The therapeutic potential of the cerebellum in schizophrenia

小脑对精神分裂症的治疗潜力

• 批准号: 9091647
• 负责人: Krystal Lynn Parker
• 金额: $ 16.39万
• 依托单位: UNIVERSITY OF IOWA
• 依托单位国家: 美国
• 财政年份: 2015
• 资助国家: 美国
• 起止时间: 2015-06-16 至 2020-04-30
• 项目状态: 已结题
• 来源: https://reporter.nih.gov/project-details/9091647
• 关键词: Animal Model; Animals; Area; Attention; Attention deficit hyperactivity disorder; Autistic Disorder; Award; Behavior; Behavioral; Bipolar Disorder; Brain; Budgets; Cells; Cerebellar Diseases; Cerebellum; Clinical; Cognition; Cognitive; Cognitive deficits; Collaborations; Common Core; Confocal Microscopy; Consult; Data; Data Analyses; Deep Brain Stimulation; Dentate nucleus; Development; Disease; Doctor of Philosophy; Dopamine; Educational process of instructing; Ensure; Environment; Experimental Designs; Faculty; Fellowship; Functional disorder; Future; Glutamates; Goals; Grant; Grant Review; Health; Histology; Human; Immunohistochemistry; Impaired cognition; Impairment; Iowa; Knowledge; Laboratories; Laboratory Study; Learning; Learning Skill; Left; Liquid substance; Manuscripts; Medial; Mediating; Mental disorders; Mentored Research Scientist Development Award; Mentors; Methods; Neurobehavioral Manifestations; Neurologist; Neurology; Neurons; Neurosciences; Output; Pathway interactions; Patients; Pharmacology; Phenotype; Physiology; Population; Positioning Attribute; Post-Traumatic Stress Disorders; Prefrontal Cortex; Process; Protocols documentation; Research; Research Personnel; Resources; Risk; Rodent; Role; Schizophrenia; Scientist; Short-Term Memory; System; Task Performances; Techniques; Testing; Thalamic structure; Therapeutic; Time; TimeLine; Training; Translating; Universities; Visit; Work; advanced system; behavioral impairment; behavioral pharmacology; career; career development; clinically relevant; cognitive process; cognitive task; effective therapy; experience; frontal lobe; human disease; innovation; insight; interest; member; nervous system disorder; neural patterning; neurophysiology; neuropsychiatric disorder; neuropsychiatry; novel therapeutics; optical fiber; optogenetics; programs; research study; skills; stem; symposium; targeted treatment; time interval

 DESCRIPTION (provided by applicant): Candidate: Dr. Krystal Parker is a postdoctoral research scholar in the Department of Neurology at the University of Iowa. She has an outstanding systems neuroscience background with a PhD in cerebellar circuitry and clinical training in cerebellar involvement in neuropsychiatric illness. Her primary research interests involve investigating mechanisms to harness the cerebellum to treat cognitive dysfunction in neuropsychiatric illness. Career Development: This award will 1) ensure Dr. Parker finalizes training in advanced systems neuroscience techniques such as multisite neuronal recordings paired with optogenetics and 2) is poised to make a smooth transition to an independent scientist focused on developing new treatments for patients suffering cognitive abnormalities stemming from neurological and psychiatric disease. This proposal will optimally position Dr. Parker for an independent career translating insights on the functional role of basic cerebellar circuitry into therapies that could help patients with cognitive dysfunction. Research Strategy: There are currently no effective treatments for cognitive dysfunction in neuropsychiatric illness as the underlying mechanisms are unknown. Dr. Parker and the Narayanan laboratory study cognitive deficits using an interval timing task. This task is ideally suited to study the basic circuitry of cognition in schizophrenia as patients have reliable deficits, task performance depends on known prefrontal circuitry, and it can be investigated in animals displaying schizophrenia-like phenotypes. The cerebellum is essential for cognition and Dr. Parker's preliminary data show that it is also required for interval timing. In addition, the cerebellum and prefrontal cortex are both consistently dysfunctional in schizophrenia patients suffering from cognitive dysfunction. Dr. Parker's preliminary data recapitulates timing deficits with disruption f both brain areas in animal models. Her overall goal is to develop an independent laboratory that focuses on leveraging the cerebellar connections to the frontal cortex to develop novel therapies in schizophrenia. The proposed experiments combine cutting-edge techniques to test the hypothesis that the cerebellum modulates dysfunctional prefrontal circuits impaired in schizophrenia. We expect that insights from this research will guide future therapies for patients suffering from impaired cognition. Mentors and Consultants: For this proposal, Dr. Parker has identified a strong mentoring team. Her primary mentors will be Dr. Narayanan, an innovative systems neuroscientist and neurologist who will teach her techniques for optogenetics, neuronal ensemble recordings, and data analysis. In parallel, she will work with senior established mentor, Dr. William Talman, who will intensively mentor her in many of the career development aspects during her postdoctoral fellowship period but also in immunohistochemistry using confocal microscopy. Dr. John Freeman will informally consult with Dr. Parker in aspects of cerebellar dependent behavior, cerebellar neuronal recordings, and cerebellar histology. Dr. Parker recognizes her need for mentors in schizophrenia and has joined forces with Drs. Bita Moghaddam and Mikhail Pletnikov, experts in experimental protocols in animals that are potentially relevant to schizophrenia. She will visit their laboratories to learn their methods, be immersed in their research programs, and discuss her results and experimental designs with them and their lab members. Environment: The University of Iowa boasts an exceptional research environment with leaders in neuropsychiatric research. In addition, the Department of Neurology strongly supports the candidate and will provide all the resources necessary for Dr. Parker to complete her proposed experiments and facilitate her transition to independence.

