FUNCTIONAL STATE OF DEVELOPING RETINOGENICULATE SYNAPSE

描述（改编自申请人的摘要）：一个主要和持久的问题 神经科学中的一个重要任务是了解 发育中感觉之间突触连接的建立和完善 器官及其主要目标。在过去的二十年里， retinogeniculate途径作为一个重要的模型，说明如何 形成精确的连接图案， 活动塑造他们。在睁眼之前，视网膜神经节聚集 细胞以协调的时空方式放电。这些冲动在 穿过视网膜的波，然后被传输到LGN，并引起中继细胞， 强烈放电。人们普遍认为，这种活动是必要的， 最后形成成人状的视网膜膝状体连接。此外，委员会认为， 联合突触过程，如长时程增强（LTP）和 长期抑郁症（LTD）被认为是代表赫布基板， 哪些共同活动的输入被维持，哪些不太活动和/或异步 被修剪了。尽管有压倒性的证据强调活动的作用， 在形成视网膜膝状体连接的完善方面， 观察发育中的视网膜神经节的协调放电模式 细胞可以支持突触强度的Hebbian修饰。主 本建议的目的是确定是否固有的 发育中的视网膜神经节细胞的活性可以支持视网膜神经节细胞的长期变化。 LGN中的突触功效（增强和抑制），然后确定 这种关联性变化是否是依赖于活动的细化的基础， retinogeniculate连接.研究了LGN细胞的突触反应 通过利用分离的脑干制备，其中背侧丘脑和 每根视神经的大段都保持完整。使用体外记录 技术，视神经被电击，突触 IGN中的反应以全细胞细胞内的形式记录， 反应（EPSP和EPSC）或细胞外激发电位。以确定 LGN细胞的突触反应是否受到长期的 修改，视神经通过提供重复的电击来电击， 视网膜纤维的方式，模仿一致的放电模式， 视网膜神经节细胞或以模拟减少的视网膜活动的方式。 具体来说，我们计划测试是否像长期的关联过程， 增强或抑制存在于retinogeniculate突触，了解是否 突触强度的变化与突触的稳定性有关， retinogeniculate连接，并阐明药理学的基础， 诱导和维持这种可塑性。

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.