DC Field | Value | Language |
---|---|---|
dc.contributor.advisor | Kim, Eun Joon | - |
dc.contributor.advisor | 김은준 | - |
dc.contributor.author | Lee, Hye jin | - |
dc.date.accessioned | 2019-08-22T02:43:31Z | - |
dc.date.available | 2019-08-22T02:43:31Z | - |
dc.date.issued | 2016 | - |
dc.identifier.uri | http://library.kaist.ac.kr/search/detail/view.do?bibCtrlNo=849814&flag=dissertation | en_US |
dc.identifier.uri | http://hdl.handle.net/10203/264774 | - |
dc.description | 학위논문(박사) - 한국과학기술원 : 생명과학과, 2016.2,[vii, 135 p. :] | - |
dc.description.abstract | Synaptic adhesion molecules are thought to contribute to the development, function, and plasticity of neuronal synapses largely through their trans-synaptic synaptic adhesions. I found here that NGL-3 (netrin-G ligand-3), a postsynaptic adhesion molecule that trans-synaptically interacts with the LAR family of receptor tyrosine phosphatases and intracellularly with the postsynaptic scaffolding protein PSD-95, undergoes a proteolytic cleavage process. NGL-3 cleavage is induced by NMDA treatment in cultured neurons or low frequency stimulation in brain slices, and requires the activities of NMDA glutamate receptors, matrix metalloproteinases (MMPs), and presenilin/$\gamma$-secretase. NGL-3 mutant (Ngl3$^{-/-}$ mice) mice show normal synaptic transmission, but impaired long term potentiation and depression. Behaviorally, Ngl3$^{-/-}$ mice showed hyperactivity, anxiolytic-like behaviors, and impaired learning and memory. Hyperactivity of Ngl3$^{-/-}$ mice is partially rescued by D-cycloserine, a partial NMDA receptor agonist, whereas anxiolytic-like behaviors are not. These results suggest that NGL-3 is a novel substrate of MMPs and $\gamma$-secretase and that NGL-3 cleavage may regulate synaptic adhesion during NMDA-dependent LTD. NGL-3 is important for normal brain development, synaptic plasticity, locomotion, anxiety-like behavior, and learning and memory in vivo. Lastly, these results suggest that reduced NMDA receptor activity may lead to hyperactivity in Ngl3$^{-/-}$ mice. | - |
dc.language | eng | - |
dc.publisher | 한국과학기술원 | - |
dc.subject | neuroscience▼asynapse▼aadhesion molecule▼aNGL-3▼acleavage | - |
dc.subject | 신경과학▼a시냅스▼a접착단백질▼a동물행동분석▼a절단 | - |
dc.title | Regulation of synapse development and function by the synaptic adhesion molecule NGL-3 | - |
dc.title.alternative | 시냅스 접착 단백질 NGL-3 에 의한 시냅스 발달과 기능 조절에 관한 연구 | - |
dc.type | Thesis(Ph.D) | - |
dc.identifier.CNRN | 325007 | - |
dc.description.department | 한국과학기술원 :생명과학과, | - |
dc.contributor.alternativeauthor | 이혜진 | - |
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