Functional State of Developing Retinogeniculate Synapse

视网膜突触发育的功能状态

• 批准号: 7286444
• 负责人: WILLIAM GUIDO
• 金额: $ 24.23万
• 依托单位: VIRGINIA COMMONWEALTH UNIVERSITY
• 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/7286444
• 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）：我们目前对感觉连接的活动依赖性改进的大部分理解是基于在发育中的视网膜原化通路中所做的工作。尽管有大量的证据强调活动在形成视网膜原化连接的完善过程中所起的作用，但这些过程背后的细胞和分子机制仍然是一个深入研究的话题。我们已经开发了一个啮齿动物的视觉系统的发展模型，我们表征结构和功能的变化发生在外侧膝状核（LGN）在出生后的早期生活。我们的实验表明，维甲酸轴突模式和连通性的变化与突触强度的hebbian样改变和l型Ca2+通道的激活有关。然而，l型Ca2+通道及其表达在视网膜新生发育中的作用在很大程度上仍未被探索。该项目的主要目标是研究出生后早期生活中l型Ca2+活性的性质，并建立这种活性与视网膜新生细胞连接重塑之间的直接联系。我们将使用电生理、解剖和生化技术来描述l型Ca2+通道表达的性质及其在视网膜新生发育中的作用。我们将利用转基因小鼠系，其中l型Ca2+活性和通道表达已被Ca2+通道的β 2或β a3亚基的靶向删除严重减弱。这些小鼠提供了一个独特的机会，将l型Ca2+功能与突触稳定和活动依赖性重构在LGN中联系起来。