Development and Plasticity of a Retinotectal System

描述（由申请人提供）：在发育中的视觉系统中，视觉输入的时空模式在形成发育中的回路的连接中起重要作用。使用正在发展的非洲爪蟾蝌蚪视网膜顶盖系统和在体内全细胞记录和光学成像技术相结合，我们提出了检查的发展和经验依赖的细化视觉电路在细胞水平上。特别是，我们将研究活动依赖性持久性突触修饰（称为长时程增强/抑制（LTP/LTD））和视觉电路的发育完善之间的潜在联系。该建议包括四个部分。在第一部分中，我们将研究在顶盖突触发生的时间过程中，突触功能和可塑性的发育变化，并在顶盖神经元的感受野特性，使用全细胞记录方法，允许选择性评估的变化，在aphamatergic和GABA能/甘氨酸能输入到顶盖神经元。还将研究GABA能/甘氨酸能输入对感受野特性发育的调节影响。在第二部分中，我们将研究视觉经验诱发的活动对视网膜顶盖突触的影响，以及对视网膜定位图和感受野特性的影响。我们还将确定的作用，尖峰定时依赖可塑性的活动诱导的细化retinotectal连接。在第三部分中，我们将研究活动诱导的LTP/LTD和结构细化之间的关系，在确定的retinotectal连接和合作和竞争的相互作用之间的作用，会聚视网膜输入的树突上的单个顶盖神经元。最后，在第四部分，我们将研究的过程中，视觉输入诱导的LTP/LTD和结构修改的retinotectal连接可以巩固，并成为抵抗随后的自发尖峰活动在retinotectal系统的中断。两者合计，这些在体内的研究提供了独特的机会，以解决几个基本问题的指导性功能的感官输入在完善发展中的神经连接，并可能产生新的信息，我们的基本理解的生理和病理的发展中的神经系统。

DESCRIPTION (provided by applicant): In the developing visual system, the spatiotemporal patterns of visual inputs play an important role in shaping the connections of developing circuits. Using the developing retinotectal system of Xenopus tadpoles and a combination of in vivo whole cell recording and optical imaging techniques, we proposed to examine the development and experience-dependent refinement of visual circuits at the cellular level. In particular, we will examine the potential link between activity-dependent persistent synaptic modifications known as long-term potentiation/depression (LTP/LTD) and developmental refinement of visual circuits. The proposal consists of four parts. In PART I, we will examine the time course of synaptogenesis in the tectum, developmental changes in the synaptic function and plasticity and in the receptive field properties of tectal neurons, using a whole-cell recording method that allows the selective assessment of changes in glutamatergic and GABAergic/glycinergic inputs to the tectal neuron. The modulatory influence of GABAergic/glycinergic inputs on the development of receptive field properties will also be studied. In PART II, we will examine the effects of visual experience-evoked activity on retinotectal synapses and on the development of retinotopic map and receptive field properties. We will also determine the role of spike-timing dependent plasticity in the activity-induced refinement of retinotectal connections. In PART III, we will examine the relationship between activity-induced LTP/LTD and the structural refinement at identified retinotectal connections and the role of cooperative and competitive interactions among converging retinal inputs on the dendrite of single tectal neurons. Finally, in PART IV, we will examine the process by which visual input-induced LTP/LTD and structural modifications of retinotectal connections can be consolidated and become resistant to disruption by subsequent spontaneous spiking activity in the retinotectal system. Taken together, these in vivo studies provide unique opportunities to address several fundamental issues concerning the instructive function of sensory inputs in the refinement of developing neural connections, and are likely to yield new information relevant to our basic understanding of physiology and pathology of the developing nervous system.