Activity-dependent Plasticity of Retinotectal Synapses

描述（由申请人提供）：活动依赖性突触可塑性 在神经连接的细化过程中起着重要作用 神经系统的发育。该提案旨在进一步阐明 这个过程通过确定活动诱发之间的因果关系 突触强度的变化，即长时程增强（LTP）和长时程增强 凹陷（LTD），以及连接的结构修改。虽然很多 已经了解了突触的功能可塑性（例如LTP和LTD） 以及开发过程中连接的结构重塑，关系 他们之间尚未明确确定。我建议检查一下因果关系 突触强度变化与结构重塑之间的关系 正在发育的非洲爪蟾视网膜顶盖系统。在这个体内系统中，持久 突触强度（LTP/LTD）的变化可以通过电或 视觉刺激和形态变化可以通过以下方式轻松检查 双光子显微镜。诱导后观察到结构变化 海马体中的 LTP，表现为棘密度增加和 运动性、丝状伪足的生长以及新棘和突触的形成 穿孔的突触后密度。此外，LTP 的表达可以 被干扰细胞骨架功能的药物部分阻断。 然而，还有一些问题需要回答： 用 LTP 观察到的结构在正常发育过程中也会出现在体内吗？是 长期维持 LTP 所需的结构变化？可以 LTD 的诱导导致结构变化，也许与 那些是由LTP引起的？我将使用体内同步技术来解决这些问题 爪蟾视网膜顶盖系统中的斑块记录和双光子成像。

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.