Effects of PI3Kγ overexpression in the hippocampus on synaptic plasticity and spatial learning.
Previous studies have shown that a family of phosphoinositide 3-kinases (PI3Ks) plays pivotal roles in the brain; in particular, we previously reported that knockout of the γ isoform of PI3K (PI3Kγ) in mice impaired synaptic plasticity and reduced behavioral flexibility. To further examine the role of PI3Kγ in synaptic plasticity and hippocampus-dependent behavioral tasks we overexpressed p110γ, the catalytic subunit of PI3Kγ, in the hippocampal CA1 region. We found that the overexpression of p110γ impairs NMDA receptor-dependent long-term depression (LTD) and hippocampus-dependent spatial learning in the Morris water maze (MWM) task. In contrast, long-term potentiation (LTP) and contextual fear memory were not affected by p110γ overexpression. These results, together with the previous knockout study, suggest that a critical level of PI3Kγ in the hippocampus is required for successful induction of LTD and normal learning.
Jun-Hyeok
JH
Choi
Pojeong
P
Park
Gi-Chul
GC
Baek
Su-Eon
SE
Sim
SukJae Joshua
SJ
Kang
Yeseul
Y
Lee
Seo-Hee
SH
Ahn
Chae-Seok
CS
Lim
Yong-Seok
YS
Lee
Graham L
GL
Collingridge
Bong-Kiun
BK
Kaang
D000818:Animals; D001007:Anxiety / Q000503:physiopathology; D056547:CA1 Region, Hippocampal / Q000378:metabolism; D058534:Class I Phosphatidylinositol 3-Kinases / Q000378:metabolism*; D057809:HEK293 Cells; D006624:Hippocampus / Q000201:enzymology* / Q000503:physiopathology; D006801:Humans; D036881:Long-Term Synaptic Depression; D008297:Male; D018782:Maze Learning; D008810:Mice, Inbred C57BL; D009043:Motor Activity; D009473:Neuronal Plasticity; D016194:Receptors, N-Methyl-D-Aspartate / Q000378:metabolism; D065853:Spatial Learning; D013647:Task Performance and Analysis; D048051:p38 Mitogen-Activated Protein Kinases / Q000378:metabolism
D016194:Receptors, N-Methyl-D-Aspartate; C509622:1-phosphatidylinositol 3-kinase p110 subunit, mouse; D058534:Class I Phosphatidylinositol 3-Kinases; D048051:p38 Mitogen-Activated Protein Kinases