Activin plays a key role in the maintenance of long-term memory and late-LTP

Hiroshi Ageta, Shiro Ikegami, Masami Miura, Masao Masuda, Rika Migishima, Toshiaki Hino, Noriko Takashima, Akiko Murayama, Hiromu Sugino, Mitsutoshi Setou, Satoshi Kida, Minesuke Yokoyama, Yoshihisa Hasegawa, Kunihiro Tsuchida, Toshihiko Aosaki, Kaoru Inokuchi

Research output: Contribution to journalArticle

32 Citations (Scopus)

Abstract

A recent study has revealed that fear memory may be vulnerable following retrieval, and is then reconsolidated in a protein synthesis-dependent manner. However, little is known about the molecular mechanisms of these processes. Activin βA, a member of the TGF-β superfamily, is increased in activated neuronal circuits and regulates dendritic spine morphology. To clarify the role of activin in the synaptic plasticity of the adult brain, we examined the effect of inhibiting or enhancing activin function on hippocampal long-term potentiation (LTP). We found that follistatin, a specific inhibitor of activin, blocked the maintenance of late LTP (L-LTP) in the hippocampus. In contrast, administration of activin facilitated the maintenance of early LTP (E-LTP). We generated forebrain-specific activin- or follistatin-transgenic mice in which transgene expression is under the control of the Tet-OFF system. Maintenance of hippocampal L-LTP was blocked in the follistatin-transgenic mice. In the contextual fear-conditioning test, we found that follistatin blocked the formation of long-term memory (LTM) without affecting short-term memory (STM). Furthermore, consolidated memory was selectively weakened by the expression of follistatin during retrieval, but not during the maintenance phase. On the other hand, the maintenance of memory was also influenced by activin overexpression during the retrieval phase. Thus, the level of activin in the brain during the retrieval phase plays a key role in the maintenance of long-term memory.

Original languageEnglish
Pages (from-to)176-185
Number of pages10
JournalLearning and Memory
Volume17
Issue number4
DOIs
Publication statusPublished - 01-04-2010

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Activins
Long-Term Memory
Long-Term Potentiation
Follistatin
Maintenance
Transgenic Mice
Fear
Dendritic Spines
Neuronal Plasticity
Brain
Prosencephalon
Transgenes
Short-Term Memory
Hippocampus

All Science Journal Classification (ASJC) codes

  • Neuropsychology and Physiological Psychology
  • Cognitive Neuroscience
  • Cellular and Molecular Neuroscience

Cite this

Ageta, H., Ikegami, S., Miura, M., Masuda, M., Migishima, R., Hino, T., ... Inokuchi, K. (2010). Activin plays a key role in the maintenance of long-term memory and late-LTP. Learning and Memory, 17(4), 176-185. https://doi.org/10.1101/lm.16659010
Ageta, Hiroshi ; Ikegami, Shiro ; Miura, Masami ; Masuda, Masao ; Migishima, Rika ; Hino, Toshiaki ; Takashima, Noriko ; Murayama, Akiko ; Sugino, Hiromu ; Setou, Mitsutoshi ; Kida, Satoshi ; Yokoyama, Minesuke ; Hasegawa, Yoshihisa ; Tsuchida, Kunihiro ; Aosaki, Toshihiko ; Inokuchi, Kaoru. / Activin plays a key role in the maintenance of long-term memory and late-LTP. In: Learning and Memory. 2010 ; Vol. 17, No. 4. pp. 176-185.
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Ageta, H, Ikegami, S, Miura, M, Masuda, M, Migishima, R, Hino, T, Takashima, N, Murayama, A, Sugino, H, Setou, M, Kida, S, Yokoyama, M, Hasegawa, Y, Tsuchida, K, Aosaki, T & Inokuchi, K 2010, 'Activin plays a key role in the maintenance of long-term memory and late-LTP', Learning and Memory, vol. 17, no. 4, pp. 176-185. https://doi.org/10.1101/lm.16659010

Activin plays a key role in the maintenance of long-term memory and late-LTP. / Ageta, Hiroshi; Ikegami, Shiro; Miura, Masami; Masuda, Masao; Migishima, Rika; Hino, Toshiaki; Takashima, Noriko; Murayama, Akiko; Sugino, Hiromu; Setou, Mitsutoshi; Kida, Satoshi; Yokoyama, Minesuke; Hasegawa, Yoshihisa; Tsuchida, Kunihiro; Aosaki, Toshihiko; Inokuchi, Kaoru.

In: Learning and Memory, Vol. 17, No. 4, 01.04.2010, p. 176-185.

Research output: Contribution to journalArticle

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T1 - Activin plays a key role in the maintenance of long-term memory and late-LTP

AU - Ageta, Hiroshi

AU - Ikegami, Shiro

AU - Miura, Masami

AU - Masuda, Masao

AU - Migishima, Rika

AU - Hino, Toshiaki

AU - Takashima, Noriko

AU - Murayama, Akiko

AU - Sugino, Hiromu

AU - Setou, Mitsutoshi

AU - Kida, Satoshi

AU - Yokoyama, Minesuke

AU - Hasegawa, Yoshihisa

AU - Tsuchida, Kunihiro

AU - Aosaki, Toshihiko

AU - Inokuchi, Kaoru

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N2 - A recent study has revealed that fear memory may be vulnerable following retrieval, and is then reconsolidated in a protein synthesis-dependent manner. However, little is known about the molecular mechanisms of these processes. Activin βA, a member of the TGF-β superfamily, is increased in activated neuronal circuits and regulates dendritic spine morphology. To clarify the role of activin in the synaptic plasticity of the adult brain, we examined the effect of inhibiting or enhancing activin function on hippocampal long-term potentiation (LTP). We found that follistatin, a specific inhibitor of activin, blocked the maintenance of late LTP (L-LTP) in the hippocampus. In contrast, administration of activin facilitated the maintenance of early LTP (E-LTP). We generated forebrain-specific activin- or follistatin-transgenic mice in which transgene expression is under the control of the Tet-OFF system. Maintenance of hippocampal L-LTP was blocked in the follistatin-transgenic mice. In the contextual fear-conditioning test, we found that follistatin blocked the formation of long-term memory (LTM) without affecting short-term memory (STM). Furthermore, consolidated memory was selectively weakened by the expression of follistatin during retrieval, but not during the maintenance phase. On the other hand, the maintenance of memory was also influenced by activin overexpression during the retrieval phase. Thus, the level of activin in the brain during the retrieval phase plays a key role in the maintenance of long-term memory.

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