Exploring the role of the central amygdala in vocalization

描述(由申请人提供)：我提议的研究性培训的目标是探索杏仁核在对突出的声音信号产生社会适当的发声反应中的作用。拟议的实验将确定杏仁核和负责发声的区域之间的联系，沿着这些通路传递信号的化学信使，以及两条不同的神经通路对发声反应的启动和形成的贡献。之前的研究证明了杏仁核在处理社会刺激中的重要性，但对该大脑区域如何产生适合特定社会背景的行为反应知之甚少。我将在一个强大的模型系统(非洲爪哇)中研究这个问题，在这个系统中，声音交流被很好地理解，后脑声音模式产生电路被映射；独特的虚构发声可以在体外被唤起，从而促进神经电路分析。{我发现杏仁中央核的损伤会产生社交不适当的发声反应(哺乳动物的情况就是这样)，而终纹床核的损伤会导致骨痂启动的缺陷，经常导致对正常诱导的社会刺激缺乏发声反应。 我在打电话。我将使用神经解剖学、电生理学和药理学技术来研究这两种效应所涉及的特定神经通路。拟议的实验将解决四个具体目标。(1)确定刺激CEA是否足以诱导应答呼叫。电刺激CEA将被用来启动来自切除的大脑的人工应答呼叫(2)识别CEA中投射到PBN和BST的神经元。葡聚糖标记的染料和共聚焦显微镜将确定CEA中的哪些细胞投射到PBN和BST。免疫细胞化学将确定它们是否具有GABA活性。(3)确定去抑制PBN神经元是否是CEA产生应答呼叫的机制。GABA激动剂将被用来在分离的大脑中模拟CEA的输入，同时记录来自喉神经的虚构的呼叫。(4)确定刺激BST是否通过5-羟色胺能机制启动叫声。5-羟色胺能药物将被用来阻断或促进电刺激BST诱导的虚构呼叫。}通过解决这些目标，这项研究将阐明杏仁核的基本功能之一，即产生上下文适当的行为。此外，这将有助于加深对杏仁核在社会发声行为中的作用的理解，并可能对治疗沟通障碍(如言语失语、选择性沉默和口吃)以及社会认知障碍(如阿斯伯格综合征和自闭症谱系障碍)做出重要贡献。

DESCRIPTION (provided by applicant): The goal of my proposed research training is to explore the role of the amygdala in generating socially appropriate vocal responses to salient acoustic signals. The proposed experiments will identify the connections between the amygdala and the regions responsible for vocal production, the chemical messengers that convey signals along these pathways and the contributions of two distinct neural pathways to the initiation and shaping of vocal responses. Previous research demonstrates the importance of the amygdala in processing social stimuli but less is known about how this brain region generates the behavioral responses that are appropriate for a given social context. I will study this problem in a powerful model system (Xenopus laevis) in which vocal communication is well understood and the hindbrain vocal pattern generating circuit is mapped; distinctive fictive vocalizations can be evoked ex vivo facilitating neural circuit analyses. {{I have found that lesions of the central amygdala produce socially inappropriate vocal responses (as is the case for mammals), and that lesions of the bed nucleus of the stria terminalis produce deficits in the initiation of callig, frequently resulting in the lack of vocalization in response to social stimuli that normally induce calling. I will investigate the specific neural pathways involved in these two effects using neuroanatomical, electrophysiological and pharmacological techniques. The proposed experiments will address four specific aims. (1) Determine whether stimulation of the CeA is sufficient to induce answer calling. Electrical stimulation of the CeA will be used to initiate ficive answer calling from the excised brain (2) Identify the neurons in the CeA that project to the PbN and the BST. Dextran-conjugated dyes and confocal microscopy will determine which cells in the CeA project to the PbN and BST. Immunocytochemistry will determine whether they are GABAergic. (3) Determine whether disinhibition of PbN neurons is the mechanism through which the CeA produces answer calling. GABA agonists will be used to mimic input from the CeA in the isolated brain while recording fictive calling from the laryngeal nerve. (4) Determine whether stimulation of the BST initiates calling through a serotonergic mechanism. Serotonergic drugs will be used to block or facilitate fictive calling induced by electrical stimulation of the BST.}} By addressing these aims, this research will illuminate one of the fundamental functions of the amygdala, the generation of context-appropriate behavior. Further, it will contribute to a growing understanding of the role of the amygdala in social vocal behavior and could make important contributions to the treatment of communication disorders, such as speech aphasias, selective mutism, and stuttering, and social cognition disorders, such as Asperger's syndrome and autism spectrum disorders.