title: BAF53b, a Neuron-Specific Nucleosome Remodeling Factor, Is Induced after Learning and Facilitates Long-Term Memory Consolidation.
abstract: Although epigenetic mechanisms of gene expression regulation have recently been implicated in memory consolidation and persistence, the role of nucleosome-remodeling is largely unexplored. Recent studies show that the functional loss of BAF53b, a postmitotic neuron-specific subunit of the BAF nucleosome-remodeling complex, results in the deficit of consolidation of hippocampus-dependent memory and cocaine-associated memory in the rodent brain. However, it is unclear whether BAF53b expression is regulated during memory formation and how BAF53b regulates fear memory in the amygdala, a key brain site for fear memory encoding and storage. To address these questions, we used viral vector approaches to either decrease or increase BAF53b function specifically in the lateral amygdala of adult mice in auditory fear conditioning paradigm. Knockdown ofBaf53bbefore training disrupted long-term memory formation with no effect on short-term memory, basal synaptic transmission, and spine structures. We observed in our qPCR analysis that BAF53b was induced in the lateral amygdala neurons at the late consolidation phase after fear conditioning. Moreover, transient BAF53b overexpression led to persistently enhanced memory formation, which was accompanied by increase in thin-type spine density. Together, our results provide the evidence that BAF53b is induced after learning, and show that such increase of BAF53b level facilitates memory consolidation likely by regulating learning-related spine structural plasticity.SIGNIFICANCE STATEMENTRecent works in the rodent brain begin to link nucleosome remodeling-dependent epigenetic mechanism to memory consolidation. Here we show that BAF53b, an epigenetic factor involved in nucleosome remodeling, is induced in the lateral amygdala neurons at the late phase of consolidation after fear conditioning. Using specific gene knockdown or overexpression approaches, we identify the critical role of BAF53b in the lateral amygdala neurons for memory consolidation during long-term memory formation. Our results thus provide an idea about how nucleosome remodeling can be regulated during long-term memory formation and contributes to the permanent storage of associative fear memory in the lateral amygdala, which is relevant to fear and anxiety-related mental disorders.
authors.affiliation: Department of Biological Sciences, KAIST Institute for the BioCentury, Korea Advanced Institute of Science and Technology, Daejeon 34141, Korea.
authors.forename: Miran
authors.initials: M
authors.lastname: Yoo
authors.affiliation: Graduate School of Medical Science and Engineering, Korea Advanced Institute of Science and Technology, Daejeon 34141, Korea, and.
authors.forename: Kwang-Yeon
authors.identifier: 0000-0001-7134-8723
authors.initials: KY
authors.lastname: Choi
authors.affiliation: Department of Biological Sciences, KAIST Institute for the BioCentury, Korea Advanced Institute of Science and Technology, Daejeon 34141, Korea.
authors.forename: Jieun
authors.initials: J
authors.lastname: Kim
authors.affiliation: Department of Biological Sciences, KAIST Institute for the BioCentury, Korea Advanced Institute of Science and Technology, Daejeon 34141, Korea.
authors.forename: Mujun
authors.initials: M
authors.lastname: Kim
authors.affiliation: Department of Biological Sciences, College of Natural Sciences, Seoul National University, Seoul 08826, Korea.
authors.forename: Jaehoon
authors.initials: J
authors.lastname: Shim
authors.affiliation: Department of Biological Sciences, College of Natural Sciences, Seoul National University, Seoul 08826, Korea.
authors.forename: Jun-Hyeok
authors.initials: JH
authors.lastname: Choi
authors.affiliation: Department of Biological Sciences, KAIST Institute for the BioCentury, Korea Advanced Institute of Science and Technology, Daejeon 34141, Korea.
authors.forename: Hye-Yeon
authors.initials: HY
authors.lastname: Cho
authors.affiliation: Department of Biological Sciences, KAIST Institute for the BioCentury, Korea Advanced Institute of Science and Technology, Daejeon 34141, Korea.
authors.forename: Jung-Pyo
authors.initials: JP
authors.lastname: Oh
authors.affiliation: Department of Biological Sciences, KAIST Institute for the BioCentury, Korea Advanced Institute of Science and Technology, Daejeon 34141, Korea.
authors.forename: Hyung-Su
authors.identifier: 0000-0001-7749-1029
authors.initials: HS
authors.lastname: Kim
authors.affiliation: Department of Biological Sciences, College of Natural Sciences, Seoul National University, Seoul 08826, Korea.
authors.forename: Bong-Kiun
authors.identifier: 0000-0001-7593-9707
authors.initials: BK
authors.lastname: Kaang
authors.affiliation: Department of Biological Sciences, KAIST Institute for the BioCentury, Korea Advanced Institute of Science and Technology, Daejeon 34141, Korea, han.jinhee@kaist.ac.kr.
authors.forename: Jin-Hee
authors.initials: JH
authors.lastname: Han
mesh_terms: D000199:Actins / Q000378:metabolism*; D000679:Amygdala / Q000502:physiology*; D000818:Animals; D002868:Chromosomal Proteins, Non-Histone / Q000378:metabolism*; D004268:DNA-Binding Proteins / Q000378:metabolism*; D005239:Fear / Q000502:physiology*; D005260:Female; D008297:Male; D000069077:Memory Consolidation / Q000502:physiology*; D051379:Mice; D008810:Mice, Inbred C57BL; D018345:Mice, Knockout; D008822:Mice, Transgenic; D009473:Neuronal Plasticity / Q000502:physiology; D009474:Neurons / Q000378:metabolism*; D009707:Nucleosomes / Q000378:metabolism*
chemical_list: D000199:Actins; C485486:Actl6a protein, mouse; D002868:Chromosomal Proteins, Non-Histone; D004268:DNA-Binding Proteins; D009707:Nucleosomes
keywords: BAF53b; fear conditioning; long-term memory; memory consolidation; nucleosome remodeling; spine structural plasticity