Conte Centers for the Neuroscience of Depression

孔特抑郁症神经科学中心

• 批准号: 7138852
• 负责人: RANGA R KRISHNAN
• 金额: $ 198.55万
• 依托单位: DUKE UNIVERSITY
• 依托单位国家: 美国
• 财政年份: 2001
• 资助国家: 美国
• 起止时间: 2001-09-01 至 2011-07-31
• 项目状态: 已结题
• 来源: https://reporter.nih.gov/project-details/7138852
• 关键词: clinical research; depression; neurobiology; pathologic process

Description (Provided by Applicant): The proposed Silvio O. Conte Center for Neuroscience of Depression will focus on understanding the neurobiological mechanism of depression. A total of 5 projects are proposed. The center is focused on a single hypothesis. The first project examines localization of lesions, structural changes in critical regions subserving the circuit, alterations in the white matter tracts relevant to the circuit and changes in glutamate. The second project uses post mortem cell counting and cellular localization in serotonin receptors and assessment of the type of cell loss in the orbitofrontal cortex. The third project uses cognitive paradigms and functional MRI to probe the circuit and the role of brain lesions and serotonin on the functioning of this circuit. The fourth project uses transgenic and knockout mice to examine to role of norepinephrine and serotonin as it relates to the circuit. The final project is designed to assess in these transgenic mice using multielectrode array of single neuron recordings of the firing pattern of the circuit neurons in various states and tasks and the role of monoamines in modulating this circuit. Three shared resources, administrative, research and assessment and data management/statistics are proposed to facilitate the conduct of these projects and to ensure integration at the conceptual, analytical and resource availability level, and flow to the various projects. Findings from the center should greatly enhance our understanding of the biology of depressive disorders and help improve the treatment of these disorders. In addition, the technological innovations developed in the context of this project are likely to be of major importance and relevant to other studies of brain function.

描述（由申请人提供）： 拟建的西尔维奥·孔特抑郁症神经科学中心将重点研究抑郁症的神经生物学机制。共拟建5个项目。该中心专注于单一假设。第一个项目检查病变的定位、维护回路的关键区域的结构变化、与回路相关的白质束的变化以及谷氨酸的变化。第二个项目使用死后细胞计数和血清素受体的细胞定位，并评估眶额皮质细胞损失的类型。第三个项目使用认知范式和功能性 MRI 来探测回路以及大脑病变和血清素对该回路功能的作用。第四个项目使用转基因和基因敲除小鼠来检查去甲肾上腺素和血清素在回路中的作用。最终项目旨在使用单神经元的多电极阵列记录这些转基因小鼠在各种状态和任务下的电路神经元的放电模式以及单胺在调节该电路中的作用。建议采用三种共享资源，即行政、研究和评估以及数据管理/统计，以促进这些项目的开展，并确保在概念、分析和资源可用性层面上的整合，并流向各个项目。该中心的研究结果应该会极大地增强我们对抑郁症生物学的理解，并有助于改善这些疾病的治疗。此外，在该项目中开发的技术创新可能非常重要，并且与其他脑功能研究相关。