The Role of the Transcallosal Pathway in Neuroplasticity Following Nerve Injury

经胼胝体通路在神经损伤后神经可塑性中的作用

基本信息

批准号：
9547079
负责人：
Galit Pelled
金额：
$ 33.76万
依托单位：
MICHIGAN STATE UNIVERSITY
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：
2017-08-18 至 2020-07-31
项目状态：
已结题

来源：
https://reporter.nih.gov/project-details/9547079
关键词：
Accidents Address Adjuvant Adult Affect American Amputees Animal Model Animals Autoimmune Diseases Behavioral Brain Characteristics Chloride Channels Clinical Contralateral Diabetes Mellitus Dopa-Responsive Dystonia Electromagnetic Fields Electromagnetics Electrophysiology (science)Equilibrium Fishes Fluorescence Functional Magnetic Resonance Imaging Functional disorder Funding Goals Grant Grooming Human Injury Interneurons Ion Channel Lead Limb structure Long-Term Depression Long-Term Potentiation Maps Mediating Membrane Metabolic Diseases Methods Molecular Nerve Neuronal Injury Neuronal Plasticity Neurons Neurorehabilitation Operative Surgical Procedures Outcome Pathway interactions Patients Peripheral Nerves Peripheral nerve injury Phantom Limb Pain Protocols documentation Rattus Recovery Rehabilitation therapy Resolution Rodent Role Sensory Slice Somatosensory Cortex Source Synaptic plasticity Technology Testing Transcranial magnetic stimulation Translating United States Up-Regulation War base behavior test chronic pain excitatory neuron functional outcomes human imaging imaging study improved in vivo inhibitory neuron injured limb injury minimally invasive multimodality neglect nerve injury nervous system disorder neurophysiology neuroregulation novel optical imaging optogenetics painful neuropathy promoter public health relevance repaired response

项目摘要

DESCRIPTION (provided by applicant): Twenty million Americans suffer from peripheral nerve injury that leads to significant changes in cortical and subcortical neuronal activity. Evidence from human imaging studies suggests that the degree of post- injury plasticity and cortical remapping may be maladaptive and positively correlated to the levels of sensory dysfunctions and phantom limb pain. In an animal model of peripheral nerve injury we demonstrated that post-injury increases in functional magnetic resonance imaging (fMRI) responses reflect in fact, increases in inhibitory interneurons activity. Thus, we hypothesize that post-injury increase in inhibitory interneurons activity delays neurorehabilitation. However, the majority of current neurorehabilitation strategies focus on surgical nerve repair which neglect to address the dramatic changes occurring in the brain level. Indeed, studies show that patients continue to suffer from sensory dysfunctions despite nerve repair surgeries. We have recently demonstrated that limb injury in adult rats induces short- and long-term plasticity changes that affect S1 activity; an effect that can be readily mapped with non-invasive, ultra-high field, and high-resolution fMRI. The plasticity was manifested in changes in the excitability of cortical laye 5 inhibitory interneurons in the affected primary somatosensory cortex (S1), and was mediated via the transcallosal projections. We used optogenetics methods to modulate cortical activity in the injured rats and successfully restored the balance between excitation and inhibition. Therefore, post-injury neuronal changes leading to a shift in the excitation-inhibition balance have the potential to be reshaped with neuromodulation strategies. The goal of this proposal is to develop state-of-the-art neuromodulation strategies to augment recovery including transcranial magnetic stimulation (TMS) and a novel, minimally-invasive, neuronal-specific technology. Utilizing multimodal technical approaches we will determine how injury affects plasticity mechanisms in the molecular, cellular, network and behavioral levels, and whether the neuromodulation strategies employed here can minimize sensory dysfunctions associated with injury and facilitate rehabilitation. We anticipate that these strategies could be translated into he clinical setting as alternatives or adjuvants to traditional surgical nerve repairs, and also be usd to modulate neuronal function in other neurological disorders.

描述（由适用提供）：两千万美国人患有周围神经损伤，导致皮质和皮质下神经元活性发生重大变化。人类影像学研究的证据表明，伤害后的可塑性和皮质重塑的程度可能是适应不良的，并且与感觉功能障碍和幻影肢体疼痛的水平正相关。在外周神经损伤的动物模型中，我们证明了伤害后功能磁共振成像（fMRI）反应的增加实际上反映了抑制性神经元活性的增加。那我们假设抑制性中间神经元活动的伤害增加延迟了神经康复。但是，当前的大多数神经康复策略都集中在手术神经修复上，这些策略忽略了解决大脑级别发生的巨大变化。实际上，研究表明，患者继续患有感官功能障碍目的地神经修复手术。我们最近证明，成年大鼠的肢体受伤会诱导影响S1活性的短期和长期可塑性变化。可以通过非侵入性，超高场和高分辨率fMRI映射的效果。可塑性表现在受影响的原发性体感皮质（S1）中皮层5抑制性中间神经元兴奋中的变化，并通过thrandcallosal突发性介导。我们使用光遗传学方法来调节受伤大鼠的皮质活性，并成功恢复了兴奋和抑制之间的平衡。因此，伤害后神经元的变化导致兴奋性抑制平衡发生变化具有通过神经调节策略重塑的潜力。该提案的目的是开发最新的神经调节策略，以增加恢复，包括经颅磁刺激（TMS）和一种新颖的，微不足道的，神经元特异性的技术。利用多模式技术方法，我们将确定伤害如何影响分子，细胞，网络和行为水平的可塑性机制，以及此处采用的神经调节策略是否可以最大程度地减少与伤害和维持康复相关的感觉功能障碍。我们预计这些策略可以被转化为临床环境，作为替代方案或适应传统的外科神经修复，也可以在其他神经系统疾病中调节神经元功能。