title: Drebrin A regulates hippocampal LTP and hippocampus-dependent fear learning in adult mice.
abstract: Structural plasticity of dendritic spines, which underlies higher brain functions including learning and memory, is dynamically regulated by the actin cytoskeleton and its associated proteins. Drebrin A is an F-actin-binding protein preferentially expressed in the brain and localized in the dendritic spines of mature neurons. Isoform conversion from drebrin E to drebrin A and accumulation of the latter in dendritic spines occurs during synapse maturation. We have previously demonstrated that drebrin A plays a pivotal role in spine morphogenesis and plasticity. However, it is unclear whether drebrin A plays a specific role in processes required for structural plasticity, and whether drebrin E can substitute in this role. To answer these questions, we analyzed mutant mice (named DAKO mice), in which isoform conversion from drebrin E to drebrin A is disrupted. In DAKO mouse brain, drebrin E continues to be expressed throughout life instead of drebrin A. Electrophysiological studies using hippocampal slices revealed that long-term potentiation of CA1 synapses was impaired in adult DAKO mice, but not in adolescents. In parallel with this age-dependent impairment, DAKO mice exhibited impaired hippocampus-dependent fear learning in an age-dependent manner; the impairment was evident in adult mice, but not in adolescents. In addition, histological investigation revealed that the spine length of the apical dendrite of CA1 pyramidal cells was significantly longer in adult DAKO mice than in wild-type mice. Our data indicate that the roles of drebrin E and drebrin A in brain function are different from each other, that the isoform conversion of drebrin is critical, and that drebrin A is indispensable for normal synaptic plasticity and hippocampus-dependent fear memory in the adult brain.
authors.affiliation: Department of Neurobiology and Behavior, Gunma University Graduate School of Medicine, Maebashi, Gunma 371-8511, Japan; Faculty of Life Sciences, Toyo University, Itakura, Gunma 374-0193, Japan; Institute of Life Innovation Studies, Toyo University, Itakura, Gunma 374-0193, Japan.
authors.forename: N
authors.initials: N
authors.lastname: Kojima
authors.affiliation: Education and Research Support Center, Gunma University Graduate School of Medicine, Maebashi, Gunma 371-8511, Japan.
authors.forename: H
authors.initials: H
authors.lastname: Yasuda
authors.affiliation: Department of Neurobiology and Behavior, Gunma University Graduate School of Medicine, Maebashi, Gunma 371-8511, Japan.
authors.forename: K
authors.initials: K
authors.lastname: Hanamura
authors.affiliation: Department of Neurobiology and Behavior, Gunma University Graduate School of Medicine, Maebashi, Gunma 371-8511, Japan.
authors.forename: Y
authors.initials: Y
authors.lastname: Ishizuka
authors.affiliation: Department of Neurobiology and Behavior, Gunma University Graduate School of Medicine, Maebashi, Gunma 371-8511, Japan; Division of Pharmacology, National Institute of Health Sciences, Tokyo, Tokyo 158-8501, Japan.
authors.forename: Y
authors.initials: Y
authors.lastname: Sekino
authors.affiliation: Department of Neurobiology and Behavior, Gunma University Graduate School of Medicine, Maebashi, Gunma 371-8511, Japan. Electronic address: tshirao@gunma-u.ac.jp.
authors.forename: T
authors.initials: T
authors.lastname: Shirao
mesh_terms: D000375:Aging / Q000187:drug effects / Q000473:pathology / Q000502:physiology* / Q000523:psychology; D000818:Animals; D003213:Conditioning, Psychological / Q000502:physiology*; D003712:Dendrites / Q000187:drug effects / Q000473:pathology / Q000502:physiology; D019706:Excitatory Postsynaptic Potentials / Q000187:drug effects / Q000502:physiology; D005239:Fear / Q000502:physiology*; D006624:Hippocampus / Q000187:drug effects / Q000254:growth & development / Q000473:pathology / Q000502:physiology*; D017774:Long-Term Potentiation / Q000187:drug effects / Q000502:physiology*; D008297:Male; D008810:Mice, Inbred C57BL; D018345:Mice, Knockout; D009479:Neuropeptides / Q000235:genetics / Q000378:metabolism*; D020033:Protein Isoforms; D046509:Tissue Culture Techniques
chemical_list: D009479:Neuropeptides; D020033:Protein Isoforms; C053386:drebrins
keywords: drebrin A; drebrin E; fear learning; hippocampus; isoform conversion; synaptic plasticity