Defining the Multisynaptic Circuitry of the Amygdala

定义杏仁核的多突触回路

• 批准号: 6850889
• 负责人: Lisa Stefanacci
• 金额: $ 9.31万
• 依托单位: SALK INSTITUTE FOR BIOLOGICAL STUDIES
• 依托单位国家: 美国
• 财政年份: 2004
• 资助国家: 美国
• 起止时间: 2004-03-01 至 2006-02-28
• 项目状态: 已结题
• 来源: https://reporter.nih.gov/project-details/6850889
• 关键词: Macaca mulatta; amygdala; behavioral /social science research tag; emotions; functional magnetic resonance imaging; herpes simplex virus 1; magnetic resonance imaging; method development; neural information processing; neural transmission; neuroanatomy; neuronal transport; neurotropic virus; positron emission tomography; rabies virus; reagent /indicator; synapses

DESCRIPTION (provided by applicant): The long-term objective of this study is to understand the neural circuitry underlying emotional behavior in primates. The proposed experiments focus on the transynaptic circuitry of the amygdala, a structure in the medial temporal lobe that is important for emotion, and in humans has been linked with clinical disorders such as affective illness, anxiety, autism, and schizophrenia. Our understanding of the mechanisms underlying these disorders relies in great part on our ability to understand the precise flow of information through the amygdala and neuroanatomically related regions. The organization of monosynaptic connections within the primate amygdala has been identified in great part in previous studies. However, because of the complexity of intrinsic amygdala connections and because of the limitations of classic neuronal tracers, it has been extremely difficult to identify the multisynaptic pathways, or the functional flow of information, through the amygdala. The present study will apply the use of a new class of transneuronal tracers, live neurotropic viruses, to identify chains of synaptic connections within the primate amygdala. The viral tracing method will be developed in the context of one specific research question with the goal of applying this to future, larger scale studies of amygdala circuitry. The specific aim of the present study is to identify the functional pathway(s) between two nuclei of the amygdala, the lateral nucleus, a major recipient of cortical inputs to the amygdala, and the central nucleus, one of the major output nuclei of the amygdala. These studies will reveal whether information flow from the lateral nucleus to the central nucleus involves only a monosynaptic connection or whether two or more synapses are involved. This will not only provide valuable data on the circuitry of the amygdala, but will provide the scientific community with a new methodology to more broadly understand information flow through the amygdala. Understanding the functional organization of the amygdala is a crucial step towards the ultimate goal of this research program: to obtain information that will aid in the treatment of neurological and psychiatric disorders of emotion caused by trauma, disease, and developmental defects. This goal is pertinent to a variety of clinical applications, including the development of pharmacological and behavioral treatment programs for patients who suffer with emotional disorders.

描述（由申请人提供）：这项研究的长期目标是了解灵长类动物中情感行为的神经回路。拟议的实验集中于杏仁核的透射电路，杏仁核（内侧颞叶中的结构对情绪都很重要，在人类中与临床疾病有关，例如情感疾病，焦虑，自闭症和精神分裂症。我们对这些疾病背后的机制的理解在很大程度上取决于我们通过杏仁核和神经解剖学上相关的区域来理解信息流动的能力。在先前的研究中，已经确定了灵长类动物杏仁核内的单突触连接的组织。但是，由于固有的杏仁核连接的复杂性以及经典神经元示踪剂的局限性，因此很难识别多突触途径或通过杏仁核的功能流动。 本研究将应用一类新的跨神经元示踪剂，即活神经性病毒，以识别灵长类动物杏仁核内突触连接的链。病毒追踪方法将在一个特定的研究问题的背景下开发，其目的是将其应用于未来的杏仁核电路的大规模研究。本研究的具体目的是确定杏仁核的两个核之间的功能途径，侧核，杏仁核的皮质输入的主要接受者和中央核，杏仁核的主要输出核之一。这些研究将揭示信息从外侧核向中心核的流动是否仅涉及单突触连接，或者是否涉及两个或更多突触。这不仅将提供有关杏仁核电路的有价值数据，而且还将为科学界提供一种新的方法，以更广泛地了解通过杏仁核的信息流。 了解杏仁核的功能组织是朝着该研究计划的最终目标迈出的至关重要的一步：获取将有助于治疗由创伤，疾病和发育缺陷引起的情绪神经和精神疾病的信息。该目标与各种临床应用有关，包括针对患有情绪障碍的患者的药理和行为治疗计划的制定。