Functional state of developing retinogeniculate synapse

视网膜突触发育的功能状态

• 批准号: 8541664
• 负责人: WILLIAM GUIDO
• 金额: $ 11.55万
• 依托单位: UNIVERSITY OF LOUISVILLE
• 依托单位国家: 美国
• 财政年份: 2001
• 资助国家: 美国
• 起止时间: 2001-05-01 至 2012-11-30
• 项目状态: 已结题
• 来源: https://reporter.nih.gov/project-details/8541664
• 关键词: 3-Dimensional; Affect; Age; Attenuated; Axon; Biochemical; Biological Models; Brain; CREB1 gene; Cell Maturation; Cells; Cholera Toxin; Dendrites; Development; Dorsal; Elements; Event; Eye; Fiber; Figs - dietary; Goals; Growth; Health; In Vitro; Label; Lateral Geniculate Body; Lead; Length; Life; Link; Location; Maintenance; Mediating; Molecular; Morphology; Mus; Nature; Neurons; Pathway interactions; Pattern; Phase; Pigments; Play; Preparation; Prevalence; Process; Property; Retinal; Retinal Ganglion Cells; Role; Signal Transduction; Slice; Staging; Structure; Surgical sutures; Synapses; Synaptic plasticity; Techniques; Testing; Thalamic structure; Tissues; Tracer; Transgenic Mice; Visual; Western Blotting; attenuation; biocytin; developmental disease; developmental plasticity; experience; insight; membrane assembly; monocular; monocular deprivation; mouse model; nervous system disorder; postnatal; postsynaptic; reconstruction; relating to nervous system; research study; retinal axon; retinal stimulation; retinogeniculate; segregation; transcription factor; vision development

Description (provided by applicant): We have developed a mouse model of visual system development which characterizes the structural and functional changes occurring between retinal ganglion cell axons and their postsynaptic targets in the lateral geniculate nucleus (LGN) of thalamus. While many of the changes in retinogeniculate axon patterning and connectivity have been described, a number of issues remain unresolved. For example we know little about the neural elements and intracellular signaling cascades that govern why certain retinal inputs are preserved and strengthened while others are weakened and eventually eliminated. While many of the inductive changes in connectivity rely on a spontaneous retinal activity and a Hebbian form of synaptic plasticity, the role of visually evoked activity and the synaptic plasticity associated with the maintenance of newly remodeled connections has not been fully explored. Detailed morphological information about the growth and maturation of retinogeniculate synapses and the dendrites of LGN relay cells is also needed to fully appreciate how the remodeling of retinal connections occurs. The major goals of this renewal are: to use electrophysiological, anatomical, and biochemical techniques to detail the nature of L-type Ca2+ channel activity an event that appears essential for mediating activity dependent plasticity in LGN; to establish a link between L-type activity and the remodeling of retinogeniculate connections; to explore how alterations in visually evoked activity affect the maintenance of newly remodeled retinogeniculate connections; and to examine the dendritic morphology of developing LGN cells and determine how their structure-function relations are coordinated with the remodeling of retinal axons. Studies are done in wild-type pigmented mice as well as those in which L-type Ca2+ channel expression and activity has been severely attenuated by the targeted deletion of the 23 subunit. The developing retinogeniculate pathway in the mouse has emerged as a powerful model system to study the mechanisms underlying the remodeling of synaptic connections. Therefore, these studies will provide valuable information about how the developing brain forms precise patterns of connections and offer further insight into the study and treatment of developmental and neurological disorders that result from the formation of abnormal patterns of connectivity. PUBLIC HEALTH RELEVANCE: These studies will provide valuable information about how the developing brain forms precise patterns of connections and offer further insight into the study and treatment of developmental and neurological disorders that result from the formation of abnormal patterns of connectivity.

描述（由申请人提供）：我们开发了视觉系统发育的小鼠模型，其表征了视网膜神经节细胞轴突与其丘脑外侧膝状核（LGN）中的突触后目标之间发生的结构和功能变化。虽然视网膜原代轴突模式和连接性的许多变化已经被描述，但许多问题仍未解决。例如，我们对神经元件和细胞内信号级联知之甚少，这些神经元件和细胞内信号级联决定了为什么某些视网膜输入得以保留和增强，而另一些则被削弱并最终消除。虽然连接的许多诱导变化依赖于自发的视网膜活动和赫布形式的突触可塑性，但视觉诱发的活动和与维持新重塑的连接相关的突触可塑性的作用尚未得到充分探索。还需要有关视网膜原突触和 LGN 中继细胞树突的生长和成熟的详细形态学信息，以充分了解视网膜连接的重塑是如何发生的。此次更新的主要目标是：使用电生理学、解剖学和生化技术来详细说明 L 型 Ca2+ 通道活性的性质，该事件对于介导 LGN 中活性依赖性可塑性至关重要；建立L型活性与视网膜原连接重塑之间的联系；探索视觉诱发活动的改变如何影响新重塑的视网膜连接的维持；并检查发育中 LGN 细胞的树突形态，并确定它们的结构-功能关系如何与视网膜轴突的重塑相协调。研究在野生型色素小鼠以及 L 型 Ca2+ 通道表达和活性因 23 亚基的靶向删除而严重减弱的小鼠中进行。小鼠中正在发育的视网膜原化通路已成为研究突触连接重塑机制的强大模型系统。因此，这些研究将提供有关发育中的大脑如何形成精确的连接模式的宝贵信息，并为研究和治疗因异常连接模式而导致的发育和神经系统疾病提供进一步的见解。公共健康相关性：这些研究将提供有关发育中的大脑如何形成精确的连接模式的宝贵信息，并为研究和治疗因异常连接模式而导致的发育和神经系统疾病提供进一步的见解。