title: Learning-induced and stathmin-dependent changes in microtubule stability are critical for memory and disrupted in ageing.
abstract: 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.
authors.affiliation: 1] Department of Genetics, Rutgers University, Room 322 Life Sciences Building,145 Bevier Road, Piscataway, New Jersey 08854, USA [2] Division of Neuropsychiatry, Department of Neuroscience, Yamaguchi University Graduate School of Medicine, 1-1-1 Minami-Kogushi, Ube, Yamaguchi 755-8505, Japan [3].
authors.forename: Shusaku
authors.initials: S
authors.lastname: Uchida
authors.affiliation: 1] Department of Genetics, Rutgers University, Room 322 Life Sciences Building,145 Bevier Road, Piscataway, New Jersey 08854, USA [2].
authors.forename: Guillaume
authors.initials: G
authors.lastname: Martel
authors.affiliation: Department of Pathology, State University of New York, Downstate Medical Center, 450 Clarkson Avenue, Brooklyn, New York 11203, USA.
authors.forename: Alice
authors.initials: A
authors.lastname: Pavlowsky
authors.affiliation: Department of Genetics, Rutgers University, Room 322 Life Sciences Building,145 Bevier Road, Piscataway, New Jersey 08854, USA.
authors.forename: Shuichi
authors.initials: S
authors.lastname: Takizawa
authors.affiliation: Department of Genetics, Rutgers University, Room 322 Life Sciences Building,145 Bevier Road, Piscataway, New Jersey 08854, USA.
authors.forename: Charles
authors.initials: C
authors.lastname: Hevi
authors.affiliation: Division of Neuropsychiatry, Department of Neuroscience, Yamaguchi University Graduate School of Medicine, 1-1-1 Minami-Kogushi, Ube, Yamaguchi 755-8505, Japan.
authors.forename: Yoshifumi
authors.initials: Y
authors.lastname: Watanabe
authors.affiliation: Department of Neuroscience, Columbia University, Howard Hughes Medical Institute, Kavli Institute for Brain Science, 1051 Riverside Drive, New York, New York 10032, USA.
authors.forename: Eric R
authors.initials: ER
authors.lastname: Kandel
authors.affiliation: Department of Pathology, State University of New York, Downstate Medical Center, 450 Clarkson Avenue, Brooklyn, New York 11203, USA.
authors.forename: Juan Marcos
authors.initials: JM
authors.lastname: Alarcon
authors.affiliation: Department of Genetics, Rutgers University, Room 322 Life Sciences Building,145 Bevier Road, Piscataway, New Jersey 08854, USA.
authors.forename: Gleb P
authors.initials: GP
authors.lastname: Shumyatsky
mesh_terms: D000375:Aging / Q000502:physiology*; D000818:Animals; D006624:Hippocampus / Q000502:physiology / Q000503:physiopathology; D007858:Learning / Q000502:physiology*; D008297:Male; D008568:Memory / Q000502:physiology*; D008569:Memory Disorders / Q000503:physiopathology*; D051379:Mice; D008810:Mice, Inbred C57BL; D018345:Mice, Knockout; D008817:Mice, Mutant Strains; D008822:Mice, Transgenic; D008868:Microtubule Proteins / Q000502:physiology; D008870:Microtubules / Q000502:physiology*; D009154:Mutation / Q000235:genetics; D009473:Neuronal Plasticity / Q000502:physiology; D018091:Receptors, AMPA / Q000502:physiology; D015398:Signal Transduction / Q000502:physiology; D050777:Stathmin / Q000172:deficiency / Q000235:genetics / Q000502:physiology*; D014404:Tubulin / Q000502:physiology
chemical_list: D008868:Microtubule Proteins; D018091:Receptors, AMPA; D050777:Stathmin; D014404:Tubulin; C104722:glutamate receptor ionotropic, AMPA 2