Mechanisms of Large-scale Reorganization in Rat Forepaw Barrel Subfiels Cortex

大鼠前爪桶状皮层大规模重组机制

• 批准号: 7807069
• 负责人: ROBERT S WATERS
• 金额: $ 25.29万
• 依托单位: UNIVERSITY OF TENNESSEE HEALTH SCI CTR
• 依托单位国家: 美国
• 财政年份: 2007
• 资助国家: 美国
• 起止时间: 2007-05-01 至 2014-04-30
• 项目状态: 已结题
• 来源: https://reporter.nih.gov/project-details/7807069
• 关键词: Accidents; Adult; Amputation; Amputees; Animals; Base of the Brain; Behavioral; Biological Models; Brain Mapping; CNS processing; Cell Nucleus; Cells; Chronic; Congenital Abnormality; Data; Deafferentation procedure; Digit structure; Disease; Disinhibition; Down-Regulation; Excision; Forelimb; Goals; Health; Histocytochemistry; Human; Image; Immobilization; Immunohistochemistry; In Situ Hybridization; Interneurons; Iontophoresis; Label; Laboratories; Lateral posterior nucleus of thalamus; Lead; Life; Limb structure; Locomotion; Maps; Movement; Neurologic; Neurons; Occupations; Pain; Pathway interactions; Peripheral; Physiological; Play; Prosthesis; Rattus; Reporting; Research Personnel; Role; Shoulder; Site; Somatosensory Cortex; Source; Staining method; Stains; Structure of nucleus cuneatus; Techniques; Testing; Time; Ventral Lateral Thalamic Nucleus; Ventral Posterior Nucleus; Water; arm; chronic pain; disability; extracellular; immunocytochemistry; in vivo; microstimulation; motor control; prevent; programs; receptive field; restoration; therapy development

DESCRIPTION (provided by applicant): There are over 1.6 million amputees living in the US and it is estimated that 3000 join their ranks each week. Limb amputation results from disease, traumatic accident, birth defects, and warfare, and often is accompanied by chronic pain, impaired locomotion, and inability to conduct bimanual tasks. Limb loss may lead to long-term disability, job loss, and represents a major worldwide health problem. Limb amputation also results in massive cortical reorganization. Understanding the central neurological consequences that follow amputation is crucial for devising therapies and developing alternative strategies to compensate for loss of limb. Incomplete understanding of the effects of forelimb amputation on central nervous system processing limits our ability to ameliorate these deficits or to develop prosthetic devices for restoration of function. Cortical reorganization is often associated with chronic limb pain; by testing hypotheses about the structural and functional bases of brain reorganization, we can hope to better understand and control chronic limb pain. The goals of this proposal are to understand the mechanisms that underlie delayed large-scale cortical reorganization that follows forelimb amputation. The rat forepaw barrel subfield in first somatosensory cortex, ventral posterior lateral nucleus (VPL), thalamic reticular nucleus (RTN), and cuneate nucleus (CN) will serve as our model systems. By using a model system and techniques in which we are expert, we will elucidate the central consequences of forelimb amputation and examine potential mechanisms that underlie cortical reorganization. The objectives of this proposal are: a) test hypotheses that delayed large-scale cortical reorganization results from changes in subcortical circuitry, b) test hypotheses that removal of GABAergic inhibition is a mechanism for cortical reorganization, c) test hypotheses that RTN and CN provide substrates for the delay component in long-term cortical reorganization, and d) test hypotheses that forelimb amputation alters intact cortex and results in deficits in fine movement in the intact limb. The proposal incorporates techniques in physiological brain mapping, microstimulation, anatomical tracing, immunocytochemistry, and in-situ hybridization histochemistry that are routinely used in our laboratories. Four Aims are proposed: Aim 1: Test hypotheses that forelimb amputation results in delayed reorganization in VPL and CN, and reorganization is under GABAergic control. Aim 2: Test hypotheses that forepaw VPL projection neurons that relay new input to FBS also provide the pathway for new input to deafferented cortex. Aim 3: Test hypotheses that RTN provides delayed inhibitory control of VPL. Aim 4: Test hypotheses that forelimb amputation also alters non-deafferented cortex and leads to deficits in fine motor control in the intact limb.

描述（由申请人提供）：在美国，有超过160万个释放者居住，估计每周有3000名加入他们的队伍。肢体截肢是由疾病，创伤事故，出生缺陷和战争引起的，并且经常伴有慢性疼痛，运动受损以及无法执行双层任务。肢体损失可能导致长期残疾，失业，并代表了全球重大的健康问题。肢体截肢还会导致大规模的皮质重组。了解截肢之后的中心神经系统后果对于制定疗法和制定替代策略以弥补肢体损失至关重要。对前肢截肢对中枢神经系统处理的影响的不完全理解限制了我们改善这些缺陷或开发假肢设备以恢复功能的能力。皮质重组通常与慢性肢体疼痛有关。通过测试有关脑重组的结构和功能碱基的假设，我们可以希望更好地理解和控制慢性肢体疼痛。该提案的目标是了解延迟的大规模皮质重组的机制，该机制遵循前肢截肢。第一体体感觉皮质，腹侧后外侧核（VPL），丘脑网状核（RTN）和Cuneate Nucleus（CN）中的大鼠枪管子场将用作我们的模型系统。通过使用我们是专家的模型系统和技术，我们将阐明前肢截肢的核心后果，并检查基于皮质重组的潜在机制。 The objectives of this proposal are: a) test hypotheses that delayed large-scale cortical reorganization results from changes in subcortical circuitry, b) test hypotheses that removal of GABAergic inhibition is a mechanism for cortical reorganization, c) test hypotheses that RTN and CN provide substrates for the delay component in long-term cortical reorganization, and d) test hypotheses that前肢截肢会改变完整的皮质，并导致完整肢体运动的细胞不足。该提案结合了生理脑作图，微刺激，解剖学跟踪，免疫细胞化学和原位杂交组织化学的技术。提出了四个目的：目标1：测试假设，即前肢截肢会导致VPL和CN中的重组延迟，并且重组在GABAERGIC控制之下。 AIM 2：测试假设的假设，即将新输入传递给FBS的VPL投影神经元也为新输入提供了新输入的途径。 AIM 3：测试假设RTN提供了对VPL的延迟抑制控制。 AIM 4：测试假设，即前肢截肢还改变了非乳皮皮层，并导致完整肢体中精细运动控制的缺陷。

项目成果

Repetitive microstimulation in rat primary somatosensory cortex (SI) strengthens the connection between homotopic sites in the opposite SI and leads to expression of previously ineffective input from the ipsilateral forelimb.

大鼠初级体感皮层 (SI) 中的重复微刺激加强了相反 SI 中同伦位点之间的联系，并导致同侧前肢先前无效的输入表达。

• DOI: 10.1016/j.brainres.2020.146694
• 发表时间: 2020
• 期刊: Brain research
• 影响因子: 2.9
• 作者: DeCosta-Fortune,TinaM;Ramshur,JohnT;Li,ChengX;deJonghCurry,Amy;Pellicer-Morata,Violeta;Wang,Lie;Waters,RobertS
• 通讯作者: Waters,RobertS