Preservation of sensory la afferent boutons on motoneurons after peripheral nerve injury restores synaptic transmissions and rescues whole limb kinematics

周围神经损伤(PNI)后，感觉和运动神经元(MN)轴突均在损伤部位变性。 受伤，但两者都会再生到肌肉目标。运动神经元重新获得产生肌肉力量的能力 近一半的Ia组肌肉本体感受器重新支配肌梭，并对 肌肉长度。然而，在PNI之后仍然存在的一个缺陷是Ia的中央投影分支 与MNS形成单突触连接的传入神经元死亡并与运动池断开， 即使肌梭感受器暂时成功地重新支配，也永远不会再回来。这个突触 缩回对常见的运动活动有重大影响，因为中央运动网络失去了反馈 姿势调整所需的机制。这种Ia突触丢失依赖于促炎因子 脊髓腹角的免疫反应。但是，使用 广谱抗生素米诺环素，完全防止Ia传入传入的结构性损失 轴突切除的MNS。然而，主要的问题仍然存在，“这些保留下来的突触输入功能正常吗？”和 “保留Ia‘s能促进运动行为的恢复吗？”目的：研究突触功能 PNI后保留Ia传入与MN之间的连接时的运动行为。 具体目标1，假设：抢救Ia-MN脊髓环路网络将促进肢体恢复 有动静。 特定目标2，假设：物理保存将挽救Ia所形成的突触的功能 运动神经元上的传入神经。 特定目标3，假设：Ia突触电流的放大足以恢复持续的放电 在受伤后的运动神经元。 这些目的是为了系统地询问保存下来的Ia传入突触在 神经损伤。所有这些实验都将在佐治亚理工学院的赞助商Dr。 Tim Cope，以及我们的合作者张英辉博士的补充指导。两家公司都提供了他们的 在这个项目的开发方面具有专业知识，并将监督所有这三个目标的成功。

Following peripheral nerve injury (PNI), both sensory and motoneuron (MN) axons degenerate at the site of injury, but both regenerate to their muscle targets. Motoneurons regain the ability to produce muscle force and almost half of group Ia muscle proprioceptors reinnervate muscle spindles and fire in response to changes in muscle length. However, one deficit that remains after PNI is that the central projecting branch of the Ia afferents that forms monosynaptic connections with the MNs dies back and disconnects from the motor pool, never to return even with provisionally successful reinnervation of muscle spindle receptors. This synaptic retraction has a major impact on common motor activities as the central motor network losses the feedback mechanism necessary for postural adjustments. This Ia synaptic loss is dependent on a pro-inflammatory immune response in the ventral horn of the spinal cord. However, suppressing the immune response using the broad-spectrum antibiotic minocycline, completely prevents the structural loss of Ia afferent inputs on axotomized MNs. However, the major questions remain, “are these preserved synaptic inputs functional?” and “does preservation of Ia’s improve recovery of motor behavior?” Objective: Investigate synaptic function and motor behavior when the connections between Ia afferents and MNs are preserved following PNI. Specific Aim 1, Hypothesis: Rescuing Ia - MN spinal circuit network will promote recovery of limb movement. Specific Aim 2, Hypothesis: Physical preservation will rescue function at synapses made by Ia afferents on motoneurons. Specific Aim 3, Hypothesis: Amplification of Ia synaptic current is sufficient to restore sustained firing in motoneurons after injury. These aims are designed to systematically interrogate the function of preserved Ia afferent synapses after nerve injury. All of these experiments will take place at Georgia Tech under the direction of the sponsor, Dr. Tim Cope, and additional guidance from our collaborator Dr. Young-Hui Chang. Both have provided their expertise in the development of this project and will oversee the success of all three aims.