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

J L Kim; H R Lee; S E Sim; J Baek; N K Yu; J H Choi; H G Ko; Y S Lee; S W Park; C Kwak; S J Ahn; S Y Choi; H Kim; K H Kim; P H Backx; C A Bradley; E Kim; D J Jang; K Lee; S J Kim; M Zhuo; GL Collingridge; B K Kaang

doi:10.1038/nn.2937

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

J L Kim, H R Lee, S E Sim, J Baek, N K Yu, J H Choi, H G Ko, Y S Lee, S W Park, C Kwak, S J Ahn, S Y Choi, H Kim, K H Kim, P H Backx, C A Bradley, E Kim, D J Jang, K Lee, S J KimM Zhuo, GL Collingridge, B K Kaang

Research output: Contribution to journal › Article (Academic Journal) › peer-review

127 Citations (Scopus)

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 PI3Kγ in hippocampal-dependent synaptic plasticity and cognitive functions. We found that PI3Kγ 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 PI3Kγ disrupted NMDAR long-term depression (LTD) while leaving other forms of synaptic plasticity intact. Accompanying this physiological deficit, the impairment of NMDAR LTD by PI3Kγ blockade was specifically correlated with deficits in behavioral flexibility. These findings suggest that a specific PI3K isoform, PI3Kγ, 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.

Translated title of the contribution	PI3Kγ is required for NMDA receptor-dependent long-term depression and behavioral flexibility
Original language	English
Pages (from-to)	1447 - 1454
Number of pages	7
Journal	Nature Neuroscience
Volume	14
Issue number	11
Early online date	23 Oct 2011
DOIs	https://doi.org/10.1038/nn.2937
Publication status	Published - Nov 2011

Access to Document

10.1038/nn.2937

http://www.nature.com/neuro/journal/v14/n11/full/nn.2937.html

Handle.net

Persistent link

Cite this

Kim, J. L., 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). PI3Kγ is required for NMDA receptor-dependent long-term depression and behavioral flexibility. Nature Neuroscience, 14(11), 1447 - 1454. https://doi.org/10.1038/nn.2937

@article{bf8f75a099f0449e9662344716984028,

title = "PI3Kγ is required for NMDA receptor-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 PI3Kγ in hippocampal-dependent synaptic plasticity and cognitive functions. We found that PI3Kγ 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 PI3Kγ disrupted NMDAR long-term depression (LTD) while leaving other forms of synaptic plasticity intact. Accompanying this physiological deficit, the impairment of NMDAR LTD by PI3Kγ blockade was specifically correlated with deficits in behavioral flexibility. These findings suggest that a specific PI3K isoform, PI3Kγ, 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, {J L} and Lee, {H R} and Sim, {S E} and J Baek and Yu, {N K} and Choi, {J H} and Ko, {H G} and Lee, {Y S} and Park, {S W} and C Kwak and Ahn, {S J} and Choi, {S Y} and H Kim and Kim, {K H} and Backx, {P H} and Bradley, {C A} and E Kim and Jang, {D J} and K Lee and Kim, {S J} and M Zhuo and GL Collingridge and Kaang, {B K}",

year = "2011",

month = nov,

doi = "10.1038/nn.2937",

language = "English",

volume = "14",

pages = "1447 -- 1454",

journal = "Nature Neuroscience",

issn = "1097-6256",

publisher = "Springer Nature",

number = "11",

}

Kim, JL, 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, 'PI3Kγ is required for NMDA receptor-dependent long-term depression and behavioral flexibility', Nature Neuroscience, vol. 14, no. 11, pp. 1447 - 1454. https://doi.org/10.1038/nn.2937

TY - JOUR

T1 - PI3Kγ is required for NMDA receptor-dependent long-term depression and behavioral flexibility

AU - Kim, J L

AU - Lee, H R

AU - Sim, S E

AU - Baek, J

AU - Yu, N K

AU - Choi, J H

AU - Ko, H G

AU - Lee, Y S

AU - Park, S W

AU - Kwak, C

AU - Ahn, S J

AU - Choi, S Y

AU - Kim, H

AU - Kim, K H

AU - Backx, P H

AU - Bradley, C A

AU - Kim, E

AU - Jang, D J

AU - Lee, K

AU - Kim, S J

AU - Zhuo, M

AU - Collingridge, GL

AU - Kaang, B K

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 PI3Kγ in hippocampal-dependent synaptic plasticity and cognitive functions. We found that PI3Kγ 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 PI3Kγ disrupted NMDAR long-term depression (LTD) while leaving other forms of synaptic plasticity intact. Accompanying this physiological deficit, the impairment of NMDAR LTD by PI3Kγ blockade was specifically correlated with deficits in behavioral flexibility. These findings suggest that a specific PI3K isoform, PI3Kγ, 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 PI3Kγ in hippocampal-dependent synaptic plasticity and cognitive functions. We found that PI3Kγ 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 PI3Kγ disrupted NMDAR long-term depression (LTD) while leaving other forms of synaptic plasticity intact. Accompanying this physiological deficit, the impairment of NMDAR LTD by PI3Kγ blockade was specifically correlated with deficits in behavioral flexibility. These findings suggest that a specific PI3K isoform, PI3Kγ, 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.

UR - http://www.scopus.com/inward/record.url?eid=2-s2.0-80054977111&partnerID=8YFLogxK

U2 - 10.1038/nn.2937

DO - 10.1038/nn.2937

M3 - Article (Academic Journal)

C2 - 22019731

SN - 1097-6256

VL - 14

SP - 1447

EP - 1454

JO - Nature Neuroscience

JF - Nature Neuroscience

IS - 11

ER -

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

Abstract

Access to Document

Handle.net

Other files and links

Fingerprint

MECHANISMS OF NMDA RECEPTOR DEPENDANT LTP AND LTD IN THE HIPPOCAMPUS

Cite this

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

Abstract

Access to Document

Handle.net

Other files and links

Fingerprint

Projects

MECHANISMS OF NMDA RECEPTOR DEPENDANT LTP AND LTD IN THE HIPPOCAMPUS

Cite this