FUNCTIONAL STATE OF DEVELOPING RETINOGENICULATE SYNAPSE

视网膜生成突触发育的功能状态

• 批准号: 6682904
• 负责人: WILLIAM GUIDO
• 金额: $ 17.88万
• 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 2004-11-30
• 项目状态: 已结题
• 来源: https://reporter.nih.gov/project-details/6682904
• 关键词: calcium channel; developmental neurobiology; electrical potential; electrodes; electrophysiology; electrostimulus; intercellular connection; laboratory mouse; laboratory rat; lateral geniculate body; long term potentiation; neural plasticity; optic nerve; organ culture; retinal ganglion; synaptogenesis

DESCRIPTION (Adapted from applicant's abstract): A major and enduring question in neuroscience is to understand the cellular mechanisms underlying the establishment and refinement of synaptic connectivity between developing sense organs and their central targets. Over the past two decades, the mammalian retinogeniculate pathway has served as an important model for demonstrating how precise patterns of connectivity are formed and the manner in which patterned activity shapes them. Prior to eye opening, aggregates of retinal ganglion cells fire in a coordinated spatiotemporal manner. These impulses travel in waves across the retina, are then transmitted to LGN and cause relay cells to strongly discharge. It is widely believed that such activity is needed for the final sculpting of adult-like retinogeniculate connections. Moreover, associative synaptic processes such as long-term potentiation (LTP) and long-term depression (LTD) are thought to represent the Hebbian substrate by which co-active inputs are maintained and less active and/or asynchronous ones are pruned. Despite the overwhelming evidence underscoring the role of activity in shaping the refinement of retinogeniculate connections, it remains to be seen whether the coordinated discharge patterns of developing retinal ganglion cells can support Hebbian modifications in synaptic strength. The primary objectives of the present proposal are to ascertain whether the intrinsic activity of developing retinal ganglion cells can support long-term changes in synaptic efficacy (potentiation and depression) in LGN and then determine whether such associative changes underlie the activity-dependent refinement of retinogeniculate connections. The synaptic responses of LGN cells are studied by utilizing an isolated brainstem preparation where the dorsal thalamus and large segments of each optic nerve remain intact. Using in vitro recording techniques, the optic nerves are electrically shocked and the synaptic responses in IGN are recorded either in the form of whole-cell intracellular responses (EPSPs and EPSCs) or extracellular riled potentials. To determine whether the synaptic responses of LGN cells are subject to long-term modification, optic nerves are shocked by delivering repetitive shocks to retinal fibers in a manner that mimics the concerted discharge patterns of retinal ganglion cells or in a way that models reduced retinal activity. Specifically, we plan to test whether associative processes like long-term potentiation or depression exist at the retinogeniculate synapse, learn whether changes in synaptic strength are linked to the stabilization of retinogeniculate connections, and to elucidate the pharmacology underlying the induction and maintenance of such plasticity.

描述（改编自申请人的摘要）：一个主要且持久的问题 在神经科学中是了解该细胞机制 建立和完善突触连通性 器官及其中心目标。在过去的二十年中，哺乳动物 视网膜生成途径已成为证明如何 形成了精确的连通性模式和图案的方式 活动塑造它们。开眼界之前，视网膜神经节的聚集体 细胞以协调的时空方式发射。这些冲动旅行 然后将波浪跨过视网膜，然后传播到LGN，并导致继电器细胞到 强烈排出。人们普遍认为需要这样的活动 最终的成人视网膜生成连接的雕塑。而且， 长期增强（LTP）等关联突触过程和 长期抑郁（LTD）被认为代表Hebbian底物 维持哪些共同活性输入，较少的活动和/或异步 修剪。尽管有大量证据强调了活动的作用 在塑造视网膜生成的连接的完善时，它仍然是 查看是否开发视网膜神经节的配位排放模式 细胞可以支持Hebbian的突触强度修饰。主要 本提案的目标是确定固有的 发展视网膜神经节细胞的活性可以支持长期变化 LGN中的突触功效（增强和抑郁），然后确定 这种关联的变化是否依赖于活动依赖性的改进 视网膜生成的连接。研究了LGN细胞的突触反应 通过利用丘脑背丘脑和 每个视神经的大段保持完整。使用体外记录 技术，视神经被电击和突触 IGN中的响应以全细胞内的形式记录 反应（EPSP和EPSC）或细胞外腐烂的电势。确定 LGN细胞的突触反应是否长期进行 修改后，通过将重复性冲击传递到 视网膜纤维以模仿一致的放电模式的方式 视网膜神经节细胞或模型减少视网膜活性的方式。 具体而言，我们计划测试是否像长期这样的关联过程 视网膜生成突触中存在增强或抑郁症，了解是否存在 突触强度的变化与稳定有关 视网膜原理连接，并阐明了依据的药理学 这种可塑性的诱导和维护。