The Role of miRNA in Activity-Dependent Synaptic Plasticity- [electronic resource]
The Role of miRNA in Activity-Dependent Synaptic Plasticity- [electronic resource]
- 자료유형
- 학위논문파일 국외
- 최종처리일시
- 20240214100445
- ISBN
- 9798379612986
- DDC
- 616
- 서명/저자
- The Role of miRNA in Activity-Dependent Synaptic Plasticity - [electronic resource]
- 발행사항
- [S.l.]: : Harvard University., 2023
- 발행사항
- Ann Arbor : : ProQuest Dissertations & Theses,, 2023
- 형태사항
- 1 online resource(83 p.)
- 주기사항
- Source: Dissertations Abstracts International, Volume: 84-12, Section: B.
- 주기사항
- Advisor: Van Vactor, David.
- 학위논문주기
- Thesis (Ph.D.)--Harvard University, 2023.
- 사용제한주기
- This item must not be sold to any third party vendors.
- 초록/해제
- 요약During processes like learning and memory, neural activity dynamically remodels synaptic connectivity which is critical for adaptive behavior and memory storage. At the molecular level, regulatory control of transcription and translation are indispensable for this process. Accordingly, the neuron is equipped with a robust arsenal of regulatory sensors that tightly couple changes in neural activity with transcription and protein synthesis. Within this regulatory framework, individual mRNA translation can be terminally repressed or temporarily stalled by the action of microRNAs (miRNAs). miRNAs are deployed downstream of neural activity to mediate rapid modulation of protein synthesis locally within synaptic compartments. Such regulation is distinct from classic modes of transcriptional control that regulate gene expression on relatively broad spatial and temporal scales. In contrast, the regulatory action of miRNAs can be acutely triggered to regulate mRNA translation for rapid activity-dependent modulation of local synaptic structure. Here, we have used the Drosophila neuromuscular junction to broadly survey the regulatory contributions of human conserved miRNAs during structural plasticity of the synaptic terminal. Importantly, I have discovered miRNA-973 (miR-973) as a novel regulator of synaptic structure downstream of neural activity. Accordingly, loss of miR-973 function leads to an activity-dependent degeneration of synaptic boutons. In this context, bouton decay is marked by the unique accumulation of peri-synaptic membranous debris, which is consistent with degenerative phenotypes. Mechanistically, I have shown miR-973 regulates Down Syndrome Cell Adhesion Molecule 2 (DSCAM2), a known regulator of synaptic endocytosis and vesicular dynamics. Importantly, the synaptic degeneration phenotypes associated with miR-973 loss of function can be rescued by DSCAM2 inhibition, which underscores an important role for the miR-973-DSCAM2 regulatory interaction during plasticity of synaptic structure in an activity-dependent context.
- 일반주제명
- Neurosciences.
- 일반주제명
- Molecular biology.
- 일반주제명
- Genetics.
- 키워드
- MicroRNA
- 키워드
- Neural activity
- 키워드
- Neurobiology
- 키워드
- Neuroscience
- 키워드
- Synapse
- 기타저자
- Harvard University Medical Sciences
- 기본자료저록
- Dissertations Abstracts International. 84-12B.
- 기본자료저록
- Dissertation Abstract International
- 전자적 위치 및 접속
- 로그인 후 원문을 볼 수 있습니다.