PI3Kγ is required for NMDA receptor-dependent long-term depression and behavioral flexibility.
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.
National Creative Research Initiative Center for Memory, Department of Biological Sciences, College of Natural Sciences, Seoul National University, Seoul, Korea.
Jae-Ick
JI
Kim
Hye-Ryeon
HR
Lee
Su-eon
SE
Sim
Jinhee
J
Baek
Nam-Kyung
NK
Yu
Jun-Hyeok
JH
Choi
Hyoung-Gon
HG
Ko
Yong-Seok
YS
Lee
Soo-Won
SW
Park
Chuljung
C
Kwak
Sung-Ji
SJ
Ahn
So Yoen
SY
Choi
Hyun
H
Kim
Kyoung-Han
KH
Kim
Peter H
PH
Backx
Clarrisa A
CA
Bradley
Eunjoon
E
Kim
Deok-Jin
DJ
Jang
Kyungmin
K
Lee
Sang Jeong
SJ
Kim
Min
M
Zhuo
Graham L
GL
Collingridge
Bong-Kiun
BK
Kaang
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