOINOSITIDE; NOVELTY ACQUISITION; SIGNALING PATHWAY; IN-VITRO; KINASE; MEMORY; POTENTIATION;

D O I：

10.1038/nn.2937

中图分类号：

Q189 [神经科学];

学科分类号：

071006 [神经生物学];

摘要：

Phosphatidylinositol 3-kinase (PI3K) has been implicated in synaptic plasticity and other neural functions in the brain. However, the role of individual PI3K isoforms in the brain is unclear. We investigated the role of PI3K gamma in hippocampal-dependent synaptic plasticity and cognitive functions. We found that PI3K gamma has a crucial and specific role in NMDA receptor (NMDAR)-mediated synaptic plasticity at mouse Schaffer collateral-commissural synapses. Both genetic deletion and pharmacological inhibition of PI3K gamma disrupted NMDAR long-term depression (LTD) while leaving other forms of synaptic plasticity intact. Accompanying this physiological deficit, the impairment of NMDAR LTD by PI3K gamma blockade was specifically correlated with deficits in behavioral flexibility. These findings suggest that a specific PI3K isoform, PI3K gamma, is critical for NMDAR LTD and some forms of cognitive function. Thus, individual isoforms of PI3Ks may have distinct roles in different types of synaptic plasticity and may therefore influence various kinds of behavior.

引用

页码：1447 / U123

页数：10

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