ROLES OF NEUROTROPHINS IN OCULAR DOMINANCE PLASTICITY

神经营养因子在眼优势可塑性中的作用

• 批准号: 6384783
• 负责人: TAKUJI KASAMATSU
• 金额: $ 27.97万
• 依托单位: SMITH-KETTLEWELL EYE RESEARCH INSTITUTE
• 依托单位国家: 美国
• 财政年份: 2000
• 资助国家: 美国
• 起止时间: 2000-05-01 至 2003-04-30
• 项目状态: 已结题
• 来源: https://reporter.nih.gov/project-details/6384783
• 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

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）：神经营养蛋白（NT）包含一个 在发育中起营养支持作用的大分子家族 皮层它们也参与成人的活动依赖性过程， 皮层在拟议的生理实验中，我们将确定是否 NT在发育过程中眼优势可塑性的调节中发挥作用 视觉皮层大脑皮层灌注的结果基本上有两种可能 NTs对发展双眼互动的影响：一是抑制双眼互动， 一个是竞争，另一个是提升。这两个预测来自两个 关于内源性NT在脑中的体内细胞作用的相反观点。 在模型1中，NTs通常是竞争所必需的，特别是不成熟的， 轴突终末存活（Maffei提出的“存活因子”）。 在模型2中， NT作为活跃突触的稳定剂具有更特定的作用， 由传入活动本身控制的释放（“特异性逆行 （Thoenen的假设）。在这项研究中，6个生理 设计实验以最大程度地区分两种模型。Exp 1：神经生长因子（NGF）或脑源性神经营养因子（BDNF） 将直接注入小猫的视觉皮层一周， 单眼眼睑缝合。眼优势分布的变化， 模型1或2或两者都不支持，将在不同模型之间进行比较。 两种NT的浓度。实验2：两个NT中的每一个将被输注为 实验1，但眼睛将不受影响，以研究竞争的影响， 自然水平。这将允许检查NT的直接化学作用 大脑皮层的活动实验3：作为实验2的对照，NT输注，否则 在NT输注的一周内，将正常的小猫保持在黑暗中。 实验4：将研究NT输注的影响与一种不寻常的 注射河豚毒素的眼睛和眼睛之间的双眼相互作用水平 对侧眼睑缝合。 实验5：NT将被注入视觉皮层， 双眼失明的小猫最后两项准备工作包括在内，因为 上述两种模型之间的区别很强，或者 如果NTs的具体作用是可检测的，则为中度。实验6：我们将学习 在其他体内系统中显示的NT的快速生理作用是否也 在全身麻醉下诱导眼优势的变化， 瘫痪实验7：我们将检查直接注入的皮质内扩散 使用由此获得的“体内稀释曲线”，我们 将滴定最低但有效的BDNF浓度， 生理效应。