Activin Plays a Key Role in the Maintenance of Long-Term Memory and Late-LTP

• Published in: Learning & memory (Cold Spring Harbor, N.Y.) N.Y.), 2010-04, Vol.17 (4), p.176-185
• Main Authors: 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
• Format: Article
• Language: English
• Subjects: Animals; Behavior, Animal; Biochemistry; Biophysics; Brain; Calcium-Calmodulin-Dependent Protein Kinase Kinase - genetics; Conditioning (Psychology) - drug effects; Conditioning (Psychology) - physiology; Dentate Gyrus - drug effects; Dentate Gyrus - physiology; Doxycycline - administration & dosage; Electric Stimulation - methods; Enzyme Inhibitors - pharmacology; Enzyme-Linked Immunosorbent Assay - methods; Excitatory Postsynaptic Potentials - drug effects; Excitatory Postsynaptic Potentials - genetics; Fear; Follistatin - genetics; Follistatin - pharmacology; Functional Laterality; In Vitro Techniques; Inhibin-beta Subunits - genetics; Inhibin-beta Subunits - metabolism; Long Term Memory; Long-Term Potentiation - drug effects; Long-Term Potentiation - genetics; Long-Term Potentiation - physiology; Male; Memory - drug effects; Memory - physiology; Mice; Mice, Inbred C57BL; Mice, Transgenic; Prosencephalon - metabolism; Rats; Rats, Wistar; Short Term Memory
• ISSN: 1072-0502; 1549-5485
• DOI: 10.1101/lm.16659010

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 [beta]A, a member of the TGF-[beta] 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.