title: Acute modulation of synaptic plasticity of pyramidal neurons by activin in adult hippocampus.
abstract: Activin A is known as a neuroprotective factor produced upon acute excitotoxic injury of the hippocampus (in pathological states). We attempt to reveal the role of activin as a neuromodulator in the adult male hippocampus under physiological conditions (in healthy states), which remains largely unknown. We showed endogenous/basal expression of activin in the hippocampal neurons. Localization of activin receptors in dendritic spines (=postsynapses) was demonstrated by immunoelectron microscopy. The incubation of hippocampal acute slices with activin A (10 ng/mL, 0.4 nM) for 2 h altered the density and morphology of spines in CA1 pyramidal neurons. The total spine density increased by 1.2-fold upon activin treatments. Activin selectively increased the density of large-head spines, without affecting middle-head and small-head spines. Blocking Erk/MAPK, PKA, or PKC prevented the activin-induced spinogenesis by reducing the density of large-head spines, independent of Smad-induced gene transcription which usually takes more than several hours. Incubation of acute slices with activin for 2 h induced the moderate early long-term potentiation (moderate LTP) upon weak theta burst stimuli. This moderate LTP induction was blocked by follistatin, MAPK inhibitor (PD98059) and inhibitor of NR2B subunit of NMDA receptors (Ro25-6981). It should be noted that the weak theta burst stimuli alone cannot induce moderate LTP. These results suggest that MAPK-induced phosphorylation of NMDA receptors (including NR2B) may play an important role for activin-induced moderate LTP. Taken together, the current results reveal interesting physiological roles of endogenous activin as a rapid synaptic modulator in the adult hippocampus.
authors.affiliation: Department of Biophysics and Life Sciences, Graduate School of Arts and Sciences, The University of Tokyo Meguro, Japan.
authors.forename: Yoshitaka
authors.initials: Y
authors.lastname: Hasegawa
authors.affiliation: Department of Biophysics and Life Sciences, Graduate School of Arts and Sciences, The University of Tokyo Meguro, Japan ; Bioinformatics Project (BIRD), Japan Science and Technology Agency, The University of Tokyo Meguro, Japan ; Core Research for Evolutional Science and Technology Project of Japan Science and Technology Agency, The University of Tokyo Meguro, Japan ; Department of Computer Science, School of Science and Technology, Meiji University Kawasaki, Japan.
authors.forename: Hideo
authors.initials: H
authors.lastname: Mukai
authors.affiliation: Department of Biophysics and Life Sciences, Graduate School of Arts and Sciences, The University of Tokyo Meguro, Japan.
authors.forename: Makoto
authors.initials: M
authors.lastname: Asashima
authors.affiliation: Department of Biophysics and Life Sciences, Graduate School of Arts and Sciences, The University of Tokyo Meguro, Japan ; Bioinformatics Project (BIRD), Japan Science and Technology Agency, The University of Tokyo Meguro, Japan ; Core Research for Evolutional Science and Technology Project of Japan Science and Technology Agency, The University of Tokyo Meguro, Japan.
authors.forename: Yasushi
authors.initials: Y
authors.lastname: Hojo
authors.affiliation: Department of Biophysics and Life Sciences, Graduate School of Arts and Sciences, The University of Tokyo Meguro, Japan.
authors.forename: Muneki
authors.initials: M
authors.lastname: Ikeda
authors.affiliation: Department of Biophysics and Life Sciences, Graduate School of Arts and Sciences, The University of Tokyo Meguro, Japan.
authors.forename: Yoshimasa
authors.initials: Y
authors.lastname: Komatsuzaki
authors.affiliation: Department of Biophysics and Life Sciences, Graduate School of Arts and Sciences, The University of Tokyo Meguro, Japan.
authors.forename: Yuuki
authors.initials: Y
authors.lastname: Ooishi
authors.affiliation: Department of Biophysics and Life Sciences, Graduate School of Arts and Sciences, The University of Tokyo Meguro, Japan ; Bioinformatics Project (BIRD), Japan Science and Technology Agency, The University of Tokyo Meguro, Japan ; Core Research for Evolutional Science and Technology Project of Japan Science and Technology Agency, The University of Tokyo Meguro, Japan ; National MEXT Project in Special Coordinate Funds for Promoting Science and Technology, The University of Tokyo Meguro, Japan.
authors.forename: Suguru
authors.initials: S
authors.lastname: Kawato
mesh_terms: D029404:Activin Receptors / Q000235:genetics / Q000378:metabolism*; D028341:Activins / Q000235:genetics / Q000378:metabolism* / Q000494:pharmacology; D000818:Animals; D049229:Dendritic Spines / Q000187:drug effects / Q000378:metabolism; D006624:Hippocampus / Q000187:drug effects / Q000378:metabolism*; D008297:Male; D009473:Neuronal Plasticity / Q000187:drug effects / Q000502:physiology*; D010766:Phosphorylation / Q000187:drug effects / Q000502:physiology; D017966:Pyramidal Cells / Q000187:drug effects / Q000378:metabolism*; D051381:Rats; D017208:Rats, Wistar; D016194:Receptors, N-Methyl-D-Aspartate / Q000235:genetics / Q000378:metabolism; D015398:Signal Transduction / Q000187:drug effects / Q000502:physiology
chemical_list: D016194:Receptors, N-Methyl-D-Aspartate; C422405:activin A; D028341:Activins; D029404:Activin Receptors
keywords: LTP; activin; hippocampus; kinase; rapid effect; spine; synapse