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 journalArticle (Academic Journal)peer-review

94 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 contributionPI3Kγ is required for NMDA receptor-dependent long-term depression and behavioral flexibility
Original languageEnglish
Pages (from-to)1447 - 1454
Number of pages7
JournalNature Neuroscience
Volume14
Issue number11
Early online date23 Oct 2011
DOIs
Publication statusPublished - Nov 2011

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