(The) role of BAF chromatin remodeling complex in long-term fear memmory formation = 공포 장기기억 형성에서 BAF 크로마틴 리모델링 복합체의 기능 연구

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Epigenetic regulation of gene expression has been implicated in long-lasting memory formation. However, little is known about the role of chromatin remodeling mechanism in learning and memory. Recent study reports that BAF53b, a post-mitotic neuron-specific subunit of Brg/Brm-associated factor (BAF) chromatin remodeling complex is involved in hippocampus-dependent memory formation. However, whether BAF53b plays a role for long-term fear memory formation in lateral amygdala (LA), and its underlying mechanisms remain unknown. To address these issues, I used viral vectors to manipulate expression level of BAF53b specifically in LA and investigated its effects on long-term memory formation and synaptic structural plasticity using auditory fear conditioning paradigm. First, I found that Baf53b knockdown in LA neurons impaired long-term, but not short-term, fear memory formation, proving that BAF53b function in LA is essential for long-term fear memory formation. Second, transient BAF53b overexpression in LA enhanced long-term memory up to one month with no effect on short-term memory. Third, at the synapse level, confocal imaging of synaptic spines, visualized with GFP or dye injection in LA after fear learning revealed that the density of thin-type spine was specifically increased in BAF53b-overexpressing neurons one hr after learning, while head volume of mushroom-type spine in BAF53b knockdown neurons was significantly decreased compared to that in control neurons 24 hrs after learning. In parallel to this result, RT-PCR analysis showed that Baf53b knockdown blocked activity-dependent upregulation of miR132, which is known to be involved in regulation of activity-dependent spine enlargement. Taken together, my results demonstrate that BAF53b in LA is essential for long-term fear memory formation of auditory fear conditioning and reveal novel underlying mechanisms of BAF53b during long-lasting memory formation.
Advisors
Han, Jin-Heeresearcher한진희researcher
Description
한국과학기술원 :의과학대학원,
Publisher
한국과학기술원
Issue Date
2015
Identifier
325007
Language
eng
Description

학위논문(박사) - 한국과학기술원 : 의과학대학원, 2015.8,[vi, 79 p. :]

Keywords

BAF53b; epigenetic; nBAF; structural plasticity; miR132; 구조적 가소성; 후성유전

URI
http://hdl.handle.net/10203/241970
Link
http://library.kaist.ac.kr/search/detail/view.do?bibCtrlNo=669255&flag=dissertation
Appears in Collection
MSE-Theses_Ph.D.(박사논문)
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