ROLES OF NEUROTROPHINS IN OCULAR DOMINANCE PLASTICITY

描述(摘自申请人的摘要)：神经营养因子(NTS)包括一个 在发育过程中起营养支持作用的一类大分子 大脑皮层。在成人中，它们也参与依赖活动的过程 大脑皮层。在拟议的生理实验中，我们将确定 NT在发育中眼优势可塑性调节中的作用 视觉皮质。基本上，皮质输注有两种可能的结果 关于发展双眼相互作用的NTS：一是双眼抑制 一是竞争，二是促销。这两个预测来自两个 关于内源性NTS在大脑中的体内细胞作用的相反观点。 在模式1中，NTS通常是竞争所必需，尤其是不成熟的， 轴突终末存活(在马菲的提议中的生存因素)。 NTs作为活性突触的稳定器具有更特殊的作用，其 由传入活动本身控制的释放(“特异性逆行” 在这项拟议的研究中，6名生理性的 实验旨在最大限度地区分这两种模型。Exp 1：神经生长因子(NGF)或脑源性神经营养因子(BDNF) 将被直接注入小猫的视皮层，同时持续一周 用单眼眼睑缝合术。眼球优势分布的变化 模式1或模式2或两者都不支持，将在不同的 两种NT的浓度。实验2：将两个NT分别注入为 实验1，但眼睛将不受影响地研究竞争对 自然水平。这将允许检查NTS的直接化学作用 关于大脑皮层活动。Exp 3：作为Exp 2的控件，NT-Inputed，否则 正常的小猫在接受NT注射的一周内将被关在黑暗中。 实验4：NT输注的效果将被研究与一种不寻常的 河豚毒素注射眼与正常眼的双眼相互作用水平 被眼皮缝合的同胞眼睛。实验5：NTS将被注入大鼠视皮层 被剥夺了双眼视力的小猫。最后两项准备工作包括在内，因为 上述两种模式之间的区别是强烈的还是 缓和，如果NTS的特定影响是可检测到的。例证6：我们会学习 NTS的快速生理效应是否也在其他活体系统中表现出来 在全身麻醉下诱导眼优势改变的工作和 瘫痪。实验7：我们将检查直接注入的大脑皮质内扩散 BDNF一周或更短时间。利用这样得到的“体内稀释曲线”，我们 将为其滴定BDNF的最低有效浓度 生理效应。

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.