Phosphatidylinositol 4-phosphate (PI4P) is a low abundant phospholipid with important roles in lipid transport and membrane trafficking. However, little is known of its metabolism and function in neurons. Here, we investigate its subcellular distribution and functional roles in dendrites of rodent hippocampal neurons during resting state and long-term synaptic potentiation (LTP). We show that neural activity causes dynamic reversible changes in PI4P metabolism in dendrites. Upon LTP induction, PI4KIIIα, a type III phosphatidylinositol 4-kinase, localizes to the dendritic plasma membrane (PM) in a calcium-dependent manner and causes substantial increase in the levels of PI4P. Acute inhibition of PI4KIIIα activity abolishes trafficking of the AMPA-type glutamate receptor to the PM during LTP induction, and silencing of PI4KIIIα expression in the hippocampal CA1 region causes severe impairment of LTP and long-term memory. Collectively, our results identify an essential role for PI4KIIIα-dependent PI4P synthesis in synaptic plasticity of central nervous system neurons.

4-磷酸磷脂酰肌醇 (PI4P) 是一种低丰度的磷脂，在脂质转运和膜运输中具有重要作用。然而，对其在神经元中的代谢和功能知之甚少。在这里，我们研究了它在静息状态和长期突触增强 (LTP) 期间在啮齿动物海马神经元树突中的亚细胞分布和功能作用。我们表明神经活动导致树突中 PI4P 代谢的动态可逆变化。在 LTP 诱导后，一种 III 型磷脂酰肌醇 4-激酶 PI4KIIIα 以钙依赖性方式定位于树突质膜 (PM) 并导致 PI4P 水平显着增加。PI4KIIIα 活性的急性抑制消除了 LTP 诱导期间 AMPA 型谷氨酸受体向 PM 的运输，海马 CA1 区 PI4KIIIα 表达的沉默导致 LTP 和长期记忆的严重损害。总的来说，我们的结果确定了 PI4KIIIα 依赖性 PI4P 合成在中枢神经系统神经元突触可塑性中的重要作用。