The role of perineuronal nets in the stabilization of birdsong behavior and neural circuits

许多（如果不是全部的话）神经回路是在高度可塑性的发育时期形成的，这一时期被称为关键期或敏感期。在关键时期控制可塑性的一般机制尚不清楚，了解控制神经可塑性的过程可能会提供对控制神经系统形成和功能的基本机制的见解。这些研究将研究调节可塑性的基本机制。一个可能限制可塑性的有希望的候选者是细胞外涂层，被称为神经周围网络，当关键时期关闭时，它出现在特殊的神经元子集周围。在鸟鸣系统中，能否通过移除周围神经网络，重新开启声音关键期，改变大脑，将是一个未知数。鸟鸣是学习发声的最佳实验模型（例如，人类的语言）。因为鸣声作为一个整体，在线的，每时每刻报告了潜在的神经回路的状态，鸟鸣模型可能被证明是一个非常宝贵的工具，可以动态探索一般关键时期的发展机制，包括感觉关键时期。这些知识将进一步了解神经可塑性及其局限性。这些研究还将开发一种潜在的试剂，用于重新打开人类声音的可塑性，即破坏神经周围网络的酶软骨素酶。与这项工作相关的更广泛的影响包括在进行拟议的研究时对本科生和研究生的培训。此外，PI将提供社区外展服务，包括参加大脑意识周、明尼苏达州大脑蜜蜂和通过实验室参观和外展到当地学校培训高中教师。

Many, if not all, neural circuits are sculpted during developmental periods of heightened plasticity known as critical or sensitive periods. General mechanisms that gate plasticity during critical periods are not known, and understanding the processes that control neural plasticity may provide insights into fundamental mechanisms that govern nervous system formation and function. These studies will examine fundamental mechanisms that regulate plasticity. A promising candidate that may limit plasticity is an extracellular coating, known as a perineuronal net that appears around a special subset of neurons when critical periods close. Whether a vocal critical period can be reopened and the brain changed by removing perineuronal nets will be determined in the birdsong system. Birdsong is the best experimental model of learned vocalization (e.g., speech in humans). Because song reports the status of the underlying neural circuit as a whole, on-line, and moment-by-moment, the birdsong model may prove an invaluable tool for dynamically probing the developmental mechanisms that underlie critical periods in general, including sensory critical periods. This knowledge will further understanding of neural plasticity and its limitations. These studies will also develop a potential reagent for reopening vocal plasticity in humans, the enzyme chondroitinase that destroys perineuronal nets. The Broader Impacts associated with this work include training of undergraduates and graduate students while performing the proposed research. In addition, the PI will provide community outreach, including participation in Brain Awareness Week, the Minnesota Brain Bee and training of high school teachers through lab tours and outreach to local schools.