MECHANISMS OF DAMAGE-INDUCED CORTICAL PLASTICITY

损伤引起的皮质可塑性机制

• 批准号: 6584619
• 负责人: ROBERT W RHOADES
• 金额: $ 9.05万
• 依托单位: WASHINGTON UNIVERSITY
• 依托单位国家: 美国
• 财政年份: 2002
• 资助国家: 美国
• 起止时间: 2002-04-01 至 2003-03-31
• 项目状态: 已结题
• 来源: https://reporter.nih.gov/project-details/6584619
• 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征，包括颅面结构的表征，随着周围损伤或经验的变化而迅速变化。三叉神经系统的实验表明，部分触须毛囊的破坏或正常功能输入的丧失会导致初级体感皮层（S-I）中未改变的耳语表征的扩展。虽然皮层图谱的快速重组经常出现在外周损伤或传入神经阻滞之后，但这些变化似乎存在明显的空间限制。这些限制可能与啮齿动物皮层特别相关，其中身体的不同部分（面部、前肢、后肢）代表不同的组织学和细胞化学可证明的区室。因此，重要的是要了解，特别是在本计划项目的背景下，基于对给定区室（颅面表征）内变化的研究得出的结果的经验诱发的皮质重组的“规则”是否也适用于跨区室。在之前的资助期间，我们发现，新生儿前肢截肢会导致脑干和丘脑皮质下解剖和功能重组，而当γ-氨基丁酸（GABA）受体被阻断时，这种重组仅在 S-I 中表达。 GABA 受体阻断后，在皮层下和皮层中观察到的功能重组的一个重要特征是，神经元的感受野包括前肢残端和后肢（分裂 Rfs），而这些区域通常只代表前肢。本申请实验的总体目标是回答关于新生大鼠前肢切除后观察到的感觉信息的重组和皮层抑制的四个问题：1）新生截肢大鼠 GABA 受体阻断后 S-I 神经元表达的分裂 Rfs 的底物是什么？ 2）新生截肢动物皮质后肢信息抑制的机制是什么？ 3）新生断肢大鼠S-I中具有分裂Rfs的神经元发育的必要条件是什么？ 4）分裂Rfs功能抑制的必要条件是什么？我们将采用广泛的生理学和解剖学方法来回答所有这些问题。