A transgenic songbird to image brain premotor sequence

 描述(由申请人提供)：学习的运动行为背后的神经机制是神经科学中最不被理解的方面之一，然而，治疗受伤或疾病后的运动障碍是一个重要的临床需求。更好地了解运动控制的组织结构可能会导致有效的治疗，从而增强运动的可塑性，或为功能恢复提供脑机接口。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，习得的运动技能缺乏可重复性。为了对执行一种高度复杂但刻板印象的行为期间的神经元活动进行成像，我们建议开发一种表达遗传编码的钙指示物GCaMP6的转基因鸣鸟。我们将使用斑马雀，这是一种学习产生极其刻板的歌唱模式的物种，试验规模小得惊人--来试验各种变体。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的功能变化与特定的、容易测量的行为变化紧密关联起来。揭示运动行为和细胞类型特定回路活动的相关原理将为控制感觉-运动学习、损伤反应的适应性可塑性提供关键见解，也将为下一代脑机接口的发展提供见解。

 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.