Functional State of Developing Retinogeniculate Synapse

视网膜突触发育的功能状态

• 批准号: 6877664
• 负责人: WILLIAM GUIDO
• 金额: $ 31.4万
• 依托单位: LSU HEALTH SCIENCES CENTER
• 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 2008-11-30
• 项目状态: 已结题
• 来源: https://reporter.nih.gov/project-details/6877664
• 关键词: SDS polyacrylamide gel electrophoresis; calcium channel; developmental neurobiology; electrical potential; electrophysiology; electrostimulus; genetically modified animals; immunocytochemistry; infant animal; laboratory mouse; lateral geniculate body; long term potentiation; membrane potentials; neural plasticity; optic nerve; protein structure function; retinal ganglion; synapses; synaptogenesis; tissue /cell culture; visual deprivation; western blottings

DESCRIPTION (provided by applicant): Much of our present understanding regarding the activity-dependent refinement of sensory connections is based on work done in the developing retinogeniculate pathway. Despite the overwhelming evidence underscoring the role of activity in shaping the refinement of retinogeniculate connections, the cellular and molecular mechanisms underlying these processes remain a topic of intense inquiry. We have developed a rodent model of visual system development in which we characterized the structural and functional changes occurring in the lateral geniculate nucleus (LGN) during early postnatal life. Our experiments reveal that the changes in retinogeniculate axon patterning and connectivity are linked to Hebbian-like modifications in synaptic strength and the activation of L-type Ca2+ channels. However, the role of L-type Ca2+ channels and their expression during retinogeniculate development remain largely unexplored. The major goals of this project is to investigate the nature of L-type Ca2+ activity during early postnatal life and establish a direct link between such activity and the remodeling of retinogeniculate connections. We shall use electrophysiological, anatomical, and biochemical techniques to delineate the nature of L-type Ca2+ channel expression and its role in retinogeniculate development. We shall take advantage of transgenic mice lines in which L-type Ca2+ activity and channel expression has been severely attenuated by the targeted deletion of either the beta2 or beta3 subunit of the Ca2+ channel. These mice offer a unique opportunity to relate L-type Ca2+ function with synapse stabilization and activity dependent remodeling in LGN.

描述（由申请人提供）：我们目前对感官连接的参与性的完善的理解是基于在发育中的视网膜生成途径中所做的工作。尽管有大量的证据强调了活动在塑造视网膜化连接的完善中的作用，但这些过程的细胞和分子机制仍然是一个强烈的查询话题。我们已经开发了一种视觉系统发展的啮齿动物模型，其中我们表征了产后早期寿命期间横向元素核（LGN）发生的结构和功能变化。我们的实验表明，视视性轴突模式和连通性的变化与Hebbian样突触强度的修饰和L型Ca2+通道的激活有关。但是，L型Ca2+通道的作用及其在视网膜生成发育过程中的表达在很大程度上尚未得到探索。该项目的主要目标是研究产后早期生活期间L型Ca2+活性的性质，并在这种活动与视网膜生成联系的重塑之间建立直接联系。我们将使用电生理，解剖学和生化技术来描述L型Ca2+通道表达的性质及其在视网膜生成发育中的作用。我们将利用转基因小鼠管线，其中L型Ca2+活性和通道表达通过Ca2+通道的beta2或beta3亚基的靶向缺失严重减弱。这些小鼠提供了一个独特的机会，将L型Ca2+功能与突触稳定和LGN中的活性重塑相关联。