 描述（由申请人提供）： 候选人：Krystal Parker 博士是爱荷华大学神经病学系的博士后研究学者。她拥有出色的系统神经科学背景，拥有小脑回路博士学位以及小脑参与神经精神疾病的临床培训。她的主要研究兴趣包括研究利用小脑治疗神经精神疾病认知功能障碍的机制。职业发展：该奖项将 1) 确保 Parker 博士完成先进系统神经科学技术的培训，例如与光遗传学相结合的多位点神经元记录，2) 准备顺利过渡为独立科学家，专注于为因神经和精神疾病而患有认知异常的患者开发新的治疗方法。该提案将为帕克博士的独立职业提供最佳定位，将基本小脑回路功能作用的见解转化为可以帮助认知功能障碍患者的疗法。研究策略：由于潜在机制尚不清楚，目前尚无针对神经精神疾病认知功能障碍的有效治疗方法。帕克博士和纳拉亚南实验室使用间隔计时任务来研究认知缺陷。这项任务非常适合研究精神分裂症的认知基本回路，因为患者有可靠的缺陷，任务表现取决于已知的前额叶回路，并且可以在表现出精神分裂症样表型的动物中进行研究。小脑对于认知至关重要，帕克博士的初步数据表明，小脑对于间隔计时也是必需的。此外，小脑和 在患有认知功能障碍的精神分裂症患者中，前额皮质始终存在功能障碍。帕克博士的初步数据概括了动物模型中两个大脑区域受到破坏的时间缺陷。她的总体目标是建立一个独立的实验室，专注于利用小脑与额叶皮层的连接来开发精神分裂症的新疗法。所提出的实验结合了尖端技术来检验小脑调节精神分裂症中功能失调的前额叶回路的假设。我们期望这项研究的见解将为认知受损患者的未来治疗提供指导。导师和顾问：对于这个提案，帕克博士已经确定了一个强大的指导团队。她的主要导师是 Narayanan 博士，他是一位创新系统神经科学家和神经学家，将教授她光遗传学、神经元集成记录和数据分析技术。与此同时，她将与资深导师 William Talman 博士一起工作，后者将在博士后研究期间对她的许多职业发展方面以及使用共聚焦显微镜的免疫组织化学方面进行深入指导。约翰·弗里曼博士将在小脑依赖性行为、小脑神经元记录和小脑组织学方面与帕克博士进行非正式磋商。帕克博士认识到她在精神分裂症方面需要导师，并与帕克博士联手。 Bita Moghaddam 和 Mikhail Pletnikov 是研究可能与精神分裂症相关的动物实验方案的专家。她将参观他们的实验室，学习他们的方法， 沉浸在他们的研究项目中，并与他们及其实验室成员讨论她的结果和实验设计。环境：爱荷华大学拥有卓越的研究环境，拥有神经精神病学研究的领导者。此外，神经内科强烈支持候选人，并将为帕克博士提供所有必要的资源，以完成她提出的实验并促进她过渡到独立。