FUNCTIONAL STATE OF DEVELOPING RETINOGENICULATE SYNAPSE

描述(改编自申请者的摘要)：一个重要而持久的问题 在神经科学中的作用就是了解 发育中感觉之间突触连接性的建立和完善 器官及其中心靶点。在过去的二十年里，哺乳动物 视黄素生成途径已经成为一个重要的模型来说明 形成了精确的连接性模式，并以模式的方式 活动塑造了他们。睁开眼睛前，视网膜神经节聚集体 细胞以一种协调的时空方式发射。这些冲动在 穿过视网膜的电波，然后被传递到LGN，并导致中继细胞 强烈地释放。人们普遍认为，这样的活动是必要的 成人型视网膜细胞连接的最终造型。此外， 联合突触过程，如长时程增强(LTP)和 长期抑郁(LTD)被认为是Hebbian底物的代表，通过 哪些协同输入被保持，哪些不那么活跃和/或异步 都被修剪掉了。尽管有压倒性的证据强调活动的作用 在塑造视网膜起源连接的精细化方面，它仍有待于 观察发育中视网膜神经节的协同放电模式 细胞可以在突触强度上支持Hebbian修饰。初级阶段 本提案的目标是确定是否存在内在的 发育中的视网膜神经节细胞的活动可以支持长期的变化 LGN的突触效应(增强和抑制)然后确定 这种关联变化是否构成依赖于活动的细化的基础 视网膜原基连接。LGN细胞突触反应的研究 通过利用分离的脑干制剂，背侧丘脑和 每条视神经的大部分都保持完好。使用体外记录 技术上，视神经受到电击，突触 IGN中的反应以全细胞内细胞内的形式记录 反应(EPSPS和EPSCs)或细胞外RILED电位。要确定 LGN细胞的突触反应是否受制于长时程 修改，视神经通过传递重复的电击 视网膜纤维的方式模仿了 视网膜神经节细胞或以某种方式模拟视网膜活动减少。 具体地说，我们计划测试联想过程是否喜欢长期 视黄素原性突触存在增强或抑制，了解 突触强度的变化与神经元的稳定有关 视黄素生成连接，并阐明潜在的药理学 这种可塑性的诱导和维持。

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.