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Microtubule-associated protein tau is essential for long-term depression in the hippocampus
Kimura, Tetsuya,Whitcomb, Daniel J.,Jo, Jihoon,Regan, Philip,Piers, Thomas,Heo, Seonghoo,Brown, Christopher,Hashikawa, Tsutomu,Murayama, Miyuki,Seok, Heon,Sotiropoulos, Ioannis,Kim, Eunjoon,Collingrid The Royal Society 2014 Philosophical transactions. Biological sciences Vol.369 No.1633
<P>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 <I>in vivo</I> and <I>in vitro</I>, an effect that was replicated by RNAi knockdown of tau <I>in vitro</I>. 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.</P>