Activity-dependent Plasticity of Retinotectal Synapses

视网膜顶盖突触的活动依赖性可塑性

• 批准号: 6784202
• 负责人: QIANG ZHOU
• 金额: $ 4.99万
• 依托单位: UNIVERSITY OF CALIFORNIA BERKELEY
• 依托单位国家: 美国
• 财政年份: 2002
• 资助国家: 美国
• 起止时间: 2002-08-01 至
• 项目状态: 未结题
• 来源: https://reporter.nih.gov/project-details/6784202
• 关键词: Xenopus; developmental neurobiology; long term potentiation; neural plasticity; neuroanatomy; neurophysiology; postdoctoral investigator; synapses; voltage /patch clamp

DESCRIPTION (provided by applicant): Activity-dependent synaptic plasticity plays an important role in the refinement of nerve connections during development of the nervous system. This proposal aims to shed more light on this process by determining the causal relationship between activity-induced changes in synaptic strength, namely long-term potentiation (LTP) and long-term depression (LTD), and structural modification of the connections. Though much has been learned about functional plasticity of synapses (such as LTP and LTD) and structural remodeling of connections during development, the relationship between them has not been clearly determined. I propose to examine the causal relationship between changes in synaptic strength and structural remodeling in the developing Xenopus retinotectal system. In this in vivo system, persistent changes in synaptic strength (LTP/LTD) can be induced by either electrical or visual stimulation and changes in morphology can be readily examined by two-photon microscopy. Structural changes have been observed after induction of LTP in the hippocampus, which is reflected as increased spine density and motility, growth of filopodia and formation of new spines and synapses with perforated post-synaptic densities. In addition, expression of LTP can be partially blocked by drugs interfering with the function of cytoskeleton. However, there are a few questions remaining to be answered: Do changes in structure observed with LTP also occur in vivo during normal development? Are changes in structure necessary for the long-term maintenance of LTP? Can induction of LTD cause structural changes, perhaps in the opposite direction of those caused by LTP? I will address these questions using simultaneous in vivo patch recording and two-photon imaging in Xenopus retinotectal system.

描述(申请人提供)：活性依赖的突触可塑性 在神经连接的精细化方面起着重要作用 神经系统的发育。这项提案旨在更多地阐明 这一过程通过确定活动诱导的因果关系 突触强度的变化，即长时程增强(LTP)和长时程 凹陷(LTD)，以及连接的结构修改。虽然很多 已了解突触的功能可塑性(如LTP和LTD) 和结构重塑在发展过程中的联系，关系 他们之间的关系还没有明确确定。我建议研究一下因果关系。 大鼠突触强度变化与结构重塑的关系 发育中的非洲爪哇视网膜顶盖系统。在这个体内系统中，持久化 突触强度的改变(LTP/LTD)可由电或 视觉刺激和形态变化可以很容易地通过 双光子显微镜。诱导后观察到结构的变化。 海马区的LTP，反映为脊柱密度增加和 丝状伪足的运动、生长和新棘突和突触的形成 突触后密度穿孔。此外，LTP表达可以是 被干扰细胞骨架功能的药物部分阻断。 然而，仍有几个问题有待回答：在 LTP观察到的结构在体内正常发育过程中也存在吗？是 长期维护LTP所需的结构变化？能 LTD的引入会导致结构变化，可能与 是由LTP引起的吗？我将使用体内同步来解决这些问题 非洲爪哇视网膜顶盖系统的斑片记录和双光子成像。