Plasticity of the Retinogeniculate Synapse

视网膜突触的可塑性

• 批准号: 10223312
• 负责人: Chinfei Chen
• 金额: $ 65.53万
• 依托单位: BOSTON CHILDREN'S HOSPITAL
• 依托单位国家: 美国
• 财政年份: 2003
• 资助国家: 美国
• 起止时间: 2003-09-01 至 2024-07-31
• 项目状态: 已结题
• 来源: https://reporter.nih.gov/project-details/10223312
• 关键词: Age; Amblyopia; Applications Grants; Axon; Birth; Brain; Cells; Color; Critical Pathways; Cues; Data; Development; Diffuse; Dorsal; Electrophysiology (science); Environment; Experimental Models; Exposure to; Eye; Feedback; Funding; Future; Genetic; Geniculate body structure; In Vitro; Laboratories; Lateral Geniculate Body; Logic; Maps; Mediating; Mental Retardation; Modeling; Molecular; Molecular Probes; Mus; Nervous System Physiology; Neurologic; Neurons; Pattern; Phase; Pilot Projects; Play; Population; Process; Property; Publishing; Retina; Retinal Ganglion Cells; Role; Sensory; Series; Shapes; Slice; Structure; Synapses; Synaptic plasticity; System; Systems Development; Testing; Thalamic structure; Time; Vision Disorders; Visual; Visual Pathways; Visual Perception; Visual system structure; Work; cell type; critical period; deprivation; design; developmental plasticity; experience; experimental study; in vivo; in vivo imaging; information processing; insight; loss of function; neural circuit; neuronal circuitry; optogenetics; orientation selectivity; postsynaptic; receptive field; recruit; response; retinal axon; retinogeniculate; sensory system; tool; visual deprivation

ABSTRACT The formation and refinement of synaptic circuits are fundamental to neurological function. To understand the basic mechanisms and logic of neuronal circuit refinement, the Chen Lab uses the mouse visual system as our experimental model. This model offers a simplified circuitry and genetic accessibility and control of different neurons along the visual pathway. We study the connection between retinal ganglion cells (RGCs) in the eye and relay neurons in the dorsolateral geniculate nucleus (dLGN, the visual thalamus) of mice, a synapse that shows robust synaptic plasticity during development. Our studies have revealed that synaptic plasticity at the retinogeniculate synapse extends much longer than previously recognized–long after eye-opening in mice. We also found that that during this late developmental period, retinothalamic circuits undergo a critical period of experience-dependent refinement, previously thought to be an exclusive feature of cortical circuits. Notably, sensory experience during a late window of development can rewire retinogeniculate connectivity, changing both the strength and number of afferent retinal inputs onto a given thalamocortical neuron. In the prior funding period we demonstrated that, during the thalamic critical period, changes in cortical activity can feedback to the thalamus to alter connectivity of subcortical circuits. Our work demonstrates that rather than developing sequentially–with circuits of the eye maturing before those of the thalamus and still later the cortex–interactions between these stations of the visual pathway are critical for proper neurologic development. Yet, the question persists: What is the purpose of the thalamic experience-dependent critical period? Results from a recent study from our laboratory provide hints of an answer to this question–– in a collaborative effort with the Andermann Laboratory, we visualized retinal axons in the dLGN and found that different information lines from the retina converging onto a thalamocortical neuron are matched to specific features of the visual space to efficiently transmit tuned information. We now propose to test the idea that the exquisite organization of the retinogeniculate synapse gives rise to feature selectivity in the dLGN, and that these features are fine-tuned by cortical feedback during the thalamic critical period. Using a combination of tools including dual-color optogenetics, chemogenetics, in vitro slice electrophysiology, and in vivo single unit recordings along with in vivo imaging of retinal axon boutons, we propose a series of experiments to test the hypothesis that experience-dependent plasticity at the retinogeniculate synapse drives the fine-tuning of select receptive field features that are sensitive to environmental cues.

摘要 突触回路的形成和完善是神经功能的基础。要了解 神经元回路精化的基本机制和逻辑，陈实验室使用小鼠视觉系统作为我们的 实验模型。该模型提供了简化的电路和遗传可及性以及对不同 视觉通路上的神经元。我们研究了眼睛中视网膜神经节细胞(RGC)之间的联系 和小鼠膝状体背外侧核(dLGN，视觉丘脑)中的中继神经元，这种突触 在发育过程中表现出强大的突触可塑性。我们的研究表明，突触的可塑性在 在小鼠睁开眼睛很久之后，视黄素原性突触延长的时间比以前认识的要长得多。我们 还发现，在这个发育后期，视网膜丘脑回路经历了一个关键期 依赖经验的精炼，以前被认为是大脑皮层回路的独有功能。值得注意的是， 在发育后期的感觉体验可以重新连接视网膜原细胞，改变 对给定丘脑皮质神经元的视网膜传入的强度和数量。在之前的资助中 我们证明，在丘脑的关键期，皮质活动的变化可以反馈到 丘脑改变皮质下环路的连通性。我们的工作表明，与其说发展 顺序地--眼睛的回路在丘脑的回路之前成熟，然后是皮质--相互作用 在视觉通路的这些站之间对正常的神经发育至关重要。然而，问题是 坚持：丘脑经验依赖关键期的目的是什么？最近一次调查的结果 我们实验室的研究为这个问题的答案提供了线索--与 Andermann实验室，我们对dLGN中的视网膜轴突进行了可视化，并发现来自 汇聚到丘脑皮质神经元上的视网膜与视觉空间的特定特征相匹配，以 高效地传输调谐信息。我们现在建议测试一下这样一个想法，即 视黄素原化突触在dLGN中引起特征选择性，并且这些特征由 丘脑关键期的皮质反馈。使用包括双色在内的多种工具组合 光遗传学、化学遗传学、体外切片电生理学、活体单单位记录以及In 对于视网膜轴突的活体成像，我们提出了一系列实验来验证这一假设 视网膜起源突触的经验依赖性可塑性驱动选择感受野的微调 对环境线索敏感的特征。