Functional integration of elongated axon-electrode array constructs with the peri

描述（由申请人提供）： 血管疾病、创伤和癌症导致的肢体丧失目前影响着近200万美国人。这是一种毁灭性的、改变生活的疾病，目前还没有令人满意的治疗方法。创建高功能神经假体的一个主要障碍是缺乏神经接口，有效地传达宿主神经系统和外围机器人设备之间的运动和感觉信息。该项目的长期目标是开发这样一种接口，利用周围神经系统作为与神经假体相互作用的部位。这种方法旨在利用中枢神经系统的固有处理能力，并最大限度地减少对现有接口技术访问的健康组织（如大脑和肌肉）的损伤。 为了建立一种基于周围神经系统的新型神经接口，该方案采用了一种混合神经元-电子结构与宿主神经元连接。该结构由机械伸长的轴突束与微电极阵列集成组成。与将电极插入外周神经相反，所提出的策略依赖于与宿主神经系统的生物界面，这提供了界面组件之间长期接触稳定性的显著优点。 两个具体的目标是有针对性的使用建议的混合结构的方法。首先，探索了混合构建体的神经元元件与宿主神经元之间的整合机制。假设这种整合通过宿主轴突的轴突引导再生或突触整合发生。区分这两种可能性的方法包括轴突再生和突触形成的标记物的荧光免疫组织化学和宿主轴突生长的直接测量。其次，研究了混合构建体与宿主神经系统之间的功能整合程度。最初在体外检查动作电位沿着杂交构建体的传递。随后的体内研究评估了电活动传输到宿主外周和中枢神经系统，后者涉及运动皮层刺激和微电极阵列诱发的体感电位等效物的映射。用于增强功能整合的技术可包括神经胶质细胞的同时移植和营养因子的输注。 实现该项目的目标建立了与周围神经系统生物相互作用的神经接口的可行性。在短期内，这些结果将为解码混合结构微电极阵列记录的信号提供基础，然后可以用于驱动简单的机器人任务。这个项目的长期成功完成将为研究先进的神经修复术的可行神经接口创造一个新的途径。

DESCRIPTION (provided by applicant): Limb loss from vascular disease, trauma, and cancer currently affects nearly 2 million Americans. It is a devastating, life-altering condition for which no satisfactory treatment exists. A major obstacle in the creation of high-functioning neuroprosthetics is the lack of neural interfaces that efficiently convey both motor and sensory information between the host nervous system and peripheral robotic devices. The long-term objective of this project is the development of such an interface utilizing the peripheral nervous system as the site of interaction with a neuroprosthetic. This approach seeks to exploit the inherent processing power of the central nervous system and to minimize injury to healthy tissues that are accessed by existing interface technologies, such as brain and muscle. In order to create a novel neural interface based on the peripheral nervous system, this proposal employs a hybrid neuronal-electronic construct to connect with host neurons. This construct consists of mechanically elongated axonal tracts integrated with a microelectrode array. As opposed to the insertion of electrodes into peripheral nerves, the proposed strategy relies upon a biological interface with the host nervous system, which provides the significant advantage of long-term contact stability between the components of the interface. Two specific aims are targeted using the proposed hybrid-construct approach. First, the mechanisms of integration between the neuronal element of the hybrid construct and host neurons are explored. This integration is hypothesized to occur via either axon-guided regeneration of host axons or synaptic integration. Methods for differentiating these two possibilities include fluorescence immunohistochemistry for markers of axonal regeneration and synapse formation and direct measurements of host axonal growth. Second, the extent of functional integration between the hybrid construct and the host nervous system is investigated. The transmission of action potentials along the hybrid construct initially is examined in vitro. Subsequent in vivo studies assess the transmission of electrical activity to and from the host peripheral and central nervous systems, the latter involving motor cortex stimulation and mapping of somatosensory potential equivalents evoked by the microelectrode array. Techniques for enhancing functional integration may include the concurrent transplantation of glial cells and the infusion of trophic factors. Achieving the objectives of this project establishes the feasibility of a neural interface that interacts biologically with the peripheral nervous system. In the short-term, these results would provide the foundation for work to decode signals recorded by the hybrid-construct microelectrode array, which could then be used to drive simple robotic tasks. Long-term, successful completion of this project would create a new avenue for research into a viable neural interface with advanced neuroprosthetics.