Abstract
In neurons, microtubules form dense bundles and run along the length of axons and dendrites. Occasionally, dendritic microtubules can grow from the shaft directly into dendritic spines. Microtubules target dendritic spines that are undergoing activity-dependent changes, but the mechanism by which microtubules enter spines has remained poorly understood. Using live-cell imaging, high-resolution microscopy, and local glutamate uncaging, we show that local actin remodeling at the base of a spine promotes microtubule spine targeting. Microtubule spine entry is triggered by activation of N-Methyl-D-aspartic acid (NMDA) receptors and calcium influx and requires dynamic actin remodeling. Activity-dependent translocation of the actin remodeling protein cortactin out of the spine correlates with increased microtubule targeting at a single spine level. Our data show that the structural changes in the actin cytoskeleton at the base of the spine are directly involved in microtubule entry and emphasize the importance of actin-microtubule crosstalk in orchestrating synapse function and plasticity.