A transgenic songbird to image brain premotor sequence

 描述（由申请人提供）：学习运动行为的神经机制是神经科学中最不了解的方面之一，但损伤或疾病后运动缺陷的治疗是一个重要的临床需求。更好地理解运动控制的组织可能会导致有效的治疗，提供运动可塑性的增强，或脑机接口的功能恢复。然而，在细胞水平上，人们对大脑回路如何学习和复制时间序列知之甚少。研究自然运动控制的最大挑战之一是缺乏学习运动技能的可重复性。为了在执行高度复杂但刻板的行为过程中成像神经元活动，我们建议开发一种表达遗传编码的Ca++指示剂GCaMP6的转基因鸣禽。我们将使用斑胸草雀，这种物种学会产生一种极其定型的歌曲模式，试验到试验的变化非常小。因此，该系统提供了一种罕见的模型，从该模型可以将神经元活动中的功能变化与特定且易于测量的行为变化紧密相关。揭示与运动行为和细胞类型特异性回路活动相关的原理将提供控制感觉运动学习的关键见解，对损伤的适应性可塑性，并为下一代脑机接口的开发提供见解。

 DESCRIPTION (provided by applicant): The neural mechanisms underlying learned motor behaviors are one of the least understood aspects of neuroscience, yet treatment of motor deficits after injury or disease is a significant clinical need. A better understanding of the organization of motor control could lead to effective treatments that provide enhancements of motor plasticity, or brain machine interfaces for functional restoration. However, at the cellular level, little is known about how brain circuits are able to learn and reproduce temporal sequences. One the greatest challenges involved in investigating natural motor control is the lack of repeatability of the learned motor skill. To image neuronal activity during the execution o a highly complex, yet stereotyped, behavior we propose to develop a transgenic songbird expressing the genetically-encoded Ca++ indicator GCaMP6. We will use the zebra finch, a species that learns to produce an extremely stereotyped song pattern, with strikingly small trial-to trial variations. Thus, this system provides a rare model from which to tightly correlate functional changes in neuronal activity to specific and readily measurable behavioral changes. Uncovering principles relating motor behavior and cell type specific circuit activity will provide key insights governing sensory-motor learning, adaptive plasticity in response to injury, and also provide insights for the development of next generation brain-machine interfaces.