title: Microtubule-associated protein tau is essential for long-term depression in the hippocampus.
abstract: The microtubule-associated protein tau is a principal component of neurofibrillary tangles, and has been identified as a key molecule in Alzheimer's disease and other tauopathies. However, it is unknown how a protein that is primarily located in axons is involved in a disease that is believed to have a synaptic origin. To investigate a possible synaptic function of tau, we studied synaptic plasticity in the hippocampus and found a selective deficit in long-term depression (LTD) in tau knockout mice in vivo and in vitro, an effect that was replicated by RNAi knockdown of tau in vitro. We found that the induction of LTD is associated with the glycogen synthase kinase-3-mediated phosphorylation of tau. These observations demonstrate that tau has a critical physiological function in LTD.
authors.affiliation: Department of Aging Neurobiology, Center for Development of Advanced Medicine for Dementia, National Center for Geriatrics and Gerontology, , 35 Gengo, Morioka, Obu, Aichi 474-8522, Japan.
authors.forename: Tetsuya
authors.initials: T
authors.lastname: Kimura
authors.forename: Daniel J
authors.initials: DJ
authors.lastname: Whitcomb
authors.forename: Jihoon
authors.initials: J
authors.lastname: Jo
authors.forename: Philip
authors.initials: P
authors.lastname: Regan
authors.forename: Thomas
authors.initials: T
authors.lastname: Piers
authors.forename: Seonghoo
authors.initials: S
authors.lastname: Heo
authors.forename: Christopher
authors.initials: C
authors.lastname: Brown
authors.forename: Tsutomu
authors.initials: T
authors.lastname: Hashikawa
authors.forename: Miyuki
authors.initials: M
authors.lastname: Murayama
authors.forename: Heon
authors.initials: H
authors.lastname: Seok
authors.forename: Ioannis
authors.initials: I
authors.lastname: Sotiropoulos
authors.forename: Eunjoon
authors.initials: E
authors.lastname: Kim
authors.forename: Graham L
authors.initials: GL
authors.lastname: Collingridge
authors.forename: Akihiko
authors.initials: A
authors.lastname: Takashima
authors.forename: Kwangwook
authors.initials: K
authors.lastname: Cho
mesh_terms: D000818:Animals; D015153:Blotting, Western; D038362:Glycogen Synthase Kinase 3 / Q000378:metabolism*; D006624:Hippocampus / Q000502:physiology*; D007150:Immunohistochemistry; D036881:Long-Term Synaptic Depression / Q000502:physiology*; D008297:Male; D051379:Mice; D008810:Mice, Inbred C57BL; D018345:Mice, Knockout; D042282:Microdissection; D008854:Microscopy, Electron; D010766:Phosphorylation; D034622:RNA Interference; D051381:Rats; D017208:Rats, Wistar; D013347:Subcellular Fractions; D013569:Synapses / Q000502:physiology*; D024801:Tauopathies / Q000503:physiopathology*; D016875:tau Proteins / Q000235:genetics / Q000378:metabolism*
chemical_list: C558298:Mapt protein, mouse; D016875:tau Proteins; D038362:Glycogen Synthase Kinase 3
keywords: Alzheimer's disease; hippocampus; long-term depression; synaptic plasticity; tau