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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。

基本信息

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
项目类别：
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

项目摘要

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.