Synapses that receive high levels of stimulation typically grow stronger. Lemieux et al. show that a protein complex that lands on microtubules near these active synapses permits them to be remodeled.
Neurons need a way to mark high-use synapses so they can attract the molecular raw material necessary to enhance the connections, which is manufactured far away in the body of the cell. One explanation, the so-called “synaptic tag and capture” hypothesis, suggests that the cell adds a label to the synapses that hooks passing raw material. What researchers don’t know is whether some factor also guides this material into active synapses. The CaMKII complex is a leading candidate for the synaptic tag. The complex is necessary for synaptic plasticity—mice lacking one of the four complex genes are slow learners—and CaMKII accumulates at active synapses, where calcium levels climb. But nobody had determined whether it also gathers inside nearby areas of the dendritic shaft, where calcium also increases.
Lemieux et al. found that CaMKII builds up in these neighboring portions of the dendrite. The complex adheres to microtubules in the dendrite and actively signals from there. CaMKII triggered nearby synapses to attract more receptors for the neurotransmitter glutamate, thus boosting synaptic sensitivity. Sections of the dendrite where CaMKII accumulated also sprouted more dendritic spines, the team revealed. Neurons carrying a version of CaMKII that can’t bind to microtubules didn’t show these changes. These results suggest that CaMKII fosters synaptic plasticity not only from its synaptic location but also from its position on dendritic microtubules. How CaMKII helps direct molecular cargoes to active synapses remains unclear.