DEVELOPING NEW TOOLS TO UNDERSTAND THE ROLE OF INTERNEURONS IN REWIRING AFTER SPINAL CORD INJURY.

开发新工具来了解中间神经元在脊髓损伤后重新布线中的作用。

• 批准号: 9452717
• 负责人: Shelly Elese Sakiyama-Elbert
• 金额: $ 30.02万
• 依托单位: UNIVERSITY OF TEXAS AT AUSTIN
• 依托单位国家: 美国
• 财政年份: 2017
• 资助国家: 美国
• 起止时间: 2017-02-01 至 2020-01-31
• 项目状态: 已结题
• 来源: https://reporter.nih.gov/project-details/9452717
• 关键词: Ablation; Affect; Aftercare; American; Amyotrophic Lateral Sclerosis; Animal Model; Behavioral; Biological Assay; Biological Models; Cells; Clinical; Closure by clamp; Combined Modality Therapy; Corticospinal Tracts; Cues; Development; ES Cell Line; Electrophysiology (science); Environment; Event; Fiber; Flow Cytometry; Frequencies; Future; Generations; Genetic; Growth Factor; Image; Immunohistochemistry; In Vitro; Inflammation; Injury; Interneurons; Intervention; Island; Knowledge; Label; Lateral; Link; Locomotion; Mammals; Modeling; Molecular; Motor; Motor Neurons; Mus; Natural regeneration; Neonatal; Neurodegenerative Disorders; Neurons; Pattern; Population; Property; Puromycin; Quality of life; Rattus; Recovery of Function; Reporter; Research; Reverse Transcriptase Polymerase Chain Reaction; Rodent Model; Rogaine; Role; Spinal; Spinal Cord; Spinal cord injury; Spinal cord injury patients; Stem cells; Synapses; Target Populations; Testing; Therapeutic; Tissues; Transferase; Transgenic Mice; Transgenic Organisms; Transplantation; United States; Walking; axon regeneration; cell growth; central pattern generator; embryonic stem cell; extracellular; fictional works; functional improvement; immunocytochemistry; in vitro Model; microdevice; promoter; public health relevance; relating to nervous system; response; synaptogenesis; tool; transcription factor; transgene expression

 DESCRIPTION (provided by applicant): Spinal cord injury (SCI) is a debilitating condition that results in significant loss of motor function and reduction in quality of life for the approximatel 265,000 Americans affected. For many years, a dogma held by those studying SCI was that long-range regeneration of descending tracts was the key to regaining function. However, more recent research has shown that functional recovery is due to local rewiring of these tracts to propriospinal neurons and plasticity of spared neural tissue within the spinal cord. To better understand how this regeneration occurs, we need to identify which neuronal populations are involved in these local rewiring events after SCI. While the local circuitry that contributes to locomotion via central pattern generators is well defined in model organisms, the full details of the interneuron (IN) circuitry contributing to rhythm generation and frequency modulation are still being defined in mammals. Currently, very few examples exist with firm links between developmental identity, as assessed by molecular and/or transcription factor profiles, and functional identity, as assessed by electrophysiology and/or connectivity patterns. New tools are needed to better understand the role of different spinal INs populations in functional recovery after SCI and to develop potential interventions to target these populations. This project will develop tools to isolate and culture ventral spinal neuron populations. We will develop an in vitro platform that will allow us to study connectivity between INs, motoneurons (MNs), and cortical neurons in a model system and to define cues that promote functional connectivity of these networks. Finally, we will examine the contributions of transplanted spinal MN and IN populations to functional recovery in a rat model of spinal cord injury.

 描述（由申请人提供）：脊髓损伤（SCI）是一种使人衰弱的疾病，导致大约265，000名受影响的美国人的运动功能显著丧失和生活质量降低。 许多年来，SCI研究者一直坚持的一个信条是，下行神经束的长距离再生是恢复功能的关键。 然而，最近的研究表明，功能恢复是由于这些神经束与脊髓本体神经元的局部重新连接和脊髓内备用神经组织的可塑性。 为了更好地理解这种再生是如何发生的，我们需要确定哪些神经元群体参与了SCI后的这些局部重新布线事件。 虽然通过中枢模式发生器有助于运动的局部电路在模型生物体中被很好地定义，但是有助于节律产生和频率调制的中间神经元（IN）电路的全部细节仍然是未知的。 在哺乳动物中被定义。 目前，很少有例子存在与发展的身份，如评估的分子和/或转录因子谱，和功能的身份，如评估的电生理学和/或连接模式之间的牢固联系。 需要新的工具来更好地了解不同的脊髓神经内分泌人群在SCI后功能恢复中的作用，并开发针对这些人群的潜在干预措施。 本项目将开发分离和培养腹侧脊髓神经元群体的工具。 我们将开发一个体外平台，使我们能够在模型系统中研究IN，运动神经元（MN）和皮层神经元之间的连接，并定义促进这些网络功能连接的线索。 最后，我们将在大鼠脊髓损伤模型中研究移植的脊髓MN和IN群体对功能恢复的贡献。