Activity-dependent PI4P synthesis by PI4KIIIα regulates long-term synaptic potentiation

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, PI4KIII alpha, 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 PI4KIII alpha activity abolishes trafficking of the AMPA-type glutamate receptor to the PM during LTP induction, and silencing of PI4KIII alpha expression in the hippocampal CA1 region causes severe impairment of LTP and long-term memory. Collectively, our results identify an essential role for PI4KIII alpha-dependent PI4P synthesis in synaptic plasticity of central nervous system neurons.

Automated summary

This study reveals the important role of phosphatidylinositol 4-phosphate (PI4P) in neuronal function, particularly in synaptic plasticity. The levels of PI4P increase significantly during long-term synaptic potentiation (LTP), and inhibition of PI4KIII alpha activity during LTP induction impairs LTP and long-term memory.