Activity-dependent Plasticity of Retinotectal Synapses

描述（申请人提供）：活动依赖性突触可塑性 在改善神经连接中起着重要作用， 神经系统的发育。该提案旨在进一步阐明 这一过程通过确定活动引起的 突触强度的变化，即长时程增强（LTP）和长时程增强（LTP）。 抑郁症（LTD）和连接的结构修改。尽管还很 已经了解了突触的功能可塑性（如LTP和LTD） 以及发育过程中连接的结构重塑， 他们之间的关系并不明确。我建议检查因果关系 突触强度变化与结构重塑的关系 发育中的爪蟾视网膜顶盖系统在该体内系统中，持续 突触强度的变化（LTP/LTD）可以由电或 视觉刺激和形态学的变化可以通过 双光子显微镜诱导后观察到结构变化， 海马中的LTP，反映为棘密度增加， 运动，丝状伪足的生长和新的棘和突触的形成， 穿孔的突触后致密物。此外，LTP的表达可以是 被干扰细胞骨架功能的药物部分阻断。 然而，仍有一些问题有待回答： LTP观察到的结构也发生在体内正常发育过程中？是 长期维持LTP所需的结构变化？可以 LTD的诱导引起结构变化，可能是在相反的方向， 由LTP引起的？我将使用同时在体内 非洲爪蟾视网膜顶盖系统的斑片记录和双光子成像。

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.