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（由申请人提供）：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动发生显着变化。来自人类成像研究的证据表明，损伤后可塑性和皮质重新映射的程度可能是适应不良且呈正相关。在周围神经损伤的动物模型中，我们证明功能障碍后功能磁共振成像（fMRI）反应的增加实际上反映了抑制性的增加。中间神经元活动。损伤后抑制性中间神经元活动的增加会延迟神经康复。然而，目前的大多数神经康复策略都侧重于外科神经修复，而忽视了大脑水平发生的巨大变化，尽管研究表明患者仍然患有感觉功能障碍。我们最近证明，成年大鼠的肢体损伤会引起影响 S1 活性的短期和长期可塑性变化，这种影响可以通过非侵入性、超高场和高分辨率功能磁共振成像可塑性表现在受影响的初级体感皮层（S1）中皮质第 5 层抑制性中间神经元的兴奋性变化，并且是通过胼胝体投射介导的。我们使用光遗传学方法来调节受伤大鼠的皮层活动。并成功恢复了兴奋与抑制之间的平衡，因此，损伤后神经主导的兴奋-抑制平衡转变有可能被重塑。该提案的目标是开发最先进的神经调节策略以促进恢复，包括经颅磁刺激（TMS）和我们将利用多模式技术方法的新型微创神经元特异性技术。确定损伤如何影响分子、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限度地减少与损伤相关的感觉功能障碍并促进康复。我们预计这些策略可以作为替代方案或促进康复转化为临床环境。传统外科神经修复的佐剂，也可用于调节其他神经系统疾病的神经功能。