Dynamic microtubules are important to maintain neuronal morphology and function, but whether neuronal activity affects the organization of dynamic microtubules is unknown. Here, we show that a protocol to induce NMDA-dependent long-term depression (LTD) rapidly attenuates microtubule dynamics in primary rat hippocampal neurons, removing the microtubule-binding protein EB3 from the growing microtubule plus-ends in dendrites. This effect requires the entry of calcium and is mediated by activation of NR2B-containing NMDA-type glutamate receptor. The rapid NMDA effect is followed by a second, more prolonged response, during which EB3 accumulates along MAP2-positive microtubule bundles in the dendritic shaft. MAP2 is both required and sufficient for this activity-dependent redistribution of EB3. Importantly,NMDAreceptor activation suppresses microtubule entry in dendritic spines, whereas overexpression of EB3-GFP prevents NMDA-induced spine shrinkage. These results suggest that short-lasting and long-lasting changes in dendriticmicrotubule dynamics are important determinants for NMDA-induced LTD.

doi.org/10.1523/JNEUROSCI.6215-10.2011, hdl.handle.net/1765/33771
The Journal of Neuroscience
Erasmus MC: University Medical Center Rotterdam

Kapitein, L.C, Yau, K.W, Gouveia, S.M, van der Zwan, W.A, Wulf, P, Keijzer, N, … Hoogenraad, C.C. (2011). NMDA receptor activation suppresses microtubule growth and spine entry. The Journal of Neuroscience, 31(22), 8194–8209. doi:10.1523/JNEUROSCI.6215-10.2011