Conte Centers for the Neuroscience of Depression

描述(由申请人提供)： 拟议中的西尔维奥·O·孔特抑郁症神经科学中心将专注于了解抑郁症的神经生物学机制。共提出了5个项目。该中心关注的是一个单一的假设。第一个项目检查病变的定位、辅助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5-羟色胺受体的细胞定位，并评估眼眶前额叶皮质细胞丢失的类型。第三个项目使用认知范式和功能核磁共振来探索脑损伤和5-羟色胺对这一回路功能的作用。第四个项目使用转基因和基因敲除小鼠来检测去甲肾上腺素和5-羟色胺在环路中的作用。最后一个项目的目的是在这些转基因小鼠中使用单个神经元的多电极阵列记录不同状态和任务的回路神经元的放电模式，以及单胺在调节这一回路中的作用。拟议提供行政、研究和评估以及数据管理/统计三项共享资源，以便利这些项目的开展，并确保在概念、分析和资源可获得性方面的一体化，并流向各个项目。该中心的发现将极大地增强我们对抑郁障碍生物学的理解，并有助于改善这些障碍的治疗。此外，在该项目背景下开发的技术创新可能具有重要意义，并与其他大脑功能研究相关。

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.