PI3KÎ 3 is required for NMDA receptorg - Dependent long-term depression and behavioral flexibility

Jae Ick Kim; Hye Ryeon Lee; Su Eon Sim; Jinhee Baek; Nam Kyung Yu; Jun Hyeok Choi; Hyoung Gon Ko; Yong Seok Lee; Soo Won Park; Chuljung Kwak; Sung Ji Ahn; So Yoen Choi; Hyun Kim; Kyoung Han Kim; Peter H. Backx; Clarrisa A. Bradley; Eunjoon Kim; Deok Jin Jang; Kyungmin Lee; Sang Jeong Kim; Min Zhuo; Graham L. Collingridge; Bong Kiun Kaang

doi:10.1038/nn.2937

PI3KÎ 3 is required for NMDA receptorg - Dependent long-term depression and behavioral flexibility

Jae Ick Kim, Hye Ryeon Lee, Su Eon Sim, Jinhee Baek, Nam Kyung Yu, Jun Hyeok Choi, Hyoung Gon Ko, Yong Seok Lee, Soo Won Park, Chuljung Kwak, Sung Ji Ahn, So Yoen Choi, Hyun Kim, Kyoung Han Kim, Peter H. Backx, Clarrisa A. Bradley, Eunjoon Kim, Deok Jin Jang, Kyungmin Lee, Sang Jeong KimMin Zhuo, Graham L. Collingridge, Bong Kiun Kaang

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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 PI3KÎ 3 in hippocampal-dependent synaptic plasticity and cognitive functions. We found that PI3KÎ 3 has a crucial and specific role in NMDA receptor (NMDAR)-mediated synaptic plasticity at mouse Schaffer collateralg - commissural synapses. Both genetic deletion and pharmacological inhibition of PI3KÎ 3 disrupted NMDAR long-term depression (LTD) while leaving other forms of synaptic plasticity intact. Accompanying this physiological deficit, the impairment of NMDAR LTD by PI3KÎ 3 blockade was specifically correlated with deficits in behavioral flexibility. These findings suggest that a specific PI3K isoform, PI3KÎ 3, 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.

Original language	English
Pages (from-to)	1447-1454
Number of pages	8
Journal	Nature Neuroscience
Volume	14
Issue number	11
DOIs	https://doi.org/10.1038/nn.2937
State	Published - Nov 2011

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Kim, J. I., Lee, H. R., Sim, S. E., Baek, J., Yu, N. K., Choi, J. H., Ko, H. G., Lee, Y. S., Park, S. W., Kwak, C., Ahn, S. J., Choi, S. Y., Kim, H., Kim, K. H., Backx, P. H., Bradley, C. A., Kim, E., Jang, D. J., Lee, K., ... Kaang, B. K. (2011). PI3KÎ 3 is required for NMDA receptorg - Dependent long-term depression and behavioral flexibility. Nature Neuroscience, 14(11), 1447-1454. https://doi.org/10.1038/nn.2937

@article{634e0ca21451426c941320ed6610a2a7,

title = "PI3K{\^I} 3 is required for NMDA receptorg - Dependent long-term depression and behavioral flexibility",

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{\^I} 3 in hippocampal-dependent synaptic plasticity and cognitive functions. We found that PI3K{\^I} 3 has a crucial and specific role in NMDA receptor (NMDAR)-mediated synaptic plasticity at mouse Schaffer collateralg - commissural synapses. Both genetic deletion and pharmacological inhibition of PI3K{\^I} 3 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{\^I} 3 blockade was specifically correlated with deficits in behavioral flexibility. These findings suggest that a specific PI3K isoform, PI3K{\^I} 3, 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.",

author = "Kim, {Jae Ick} and Lee, {Hye Ryeon} and Sim, {Su Eon} and Jinhee Baek and Yu, {Nam Kyung} and Choi, {Jun Hyeok} and Ko, {Hyoung Gon} and Lee, {Yong Seok} and Park, {Soo Won} and Chuljung Kwak and Ahn, {Sung Ji} and Choi, {So Yoen} and Hyun Kim and Kim, {Kyoung Han} and Backx, {Peter H.} and Bradley, {Clarrisa A.} and Eunjoon Kim and Jang, {Deok Jin} and Kyungmin Lee and Kim, {Sang Jeong} and Min Zhuo and Collingridge, {Graham L.} and Kaang, {Bong Kiun}",

