Synaptic and circuit mechanisms of learned motor sequences

项目总结/摘要 这个项目旨在研究使学习复杂行为的电路机制，例如 拉小提琴或者打网球。目前，产生的过程 人们对神经网络的这些行为序列知之甚少。具体而言， 各种细胞类型对这种网络行为的研究仍然不足。这里我们考虑一个重要的发动机 斑胸草雀的一个控制核，称为HVC（以前称为高音中心），它产生 学习求偶歌曲时的神经序列。我们的建议集中在本地电路 interneurons，这是唯一的来源抑制这个网络。有几种型号已经 提出解释抑制在歌曲产生中的作用，但共识仍然难以捉摸。测试这些 模型，我们提出了一系列的电生理学，成像和光遗传学研究，使我们能够 有选择地操纵和监测HVC中间神经元，通常是在歌曲产生的背景下。 在目标1中，我们将从突触后的角度研究抑制的作用。的主要重点 目的是在鸣唱产生期间记录到HVC投射神经元上的抑制性突触电流。 在目标2中，我们将从突触前的角度，通过直接测量 在歌唱过程中识别出的中间神经元群体。我们还将评估个人 使用解剖学和电生理学方法对网络上的中间神经元进行分析。 在目标3中，我们将使用体内和体外测量来表征HVC的遗传亚型 并区分它们在网络中的角色。

Project Summary/Abstract This project aims to investigate the circuit mechanisms that enable learned complex behaviors, such as playing the violin or hitting a tennis forehand. At present, the processes which underlie the generation of these behavioral sequences by neural networks are poorly understood. Specifically, the contributions of various cell types to this network behavior remain underexplored. Here we consider an important motor control nucleus in the zebra finch called HVC (formerly known as the high vocal center), which produces neural sequences during the performance of the learned courtship song. Our proposal focuses on local circuit interneurons, which represent the sole source of inhibition to this network. Several models have been proposed to explain the role of inhibition in song production, but consensus remains elusive. To test these models, we propose a series of electrophysiological, imaging, and optogenetic studies that will enable us to manipulate and monitor HVC interneurons selectively, often in the context of song production. In Aim 1, we will examine the role of inhibition from a postsynaptic perspective. The primary focus of this aim is to record inhibitory synaptic currents onto HVC projection neurons during song production. In Aim 2, we will examine the role of inhibition from a presynaptic perspective by directly measuring populations of identified interneurons during singing. We will also gauge the impact of individual interneurons on the network using anatomical and electrophysiological methods. In Aim 3, we will use in vivo and in vitro measurements to characterize the genetic subtypes of HVC interneurons and to distinguish their roles within the network.