Inhibition, Oscillations and Information Processing in Schizophrenia

这个康特精神疾病神经科学中心(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、艺术与科学学院和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代表了横跨分子、系统、认知、计算和临床神经科学的广泛专业知识，提供了补充方法来检验中心假设，即GABA神经元亚群(病理学)中独特的分子变化模式会导致皮层网络振荡(病理生理学)中的保守障碍，而皮质网络振荡(病理生理学)是精神分裂症核心信息处理缺陷(临床综合征)的基础。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神经元不同亚群中的分子异常(项目1-Lewis)；2)综合计算、电生理学和解剖学方法确定特定细胞类型的皮质GABA神经传递与体外振荡之间的关系(项目2-Ermentrout)；3)GABA神经传递在任务引发的皮质振荡中的作用，该任务在非人类灵长类动物中触发与精神分裂症相同的信息处理域(项目3-Olson)；4)精神分裂症患者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)；以及5)开发新的PET成像工具，用于研究活体人类皮质GABA神经元的功能(项目5-Mathis)。这些项目的协同作用和双向互动促进了精神分裂症研究的翻译方法，旨在为新的治疗干预确定基于病理生理学的靶点，并开发可用于监测 这样的干预。因此，拟议的中心是一个多学科的努力，旨在测试一个机械论的假设，以提高我们对精神分裂症疾病过程的核心组成部分的理解。此外，该中心提供了1)丰富的培训和职业发展环境，个人可以参与研究，利用基础神经科学的方法和知识基础来解决临床精神分裂症研究中的关键问题，以及2)机制 向更广泛的科学界和非科学界传播精神分裂症翻译研究的重要性和所获得的知识。

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.