Identification of Cell Type-Specific Actions of Antipsychotic Drugs

描述（由申请人提供）：精神分裂症是最令人衰弱的精神疾病之一，影响全球约1%的人口。许多抗精神病药物是可用的，但这些药物往往是无效的，不能治疗疾病的所有症状。新的治疗方法是必要的，但他们的发现已经阻碍了有限的理解这种复杂的神经系统疾病的病因，并缺乏明确的了解，可用的抗精神病药物的作用的精确分子机制。确定抗精神病药物作用的分子机制的主要限制之一是中枢神经系统的异质性和混杂细胞的性质。因此，Conte中心拟议研究的主要目标是通过创新方法全面了解抗精神病药物的细胞和分子作用，这些方法使用新型啮齿动物模型来分析皮质-纹状体回路内的各种类型的神经元。项目1的中心主任和领导人是保罗·格林加德（洛克菲勒大学）。其他项目负责人是：Nathaniel Heintz（洛克菲勒大学项目2）;安格斯Nairn（耶鲁大学项目3）; Eric Nestler（西奈山医学院项目4）;和James Surmeier（西北大学项目5）。还将有一个动物核心，一个分子和生化试剂核心，和一个行政核心。参与研究的五位私人研究员在过去曾进行有效的合作，并会利用他们互补的专业知识和资源，以跨学科的方法进行拟议的研究。通过使用生物化学，细胞生物学，分子，电生理，结构和行为分析，拟议的康特中心将实现抗精神病药物在皮质纹状体电路的细胞和分子作用的更全面的了解。 公共卫生相关性：与公共卫生的相关性：精神分裂症是一种使人衰弱的精神疾病，需要新的治疗方法。该中心将描述抗精神病药物对精神分裂症中涉及的特定神经元亚型的特性的影响，从而全面了解这些药物的正常和适应不良作用，并导致更好的治疗，具有更高的疗效和更少的副作用。

DESCRIPTION (provided by applicant): Schizophrenia is one of the most debilitating psychiatric disorders, affecting approximately 1% of the population worldwide. A number of antipsychotic drugs are available but these are often ineffective and do not treat all the symptoms of the disease. New therapeutics are needed but their discovery has been hampered by a limited understanding of the etiology of this complex neurological disorder, and a lack of clear understanding of the precise molecular mechanisms of action of available antipsychotic drugs. One of the major limitations in identifying the molecular mechanisms of antipsychotic drug action has been the heterogeneous and intermixed cellular nature of the central nervous system. The major goal of the proposed studies in the Conte Center is therefore to achieve a complete understanding of the cellular and molecular actions of antipsychotic drugs through innovative approaches that use novel rodent animal models to allow analysis of individual types of neurons within cortico-striatal circuits. The Center Director and leader of Project 1 is Paul Greengard (Rockefeller University). The other Project leaders are: Nathaniel Heintz (Project 2, Rockefeller University); Angus Nairn (Project 3, Yale University); Eric Nestler (Project 4, Mount Sinai Medical School); and James Surmeier (Project 5, Northwestern University. There will also be an Animal Core, a Molecular & Biochemical Reagents Core, and an Administrative Core. The five Pis involved have an established history of effective collaboration and will use their complementary expertise and resources to take a multi-disciplinary approach in the proposed research. Through the use of biochemical, cell biological, molecular, electrophysiological, structural and behavioral assays, the proposed Conte Center will achieve a fuller understanding of the cellular and molecular actions of antipsychotic drugs in the cortico-striatal circuits. PUBLIC HEALTH RELEVANCE: Relevance to public health: Schizophrenia is a debilitating psychiatric disorder, and new therapies are needed. This Conte Center will characterize the effects of antipsychotic drugs on the properties of specific neuronal subtypes involved in schizophrenia, allowing for a complete understanding of the normal and maladaptive actions of these drugs, and leading to better therapies with higher efficacy and fewer side-effects.