Stable isotope labeling was used to measure dynamics of tubulin incorporation into microtubule subpopulations representing different neuronal compartments in the murine hippocampus. Neuronal microtubules were largely static. Basal turnover was highest in tau-associated (axona) and growth cone), lower in MAP2-associated (somatodendritic), and lowest in cold stable (axonal shaft) subpopulations. Intracerebroventricular glutamate injection stimulated label incorporation into axonal shaft and somatodendritic microtubules, the latter dependent on cAMP-PKA. Hippocampus-dependent memory formation after contextual fear conditioning was accompanied by increased assembly of MAP2- and cold stable-microtubules. Both microtubule assembly and memory formation were inhibited by the microtubule depolymerizing drug, nocodazole. This approach allows for correlation with behavioral measures of learning and memory and for the screening of candidate agents for stimulatory activities on learning memory.
