Development and Plasticity of a Retinotectal System

描述(申请人提供)：在发育的视觉系统中，视觉输入的时空模式在形成发育中的回路的连接方面起着重要的作用。利用非洲爪哇蝌蚪发育中的视网膜顶盖系统，结合活体全细胞记录和光学成像技术，我们建议在细胞水平上研究视觉回路的发育和经验依赖性的细化。特别是，我们将研究被称为长时程增强/抑制(LTP/LTD)的活动依赖的持续性突触修饰(LTP/LTD)与视觉回路发育完善之间的潜在联系。该提案由四个部分组成。在第一部分中，我们将使用全细胞记录方法，研究顶盖突触发生的时间进程，突触功能和可塑性的发育变化，以及顶盖神经元感受野特性的变化，这种方法允许选择性地评估顶盖神经元的谷氨酸和GABA能/甘氨酸能输入的变化。还将研究GABA能/甘氨酸能输入对感受野特性发展的调制影响。在第二部分，我们将研究视觉体验诱发活动对视网膜顶盖突触的影响，以及对视网膜定位图和接受野特性的发展的影响。我们还将确定棘波时序依赖的可塑性在活动诱导的视网膜顶盖连接精细化中的作用。在第三部分中，我们将研究活动诱导的LTP/LTD与已识别的视网膜顶盖连接的结构优化之间的关系，以及单个顶盖神经元树突上汇聚的视网膜输入之间的合作和竞争相互作用的作用。最后，在第四部分中，我们将研究视觉输入诱导的LTP/LTD和视网膜顶盖连接的结构修改可以被巩固并变得对随后的视网膜顶盖系统中的自发尖峰活动的破坏产生抵抗的过程。综上所述，这些体内研究提供了独特的机会来解决几个基本问题，这些问题涉及到感觉输入在完善发育中的神经连接中的指导作用，并可能产生与我们对发育中的神经系统的生理学和病理学的基本理解相关的新信息。

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.