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ROLES OF NEUROTROPHINS IN OCULAR DOMINANCE PLASTICITY

神经营养因子在眼优势可塑性中的作用

基本信息

批准号：
6518618
负责人：
TAKUJI KASAMATSU
金额：
$ 28.39万
依托单位：
SMITH-KETTLEWELL EYE RESEARCH INSTITUTE
依托单位国家：
美国
项目类别：
财政年份：
2000
资助国家：
美国
起止时间：
2000-05-01 至 2005-04-30
项目状态：
已结题

来源：
https://reporter.nih.gov/project-details/6518618
关键词：
afferent nerve binocular vision cats immunocytochemistry nerve growth factors neural plasticity neural transmission neurophysiology neurotrophic factors single cell analysis statistics /biometry stereotaxic techniques synapses visual cortex visual stimulus

项目摘要

DESCRIPTION (Adapted from applicant's abstract): Neurotrophins (NTs) comprise a family of macromolecules that play a trophic support role in the developing cortex. They are also involved in activity-dependent processes in the adult cortex. In the proposed physiological experiments, we will determine whether NT's play a role in the regulation of ocular dominance plasticity in developing visual cortex. There are basically two possible outcomes of cortically infused NTs on developing binocular interactions: one is the suppression of binocular competition and the other its promotion. The two predictions come from two opposing views on the in vivo cellular action of endogenous NTs in the brain. In model 1, NTs are generally necessary for competing, especially immature, axon terminals to survive (survival factor" in Maffei's proposal). In model 2, NTs have a more specific role as a stabilizer of active synapses and whose release in controlled by afferent activity itself ("specific retrograde messenger" in Thoenen's hypothesis). In the proposed study, 6 physiological experiments are designed to maximally distinguish between the two models. Exp 1: Either nerve growth factor (NGF) or brain-derived neurotrophic factor (BDNF) will be directly infused into the kitten visual cortex for a week, concurrently with monocular lid suture. Changes in the ocular dominance distribution, in favor of model 1 or 2 or neither, will be compared between different concentrations of the two NTs. Exp 2: Each of the two NTs will be infused as Exp 1, but the eyes will be untouched to study effects of the competition on a natural level. This will allow examination of the direct chemical action of NTs on cortical activity. Exp 3: As a control for Exp 2, NT-infused, otherwise normal kittens will be kept in the dark during the week of the NT infusion. Exp 4: The effects of NT infusion will be studied in relation to an unusual level of binocular interactions between the tetrodotoxin-injected eye and the lid-sutured fellow eye. Exp 5: NTs will be infused into visual cortex of binocularly deprived kittens. The last two preparations are included because the discrimination between the above-mentioned two models is strong or moderated, if the specific effects of NTs are detectable. Exp 6: We will study whether rapid physiological effects of NTs shown in other in vivo systems also work to induce changes in ocular dominance under general anesthesia and paralysis. Exp 7: We will examine the intracortical spread of directly infused BDNF for a week or less. Using the "in vivo dilution curve" thus obtained, we will titrate the lowest-yet-effective concentrations of BDNF for its physiological effects.

描述（改编自申请人的摘要）：神经营养素（NT）包含在发育过程中发挥营养支持作用的大分子家族皮质。它们还参与成人的活动依赖过程皮质。在提议的生理实验中，我们将确定是否 NT 在发育过程中眼部优势可塑性的调节中发挥作用视觉皮层。皮质注入基本上有两种可能的结果 NT对发展双眼相互作用的作用：一是抑制双眼竞争，其二是其推广。这两个预测来自两个关于大脑内源性 NT 的体内细胞作用存在相反的观点。在模型1中，NT通常是竞争所必需的，尤其是不成熟的，轴突末梢生存（Maffei 提议中的“生存因素”）。在模型 2 中， NT 作为活跃突触的稳定剂具有更具体的作用，其释放由传入活动本身控制（“特定逆行 Thoenen 假设中的信使）。在拟议的研究中，6 个生理学实验旨在最大限度地区分这两个模型。经验值 1：神经生长因子（NGF）或脑源性神经营养因子（BDNF）将直接注入小猫视觉皮层一周，同时用单眼睑缝合。眼优势分布的变化模型 1 或模型 2 的偏好或两者都不偏好，将在不同的模型之间进行比较两种 NT 的浓度。实验 2：两个 NT 中的每一个都将被注入为实验 1，但眼睛不会被触及来研究竞争对实验的影响自然水平。这将允许检查 NT 的直接化学作用关于皮质活动。实验 3：作为实验 2 的对照，注入 NT，否则正常小猫在 NT 输注期间将被置于黑暗中。实验 4：NT 输注的效果将根据异常情况进行研究注射河豚毒素的眼睛和眼睛之间的双眼相互作用水平眼睑缝合的另一只眼睛。实验 5：NT 将被注入视觉皮层双眼被剥夺的小猫。包括最后两项准备工作是因为上述两种模型之间的区分度较强或如果 NT 的具体作用是可检测到的，则可以调节。实验6：我们将学习 NTs 的快速生理效应是否也显示在其他体内系统中致力于在全身麻醉下诱导眼优势的变化，麻痹。实验 7：我们将检查直接输注的皮质内扩散 BDNF 持续一周或更短时间。利用由此获得的“体内稀释曲线”，我们将滴定最低但有效的 BDNF 浓度生理效应。