MECHANISMS OF DAMAGE-INDUCED CORTICAL PLASTICITY

损伤引起的皮质可塑性机制

• 批准号: 6868896
• 负责人: ROBERT W RHOADES
• 金额: $ 9.55万
• 依托单位: WASHINGTON UNIVERSITY
• 依托单位国家: 美国
• 财政年份: 2004
• 资助国家: 美国
• 起止时间: 2004-04-01 至 2005-03-31
• 项目状态: 已结题
• 来源: https://reporter.nih.gov/project-details/6868896
• 关键词: GABA receptor; amputation; brain mapping; laboratory rat; limb injury; nervous system regeneration; neural plasticity; somesthetic sensory cortex

Representations of the body surface in the brain, including those of craniofacial structures, an change rapidly as a function of peripheral damage or experience. Experiments in the trigeminal system have demonstrated that destruction of a portion of the vibrissae follicles or loss of normal functional input from them results in expansion of the representations of the unaltered whispers in the primary somatosensory cortex (S-I). While rapid reorganization of cortical maps appears often after peripheral damage or deafferentation there appear to be distinct spatial limits to these changes. These limits may be particularly relevant in the rodent cortex where different portions of the body (face, forelimb, hindlimb) are represented in distinct histologically and cytochemically demonstrable compartments. Thus, it is important to understand, particularly in the context of this Program Project, whether "rules" for experience-induced cortical reorganization based on results derived from studies of changes within a given compartment (the craniofacial representation) also apply across compartments. During the previous funding period, we showed that neonatal amputation of the forelimb results in subcortical anatomical and functional reorganization in the brainstem and thalamus that is only expressed in the S-I when gamma- aminobutyric acid (GABA) receptors are blocked. The hey feature of the functional reorganization observed subcortically and in the cortex after GABA receptor blockade is neurons with receptive fields that include both the forelimb stump and the hindlimb (split Rfs) in regions where only the forelimb would normally be represented. The overall goal of the experiments in this application is to answer four questions regarding both the reorganization and cortical suppression of sensory information observed after neonatal forelimb removal in the rat: 1) What are the substrates for the split Rfs expressed by S-I neurons after GABA receptor blockade in neonatally amputated rats? 2) What is the mechanism underlying suppression of hindlimb information in the cortices of neonatally amputated animals? 3) What are the necessary conditions for development of neurons with split Rfs in S-I of neonatally amputated rats? 4) What are the necessary conditions for the functional suppression of split Rfs? We will employ a wide range of both physiological and anatomical methods to answer all of these questions.

大脑中身体表面的表示，包括颅面结构的表面，随着外围损伤或经验的函数迅速变化。三叉神经系统中的实验表明，破坏了一部分颤音卵泡或从其中的正常功能输入的丢失导致在主要体感皮质（S-I）中未更换的窃窃私语的表示。虽然在外围损伤或停用后，经常出现皮质图的快速重组，但这些变化似乎存在明显的空间限制。这些极限可能在啮齿动物皮质中特别相关，在啮齿动物的皮质中，身体的不同部分（面部，前肢，后肢）在不同的组织学和细胞化学上可证明的隔室中表示。因此，重要的是要理解，特别是在该计划项目的背景下，是否基于从给定隔室内变化（颅面表示）的研究得出的结果的“规则”是否也适用于跨隔室。在上一个融资期间，我们表明，前肢的新生儿截肢会导致皮层解剖学和功能重组在脑干和丘脑中仅在gamma-氨基丁酸（GABA）受体被阻断时在S-1中表达。 GABA受体阻滞后的皮层和皮质中观察到的功能重组的HEY特征是神经元具有接收场的神经元，其中包含前肢和后肢（分裂RFS）在只有前肢的区域中通常代表通常表示的区域。实验在本应用程序中的总体目标是回答有关大鼠新生儿前肢去除后观察到的感官信息的重组和皮质抑制的四个问题：1）S-I神经元在NeonataInationalManatiated Amputational Amputipational Amptuptatifeated Rats中S-I神经元表达的分裂RFS的底物是什么？ 2）在新生儿截肢动物的皮质中，后肢信息的抑制基础是什么？ 3）在新生儿截肢大鼠的S-I中，神经元开发神经元的必要条件是什么？ 4）功能抑制分裂RF的必要条件是什么？我们将采用广泛的生理和解剖方法来回答所有这些问题。