Neural sequences for planning and production of learned vocalizations

项目摘要 神经元活动序列被认为是计划、准备和产生自愿的 熟练的行为。解剖这些前运动和运动序列是如何在功能和突触上的 整合以支持自然行为的流畅、与上下文相适应的表现是一项主要研究 这是一项挑战，也是大脑倡议的一个核心目标。鸣禽运动前皮质结构HVC(使用字母 顾名思义)已经成为研究稀疏神经序列 这是一种精确的、与行为相关的行为--鸟鸣的基础。单一类别的投影 HVC内的神经元是鸟鸣急性表演所必需的。然而，与电池相关的技术限制- 对这些神经元的类型选择性监测和操作阻碍了研究它们的神经如何 序列在功能和语法上进行了集成，以支持计划、准备和执行 行为。我们已经开发了群体钙成像和光发育的细胞类型特异性方法。 并展示了它们在解剖下丘脑室旁核的功能和突触组织方面的价值 在歌唱的鸟儿中巡回演出。我们的初步结果支持HVC职能组织的新模式 在这项提议的四个目标中得到了检验。我们将使用钙成像，电生理记录和 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， 以及电路标测方法，以测试该电路的功能、突触和区域组织。在图形上绘制 各种尖端方法和三个科学小组的综合专业知识，这项研究旨在 提供一个新的功能模型，说明不同的神经序列是如何通过突触整合来支持流畅的 产生一种自愿的熟练行为。

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.