Details

Autor(en) / Beteiligte

• Uchida, Shusaku
• Martel, Guillaume
• Pavlowsky, Alice
• Takizawa, Shuichi
• Hevi, Charles
• Watanabe, Yoshifumi
• Kandel, Eric R.
• Alarcon, Juan Marcos
• Shumyatsky, Gleb P.

Titel

Learning-induced and stathmin-dependent changes in microtubule stability are critical for memory and disrupted in ageing

Ist Teil von

• Nature communications, 2014-07, Vol.5 (1), p.4389-4389, Article 4389

Ort / Verlag

London: Nature Publishing Group UK

Erscheinungsjahr

2014

Quelle

MEDLINE

Beschreibungen/Notizen

• Changes in the stability of microtubules regulate many biological processes, but their role in memory remains unclear. Here we show that learning causes biphasic changes in the microtubule-associated network in the hippocampus. In the early phase, stathmin is dephosphorylated, enhancing its microtubule-destabilizing activity by promoting stathmin-tubulin binding, whereas in the late phase these processes are reversed leading to an increase in microtubule/KIF5-mediated localization of the GluA2 subunit of AMPA receptors at synaptic sites. A microtubule stabilizer paclitaxel decreases or increases memory when applied at the early or late phases, respectively. Stathmin mutations disrupt changes in microtubule stability, GluA2 localization, synaptic plasticity and memory. Aged wild-type mice show impairments in stathmin levels, changes in microtubule stability and GluA2 localization. Blocking GluA2 endocytosis rescues memory deficits in stathmin mutant and aged wild-type mice. These findings demonstrate a role for microtubules in memory in young adult and aged individuals. The microtubule-associated protein stathmin is implicated in cognitive processing but it is unclear how. Here, the authors show that stathmin regulates microtubule stability and dendritic transport of specific AMPA receptor subunits, and that this regulation is impaired in aged mice.