MECHANISMS OF DAMAGE-INDUCED CORTICAL PLASTICITY

身体表面在大脑中的表现，包括颅面结构的表现，作为外周损伤或经历的功能而迅速改变。三叉神经系统的实验表明，部分触须卵泡的破坏或它们正常功能输入的丧失会导致初级体感皮层（S-I）中未改变的低语表征的扩大。虽然在外周损伤或神经分化后经常出现皮层地图的快速重组，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皮层中特别相关，因为身体的不同部分（面部、前肢、后肢）在不同的组织学和细胞化学上可证明的区室中表现出来。因此，重要的是要理解，特别是在本项目的背景下，基于特定隔室（颅面表征）变化的研究结果得出的经验诱导的皮层重组的“规则”是否也适用于隔室。在之前的资助期内，我们发现新生儿前肢截肢导致脑干和丘脑皮质下解剖和功能重组，当γ -氨基丁酸（GABA）受体被阻断时，这种重组仅在S-I中表达。在GABA受体阻断后，在皮质下和皮质中观察到的功能重组的主要特征是，在通常只代表前肢的区域，神经元的接受野包括前肢残肢和后肢（分裂的Rfs）。本应用实验的总体目标是回答关于新生儿前肢切除后大鼠感觉信息重组和皮层抑制的四个问题：1)新生儿截肢大鼠GABA受体阻断后S-I神经元表达分裂Rfs的底物是什么？2)新生儿截肢动物后肢信息在脑皮层的抑制机制是什么？3)新生断肢大鼠S-I分裂Rfs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。

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.