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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.