DEVELOPMENT OF SYNAPTIC PATHWAYS IN RETINA

由视网膜处理的视觉场景的神经元图像 是兴奋和抑制之间复杂相互作用的结果 并通过视网膜神经节细胞（RGC）锋电位传导至大脑 活动在生命的早期，这种视觉诱发的活动会影响 外侧膝状体突触整合与视觉信号处理 核和视觉皮层。关于视网膜是否 神经元连接和突触活动也受到 视觉体验 这项拟议研究的目标之一是确定和量化 突触输入RGC和特征的作用，发展对 调节这些细胞的突触活动。为此， 自发和光诱发兴奋性和抑制性突触输入 的RGC将使用贴片电极记录技术从 视网膜切片制备。兴奋性和 将确定小鼠RGC中的抑制性突触活动。在 此外，兴奋性神经元和抑制性神经元的相互作用 递质对RGC突触活动的发育调节 将在野生型小鼠和两种类型的转基因小鼠中进行检查 （GAD 65-/-和mGluR 6-/-）。 另一个主要目标是确定视觉体验在 RGC突触活动的发展，并了解 视网膜中经验依赖性突触可塑性的机制。 光剥夺和正常饲养小鼠视网膜神经节细胞的突触传入 将被研究。时间进程、关键期和可逆性 光剥夺诱导的RGC突触活动的影响将是 表征了视觉体验和视觉体验之间的相互作用 神经递质对突触发育的调节作用也将 通过使用转基因小鼠来确定，在转基因小鼠中， 兴奋性和抑制性神经递质被改变。 这些研究的结果对我们如何看待 在婴儿期和儿童期影响视力的疾病。他们还 为神经递质相关的治疗药物如何 影响人类视觉系统的正常发育。

The neuronal image of the visual scene that is processed by the retina is the result of a complex interplay between excitation and inhibition and is conducted to the brain by retinal ganglion cell (RGC) spike activity. In early life, this visual-evoked activity affects the synaptic integration and visual signal processing in lateral geniculate nucleus and visual cortex. Little is known about whether retinal neuronal connections and synaptic activities are also regulated by visual experience. One of the goals in this proposed study is to identify and quantify the synaptic inputs to RGCs and characterize the roles of development on the regulation of synaptic activity of these cells. Toward this end the spontaneous and light-evoked excitatory and inhibitory synaptic inputs of RGCs will be studied using patch electrode recording techniques from retinal slice preparation. The developmental profiles of excitatory and inhibitory synaptic activities in mouse RGCs will be determined. In addition, the roles of interaction of excitatory and inhibitory neuron transmitters on the developmental regulation of RGC synaptic activity will be examined in wild type mice and two types of transgenic mice (GAD65-/- and mGluR6-/-). Another primary goal is to determine the roles of visual experience on the development of RGC synaptic activity and to understand the mechanisms of experience-dependent synaptic plasticity in the retina. The synaptic inputs of RGCs from light-deprived and normally reared mice will be studied. The time course, critical period and reversibility of light deprivation-induced effects of RGC synaptic activity will be characterized. The roles of interactions between visual experience and neurotransmitters on the developmental regulation of synaptic will also be determined by using the transgenic mice in which the release of excitatory and inhibitory neurotransmitters is altered. The results of these studies have important implications in how we view pathologies that affect vision during infancy and childhood. They also provide insights to how neurotransmitter-related therapeutic drugs could affect normal development of the human visual system.