year = "2011",

month = nov,

doi = "10.1038/nn.2937",

language = "English",

volume = "14",

pages = "1447--1454",

journal = "Nature Neuroscience",

issn = "1097-6256",

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Kim, JI, Lee, HR, Sim, SE, Baek, J, Yu, NK, Choi, JH, Ko, HG, Lee, YS, Park, SW, Kwak, C, Ahn, SJ, Choi, SY, Kim, H, Kim, KH, Backx, PH, Bradley, CA, Kim, E, Jang, DJ , Lee, K, Kim, SJ, Zhuo, M, Collingridge, GL & Kaang, BK 2011, 'PI3KÎ 3 is required for NMDA receptorg - Dependent long-term depression and behavioral flexibility', Nature Neuroscience, vol. 14, no. 11, pp. 1447-1454. https://doi.org/10.1038/nn.2937

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T1 - PI3KÎ 3 is required for NMDA receptorg - Dependent long-term depression and behavioral flexibility

AU - Kim, Jae Ick

AU - Lee, Hye Ryeon

AU - Sim, Su Eon

AU - Baek, Jinhee

AU - Yu, Nam Kyung

AU - Choi, Jun Hyeok

AU - Ko, Hyoung Gon

AU - Lee, Yong Seok

AU - Park, Soo Won

AU - Kwak, Chuljung

AU - Ahn, Sung Ji

AU - Choi, So Yoen

AU - Kim, Hyun

AU - Kim, Kyoung Han

AU - Backx, Peter H.

AU - Bradley, Clarrisa A.

AU - Kim, Eunjoon

AU - Jang, Deok Jin

AU - Lee, Kyungmin

AU - Kim, Sang Jeong

AU - Zhuo, Min

AU - Collingridge, Graham L.

AU - Kaang, Bong Kiun

PY - 2011/11

Y1 - 2011/11

N2 - 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 PI3KÎ 3 in hippocampal-dependent synaptic plasticity and cognitive functions. We found that PI3KÎ 3 has a crucial and specific role in NMDA receptor (NMDAR)-mediated synaptic plasticity at mouse Schaffer collateralg - commissural synapses. Both genetic deletion and pharmacological inhibition of PI3KÎ 3 disrupted NMDAR long-term depression (LTD) while leaving other forms of synaptic plasticity intact. Accompanying this physiological deficit, the impairment of NMDAR LTD by PI3KÎ 3 blockade was specifically correlated with deficits in behavioral flexibility. These findings suggest that a specific PI3K isoform, PI3KÎ 3, 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.

AB - 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 PI3KÎ 3 in hippocampal-dependent synaptic plasticity and cognitive functions. We found that PI3KÎ 3 has a crucial and specific role in NMDA receptor (NMDAR)-mediated synaptic plasticity at mouse Schaffer collateralg - commissural synapses. Both genetic deletion and pharmacological inhibition of PI3KÎ 3 disrupted NMDAR long-term depression (LTD) while leaving other forms of synaptic plasticity intact. Accompanying this physiological deficit, the impairment of NMDAR LTD by PI3KÎ 3 blockade was specifically correlated with deficits in behavioral flexibility. These findings suggest that a specific PI3K isoform, PI3KÎ 3, 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.

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U2 - 10.1038/nn.2937

DO - 10.1038/nn.2937

M3 - Article

C2 - 22019731

AN - SCOPUS:80054977111

SN - 1097-6256

VL - 14

SP - 1447

EP - 1454

JO - Nature Neuroscience

JF - Nature Neuroscience

IS - 11

ER -

PI3KÎ 3 is required for NMDA receptorg - Dependent long-term depression and behavioral flexibility

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