Inhibition, Oscillations and Information Processing in Schizophrenia

精神分裂症的抑制、振荡和信息处理

• 批准号: 7883249
• 负责人: David A Lewis
• 金额: $ 209.32万
• 依托单位: UNIVERSITY OF PITTSBURGH AT PITTSBURGH
• 依托单位国家: 美国
• 财政年份: 2008
• 资助国家: 美国
• 起止时间: 2008-08-01 至 2013-06-30
• 项目状态: 已结题
• 来源: https://reporter.nih.gov/project-details/7883249
• 关键词: Inhibition; Oscillations; Information; Processing; Schizophrenia

This Conte Center for the Neuroscience of Mental Disorders (CCNMD) offers a highly interactive scientific environment that integrates the basic and clinical research activities of multiple investigators from the University of Pittsburgh's Schools of Medicine and Arts and Sciences and the adjacent Carnegie Mellon University. Collectively, the CCNMD represents a broad array of expertise spanning molecular, systems, cognitive, computational and clinical neuroscience that provides complementary approaches to testing the central hypothesis that a distinctive pattern of molecular alterations in subpopulations of GABA neurons (pathology) gives rise to conserved disturbances in cortical network oscillations (pathophysiology) that underlie the core information processing deficits (clinical syndrome) of schizophrenia. The proposed 5 projects, supported by Administrative, Clinical Services and Diagnostics, and Statistics and Data Management Cores, examine 1) molecular abnormalities in schizophrenia in distinct subsets of cortical GABA neurons thought to generate oscillatory activity (Project 1-Lewis); 2) integrated computational, electrophysiological and anatomical approaches to determine the relationship between cell type-specific cortical GABA neurotransmission and oscillations in vitro (Project 2-Ermentrout); 3) the role of GABA neurotransmission in cortical oscillations elicited by tasks that tap in non-human primates the same information processing domains that are altered in schizophrenia (Project 3-Olson); 4) specific types of information processing disturbances in schizophrenia that are linked to altered activation of, and impaired network oscillations in, certain cortical regions (Project 4-Phillips); and 5) the development of new PET imaging tools for studying the function of human cortical GABA neurons in vivo (Project 5-Mathis). The synergism and bi-directional interactions of these projects facilitates a translational approach to schizophrenia research directing at identifying pathophysiology-based targets for novel therapeutic interventions and developing biomarkers of the pathophysiology that can be used to monitor the efficacy of such interventions. Thus, the proposed Center is a multi-disciplinary effort directed at testing a mechanistic hypothesis in order to improve our understanding of a core component of the disease process of schizophrenia. In addition, the Center provides 1) a rich environment for training and career development in which individuals can become involved in studies that bring the methods and knowledge base of basic neuroscience to address critical questions in clinical schizophrenia research, and 2) a mechanism for disseminating the importance of, and the knowledge gained from, translational studies of schizophrenia to the broader scientific and lay communities.

康特精神障碍神经科学中心 (CCNMD) 提供了一个高度互动的科学环境，整合了来自匹兹堡大学医学院、艺术与科学学院以及邻近的卡内基梅隆大学的多名研究人员的基础和临床研究活动。总的来说，CCNMD 代表了涵盖分子、系统、认知、计算和临床神经科学的广泛专业知识，为测试中心假设提供了补充方法，即 GABA 神经元亚群（病理学）中独特的分子改变模式会引起皮质网络振荡（病理生理学）的保守性干扰，而皮层网络振荡是核心信息处理缺陷的基础 （临床综合症）精神分裂症。拟议的 5 个项目由行政、临床服务和诊断以及统计和数据管理核心支持，检查 1) 精神分裂症中被认为产生振荡活动的皮质 GABA 神经元不同亚群的分子异常（项目 1-Lewis）； 2) 综合计算、电生理学和解剖学方法来确定细胞类型特异性皮质 GABA 神经传递和体外振荡之间的关系（项目 2-Ermentrout）； 3) GABA 神经传递在皮层振荡中的作用，皮层振荡是由在非人类灵长类动物中利用与精神分裂症中改变的相同信息处理域的任务引起的（项目 3-Olson）； 4) 精神分裂症中特定类型的信息处理障碍与某些皮质区域的激活改变和网络振荡受损有关（项目 4-Phillips）； 5) 开发新的 PET 成像工具，用于研究人体内皮质 GABA 神经元的功能（项目 5-Mathis）。这些项目的协同作用和双向相互作用促进了精神分裂症研究的转化方法，旨在确定基于病理生理学的新治疗干预目标，并开发可用于监测疗效的病理生理学生物标志物。 此类干预措施。因此，拟议的中心是一个多学科的努力，旨在测试机制假设，以提高我们对精神分裂症疾病过程核心组成部分的理解。此外，该中心提供 1) 丰富的培训和职业发展环境，使个人可以参与研究，利用基础神经科学的方法和知识库来解决临床精神分裂症研究中的关键问题，以及 2) 向更广泛的科学界和非专业界传播精神分裂症转化研究的重要性以及从中获得的知识。