National Creative Research Initiative Center for Memory, Department of Biological Sciences, College of Natural Sciences, Seoul National University, Seoul, Korea.
Nat Neurosci. 2011 Oct 23;14(11):1447-54. doi: 10.1038/nn.2937.
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.
磷酸肌醇 3-激酶 (PI3K) 已被牵涉到大脑中的突触可塑性和其他神经功能。然而，单个 PI3K 同工型在大脑中的作用尚不清楚。我们研究了 PI3Kγ 在海马依赖性突触可塑性和认知功能中的作用。我们发现 PI3Kγ 在小鼠 Schaffer 侧枝-联合突触的 NMDA 受体 (NMDAR) 介导的突触可塑性中具有关键和特定的作用。PI3Kγ 的遗传缺失和药理学抑制都破坏了 NMDAR 长时程抑制 (LTD)，而其他形式的突触可塑性则保持完整。伴随着这种生理缺陷，PI3Kγ 阻断引起的 NMDAR LTD 损伤与行为灵活性的缺陷特异性相关。这些发现表明，特定的 PI3K 同工型 PI3Kγ 对于 NMDAR LTD 和某些形式的认知功能至关重要。因此，PI3Ks 的单个同工型可能在不同类型的突触可塑性中具有不同的作用，因此可能会影响各种行为。
