Neural substrates for matching hearing to utterance

描述（由申请人提供）：所有声音交流系统的共同点是听和说的匹配。这种匹配可以通过学习（如唱歌的鸟类或人类）来实现，也可以是天生的或很大程度上未经学习（如青蛙或非人类灵长类动物），但在这两种情况下，强烈的选择压力塑造了对特定声音信号产生适当声音反应的能力。产生声音反应的神经网络是如何完成这项任务的，部分原因是大多数实验系统的复杂性，我们还没有很好地理解。本研究的长期目标是通过探索一个完善的模型系统来理解听觉/声音交流的神经机制：南非爪蟾的声音交流。声音产生背后的神经回路的许多方面已经被研究出来，并且一个简化的准备——孤立的大脑——可以被诱导产生有效的呼叫。我们对了解前脑核腹侧纹状体（VST）的作用特别感兴趣，它在非洲爪蟾的声音回路中是独一无二的，它接收听觉信息并直接投射到主要的后脑传入的声音运动神经元，核DTAM。本研究计划的中心假设是，VST参与选择适当的声音模式，以响应特定的声音输入。为了研究这一假设，我们首先需要额外的信息，了解VST是如何作为前运动核和听觉核发挥作用的。声音信号的产生是由一组神经调节剂控制的，这些神经调节剂的作用取决于内分泌状态。因此，本阶段研究的另一个目标是了解神经内分泌因子（如促性腺激素）和神经调节剂（如血清素）如何影响声带回路中VST的功能。我们的实验方法结合了体外和体内的方法。我们使用最近开发的分离脑准备来理解听觉/声音神经回路的各个组成部分在声音反应中的参与；细胞和分子方法结合刺激和电生理记录。我们将在体内测试提出的机制，以确定它们是否在多大程度上真正参与动物发声行为的内源性控制。前脑影响声音输出的能力可能来源于一组古老的神经连接，这些神经连接在一些脊椎动物中得到了详细阐述。如果是这样的话，非洲爪蟾的前脑/后脑、听觉/发声系统应该会为我们提供非常有趣的见解，让我们了解神经网络在交流中的作用，以及如何治疗交流障碍。几种人类语言障碍可归因于听觉/声音联系功能受损。语言习得前的耳聋对发展和交际能力有深远的影响[64]。当学龄前语聋成人接受人工耳蜗植入后，语音产生的质量随着语音感知的提高而提高[65]。通常被认为起源于运动的发音障碍，如口吃和失语症，可以通过在社会环境中传递的听觉线索（如合唱[66]和唱歌[67]）得到改善，有时效果相当显著。特别是合唱说话的效果，被认为是由“镜像神经元”系统介导的，该系统一般支持模仿，特别是声音模仿。形成“镜像神经元”系统的基础，该系统被认为在人类语言和学习鸟类鸣叫中起作用。事实上，前脑中的听觉/声音联系可能源于一套古老的进化机制，这些机制将听觉与话语联系起来。如果是这样，了解非洲爪蟾的听觉/声音匹配可以提供一套候选的神经机制，其普遍性和实用性可以更广泛地研究。

DESCRIPTION (provided by applicant): Common to all vocal communication systems is matching between hearing and utterance. The match can be achieved via learning (as in song birds or humans) or be innate or largely unlearned (as in frogs or non-human primates), but in both cases strong selective pressures have shaped the ability to produce appropriate vocal responses to specific acoustic signals. How this task is accomplished by the neural networks that produce vocal responses is not well understood in part because of the complexity of most experimental systems. The long-term goal of this research is to understand neural mechanisms for auditory/vocal communication through exploration of a well-established model system: vocal communication in the South African clawed frog, Xenopus laevis. Many aspects of the neural circuitry underlying vocal production have been worked out and a reduced preparation - the isolated brain- can be induced to produce fictive calling. We are particularly interested in understanding the role of a forebrain nucleus, the ventral striatum (VST) which - uniquely in the Xenopus vocal circuit - receives auditory information and projects directly to the major hindbrain afferent of vocal motor neurons, nucleus DTAM. The central hypothesis of this research program is that the VST participates in selecting an appropriate vocal pattern in response to specific acoustic input. To investigate this hypothesis we first need additional information about how the VST functions as a pre-motor and an auditory nucleus. Production of vocal signals is controlled by a set of neuromodulators whose effects depend on endocrine state. Thus an additional goal of this phase of the research is to understand how neuroendocrine factors such as gonadotropin and neuromodulators such as serotonin affect the function of the VST in the vocal circuit. Our experimental approaches combine in vitro and in vivo methods. We use the isolated brain preparation we have recently developed to understand the participation of various components of the auditory/vocal neural circuit in the vocal response; cellular and molecular approaches are combined with stimulation and electrophysiological recording. We will test proposed mechanisms in vivo to determine to what extent whether they actually participate in the endogenous control of vocal behavior in the animal. The ability of forebrain to influence vocal output could derive from an ancient set of neural connections that have been elaborated in some vertebrates. If so, the forebrain/hindbrain, auditory/vocal system in Xenopus laevis should provide very interesting insights into the ways in which neural networks for communication can function as well as suggesting ways in which communication disorders can be treated. PUBLIC HEALTH RELEVANCE Several human speech disorders are attributable to impaired function of auditory/vocal linkages. Deafening before language acquisition has profound effects on development and communicative skills [64]. When prelingually deaf adults receive cochlear implants, the quality of the speech production improves along with speech perception [65]. Articulation disorders, which are commonly regarded as motor in origin, such a stuttering and aphasia, can improve, sometimes quite dramatically, by auditory cues delivered in a social context such as choral speaking [66] and singing [67]. The effects of choral speaking, in particular, have been proposed to be mediated by the "mirror neuron" system that supports imitation in general and vocal imitation in particular. form the basis for "mirror neuron" systems proposed to function in human speech and learned bird song. Auditory/vocal linkages in forebrain may, in fact, arise from a set of evolutionarily ancient mechanisms that link hearing to utterance. If so, understanding auditory/vocal matching in Xenopus could provide a set of candidate neural mechanisms whose prevalence and utility can then be investigated more widely.