Effects of PI3Kγ overexpression in the hippocampus on synaptic plasticity and spatial learning.

Effects of PI3Kγ overexpression in the hippocampus on synaptic plasticity and spatial learning.
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DOI:
10.1186/s13041-014-0078-6
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发表时间:
2014-11-06
期刊:
影响因子:
3.6
通讯作者:
Kaang BK
Kaang BK
中科院分区:
医学3区
文献类型:
--
作者:
Choi JH;Park P;Baek GC;Sim SE;Kang SJ;Lee Y;Ahn SH;Lim CS;Lee YS;Collingridge GL;Kaang BK

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先前的研究表明,磷酸肌醇3-激酶(PI 3 Ks)家族在大脑中起着关键作用;特别是,我们先前报道了敲除小鼠中PI 3 K的γ亚型(PI 3 K γ)会损害突触可塑性并降低行为灵活性。为了进一步研究PI 3 K γ在突触可塑性和海马依赖性行为任务中的作用,我们在海马CA 1区过表达PI 3 K γ的催化亚基p110γ。我们发现p110γ的过度表达损害了NMDA受体依赖的长时程抑郁(LTD)和Morris水迷宫(MWM)任务中的海马区依赖的空间学习。相反,长时程增强(LTP)和背景恐惧记忆不受p110γ过表达的影响。这些结果与先前的敲除研究一起表明,海马中PI 3 K γ的临界水平是成功诱导LTD和正常学习所必需的。
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.
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