Neural sequences for planning and production of learned vocalizations

项目摘要 神经元活动的顺序被认为是计划，准备和生产自愿 熟练的行为。剖析这些前运动和运动序列是如何在功能和突触 集成以支持流畅，上下文适当的自然行为表现是一个主要的研究 挑战和BRAIN倡议的中心目标。鸣禽运动前区皮质结构HVC（使用字母 作为专有名称）已经成为研究稀疏神经序列如何 构成了一种精确的、与动物行为学相关的行为--鸟鸣的基础。一类投影 HVC中的神经元对于鸟鸣的急性表现是必需的。然而，与细胞相关的技术限制- 对这些神经元的类型选择性监测和操纵阻碍了研究它们的神经元如何被激活的能力。 序列在功能上和突触上整合，以支持计划、准备和执行， 行为我们已经开发了细胞类型特异性的方法，用于群体钙成像和光遗传学 操纵HVC，并证明他们的价值解剖的功能和突触组织，这 在歌唱的鸟儿中盘旋。我们的初步结果支持一个新的模型HVC功能组织，将 在这四个目标的考验。我们将使用钙成像，电生理记录， 在自由歌唱的鸟类中进行光遗传学操作，以测试HVC中不同的神经序列是如何构成 歌曲的策划、准备和制作。此外，我们将使用单细胞光遗传学，钙成像， 和电路映射方法来测试该电路的功能、突触和区域组织。借鉴一 各种尖端方法和三个科学小组的综合专业知识，这项研究的目的是 提供了一个新的功能模型，用于研究不同的神经序列如何在突触上整合，以支持fluent 一种自愿的熟练行为的产生。

Project Summary Sequences of neuronal activity are thought to underlie planning, preparation, and production of voluntary skilled behaviors. Dissecting how these premotor and motor sequences are functionally and synaptically integrated to support fluent, context-appropriate performance of natural behaviors is a major research challenge and a central goal of the BRAIN Initiative. The songbird premotor cortical structure HVC (letters used as proper name) has emerged as a prominent model system for studying how sparse neural sequences underlie the production of a precise, ethologically relevant behavior - birdsong. A single class of projection neurons in HVC is necessary for acute performance of birdsong. Yet, technical limitations associated with cell- type selective monitoring and manipulation of these neurons has hindered the ability to study how their neural sequences are functionally and synaptically integrated to support the planning, preparation and execution of behavior. We have developed cell-type specific methods for population calcium imaging and optogenetic manipulations in HVC and demonstrate their value in dissecting the functional and synaptic organization of this circuit in singing birds. Our preliminary results support a new model for HVC functional organization that will be tested in the four aims of this proposal. We will use calcium imaging, electrophysiological recordings and optogenetic manipulations in freely singing birds to test how diverse neural sequences in HVC underlie the planning, preparation and production of song. In addition, we will use single-cell optogenetics, calcium imaging, and circuit mapping methods to test the functional, synaptic and areal organization of this circuit. Drawing on a variety of cutting-edge approaches and the combined expertise of three scientific groups, this research aims to provide a new functional model for how diverse neural sequences are synaptically integrated to support fluent production of a voluntary skilled behavior.