FUNCTIONAL STATE OF DEVELOPING RETINOGENICULATE SYNAPSE

视网膜生成突触发育的功能状态

基本信息

批准号：
6287693
负责人：
WILLIAM GUIDO
金额：
$ 20.41万
依托单位：
LSU HEALTH SCIENCES CENTER
依托单位国家：
美国
项目类别：
财政年份：
2001
资助国家：
美国
起止时间：
2001-05-01 至 2004-04-30
项目状态：
已结题

来源：
https://reporter.nih.gov/project-details/6287693
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

项目摘要

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神经科学的目的是了解神经系统背后的细胞机制发展意义之间突触连接的建立和完善器官及其中心目标。在过去的二十年里，哺乳动物视网膜原化途径已成为展示如何形成精确的连接模式以及形成模式的方式活动塑造了他们。睁眼前，视网膜神经节聚集细胞以协调的时空方式放电。这些冲动传播到电波穿过视网膜，然后传输到 LGN 并导致中继细胞强烈放电。人们普遍认为，此类活动对于最终雕刻出类似成人的视网膜连接。而且，关联突触过程，例如长时程增强 (LTP) 和长期抑郁 (LTD) 被认为代表赫布底物维持哪些共同主动输入以及较少主动和/或异步输入被修剪。尽管有大量证据强调活动的作用在塑造视黄质连接的细化过程中，仍有待观察发育中的视网膜神经节的协调放电模式是否细胞可以支持突触强度的赫布修改。初级本提案的目标是确定内在的发育中的视网膜神经节细胞的活性可以支持长期的变化 LGN 中的突触功效（增强和抑制），然后确定这种联想变化是否是依赖于活动的细化的基础视网膜原代连接。研究 LGN 细胞的突触反应通过利用分离的脑干制剂，其中背侧丘脑和每个视神经的大部分都保持完整。使用体外记录技术，视神经受到电击，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。确定 LGN细胞的突触反应是否会受到长期影响修改，视神经通过重复电击受到电击视网膜纤维以模仿协调放电模式的方式视网膜神经节细胞或以模拟视网膜活动减少的方式。具体来说，我们计划测试联想过程是否像长期的视网膜原突触处存在增强或抑制，了解是否突触强度的变化与突触稳定性有关视网膜原代连接，并阐明其背后的药理学这种可塑性的诱导和维持。