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- Title
PI3K? is required for NMDA receptor-dependent long-term depression and behavioral flexibility.
- Authors
Kim, Jae-Ick; Lee, Hye-Ryeon; Sim, Su-eon; Baek, Jinhee; Yu, Nam-Kyung; Choi, Jun-Hyeok; Ko, Hyoung-Gon; Lee, Yong-Seok; Park, Soo-Won; Kwak, Chuljung; Ahn, Sung-Ji; Choi, So Yoen; Kim, Hyun; Kim, Kyoung-Han; Backx, Peter H; Bradley, Clarrisa A; Kim, Eunjoon; Jang, Deok-Jin; Lee, Kyungmin; Kim, Sang Jeong
- Abstract
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? in hippocampal-dependent synaptic plasticity and cognitive functions. We found that PI3K? 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? 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? blockade was specifically correlated with deficits in behavioral flexibility. These findings suggest that a specific PI3K isoform, PI3K?, 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.
- Subjects
PHOSPHOINOSITIDES; NEUROPLASTICITY; SYNAPSES; METHYL aspartate; COGNITIVE ability; BRAIN
- Publication
Nature Neuroscience, 2011, Vol 14, Issue 11, p1447
- ISSN
1097-6256
- Publication type
Article
- DOI
10.1038/nn.2937