MECHANISMS OF DAMAGE-INDUCED CORTICAL PLASTICITY

大脑中身体表面的表现，包括头面部结构的表现，作为外周损伤或经验的函数而迅速改变。在三叉神经系统中的实验表明，触须毛囊的一部分被破坏或失去正常的功能输入，会导致初级躯体感觉皮质中未改变的耳语的表征扩大(S-I)。虽然皮层地图的快速重组往往出现在外周损伤或去传入之后，但这些变化似乎有明显的空间限制。这些限制可能在啮齿类动物的皮质中特别相关，在那里，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可证明的间隔中表现出来。因此，重要的是要了解，特别是在本计划项目的背景下，基于对给定隔室(颅面部表征)内变化的研究结果而产生的经验诱导的皮质重组的“规则”是否也适用于不同的隔室。在之前的资助期间，我们发现新生儿切断前肢会导致脑干和丘脑皮质下的解剖和功能重组，这种重组只有在γ-氨基丁酸受体被阻断时才在S-I区表达。皮质下和皮质中GABA受体阻断后观察到的功能重组的特征是，在正常情况下只有前肢的区域，神经元的感受野既包括前肢残肢，也包括后肢(分离式RF)。本实验的总体目标是回答四个关于新生大鼠去前肢后感觉信息的重组和皮质抑制的问题：1)新生截肢大鼠GABA受体阻断后，S-I神经元表达分裂RF的底物是什么？2)新生截肢动物大脑皮层后肢信息抑制的机制是什么？3)新生截肢大鼠S-I区分裂RF神经元发育的必要条件是什么？4)分裂RF功能抑制的必要条件是什么？我们将使用广泛的生理学和解剖学方法来回答所有这些问题。

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.