Plasticity of the Retinogeniculate Synapse

 描述(由申请人提供)：感觉系统的正确形成，如视觉系统，需要依赖经验的改进。传统上，人们认为感觉依赖的可塑性仅限于皮质，只有在皮质下通路稳定后才开始。然而，包括我们在内的许多实验室最近的研究表明，依赖经验的可塑性也发生在大脑皮层回路之外。陈实验室的研究表明，视网膜原性突触(视网膜神经节细胞(RGC)和丘脑中继神经元之间的连接)的精细化远远超出了早期发育，并包括一个关键期，在此期间突触前和突触后的伙伴可以视觉依赖的方式改变。丘脑晚期功能可塑性的发现代表着我们对传感器系统发展的理解发生了重大转变，因为它意味着皮质下回路与大脑皮质同时发生的经验重新连接。此外，就在这一关键期开始之前，大脑皮质存在广泛的反馈投射，支配丘脑，这表明，与感觉通路的顺序前馈发展模式不同，皮质下结构实际上可能包含来自皮质的反馈，以适当地成熟。事实上，我们在这里提供了支持这一假设的强有力的初步数据。在这项建议中，我们概述了实验，以进一步探索经验依赖性丘脑可塑性的目的和机制，以及皮质对这一过程的贡献。我们将利用光遗传和药物遗传工具在整个开发过程中操纵和表征特定的电路元件。

 DESCRIPTION (provided by applicant): The proper formation of sensory systems, such as the visual system, requires experience-dependent refinement. Traditionally, it was believed that sensory-dependent plasticity was limited to cortex and began only after subcortical pathways had stabilized. However recent studies from many laboratories, including ours, have demonstrated that experience-dependent plasticity also occurs outside of cortical circuits. Studies from the Chen laboratory have revealed that refinement of the retinogeniculate synapse, the connection between retinal ganglion cells (RGCs) and thalamic relay neurons, continues far beyond early development and includes a critical period during which pre- and post-synaptic partners can change in a vision-dependent manner. The discovery of late-stage functional plasticity in the thalamus represents a significant shift in our understanding of sensor system development, as it implies that subcortical circuits rewire with experience concurrently with cortex. Furthermore, the presence of extensive feedback projections from cortex that innervate thalamus just prior to the onset of this critical period suggests that, in contrast to th model of sequential, feedforward development of sensory pathways, subcortical structures may actually incorporate feedback from cortex to mature properly. Indeed, here we present strong preliminary data supporting this hypothesis. In this proposal, we outline experiments to further explore the purpose and mechanisms of experience-dependent thalamic plasticity, as well as the cortical contributions to this process. We will take advantage of optogenetic and pharmacogenetic tools to manipulate and characterize specific circuit components throughout development.