Neural Transplantation within Amygdalar Circuitry

杏仁核回路内的神经移植

• 批准号: 7018317
• 负责人: Miles Gregory Cunningham
• 金额: $ 15万
• 依托单位: MCLEAN HOSPITAL
• 依托单位国家: 美国
• 财政年份: 2006
• 资助国家: 美国
• 起止时间: 2006-05-05 至 2011-04-30
• 项目状态: 已结题
• 来源: https://reporter.nih.gov/project-details/7018317
• 关键词: amygdala; anxiety; anxiety disorders; biological models; cell transplantation; electron microscopy; embryo /fetus tissue /cell culture; emotions; fear; gamma aminobutyrate; genetically modified animals; immunocytochemistry; laboratory mouse; laboratory rat; laser capture microdissection; microdialysis; molecular biology; nervous system transplantation; neurons; neuropsychology; nonhuman therapy evaluation; stereotaxic techniques; therapy design /development

DESCRIPTION (provided by applicant): The present application proposes that strategic engraftment of specific cell types within the corticolimbic system is a potential new method for modifying or reconstructing emotional circuitry. Having earned a PhD from MIT and an MD from Harvard Medical School, I completed my psychiatry residency in 2001 at the Massachusetts General Hospital. I have worked with Dr. Francine Benes as a post-doc through residency training, and she has agreed to mentor this proposal. McLean Hospital has committed to providing full access to the Mailman Research Center, complete with an approved animal colony, cell culture facilities, microscopy and imaging systems, and a center for electron and confocal microscopy. My immediate goals are to augment my skills while constructing a collaborative laboratory capable of applying diverse methods to address complex questions in neuroscience. My long-term goal is to develop as a physician-scientist capable of employing diverse approaches to investigate mental illness. During the 5-year grant period, I will attend courses and receive individualized instruction from faculty at this institution to strengthen my abilities in designing and implementing experiments, employing behavioral and molecular techniques, and using multivariate statistics to analyze complex data. These skills will be learned in the context of a series of experiments designed to investigate the potential for introducing cellular components into the corticolimbic system, thereby "biologically altering" circuitry associated with emotions. Cell suspensions rich in GABAergic neurons will be placed within the amygdala, and behavioral models will be used to assess the influence of these grafts on fear and anxiety. Transplanted cells will be evaluated for survival and functional integration using microdialysis, immunohistochemistry, EM, and molecular biological techniques. Preliminary results support the hypothesis that GABAergic neurons can survive after transplantation and increase inhibitory tone, thereby attenuating the fear response. Fear and anxiety are major components of the vast majority of psychiatric syndromes; and anxiety disorders, in their own right, are more prevalent than any other mental illness. This proposal may provide new insights into the treatment of these pervasive conditions, as it presents a novel approach to the study of the cellular and molecular function of the fear response.

描述（由申请人提供）：本申请提出，皮质边缘系统内特定细胞类型的策略性移植是用于修改或重建情绪回路的潜在新方法。我在麻省理工学院获得博士学位，在哈佛医学院获得医学博士学位。2001年，我在马萨诸塞州总医院完成了精神病学住院医师实习。我曾与弗朗辛·贝尼斯博士合作，作为博士后进行住院医师培训，她同意指导这项提案。姆克林医院已承诺提供完全访问梅尔曼研究中心，完成批准的动物群体，细胞培养设施，显微镜和成像系统，以及电子和共聚焦显微镜中心。我的近期目标是增强我的技能，同时建立一个能够应用不同方法来解决神经科学中复杂问题的协作实验室。我的长期目标是发展成为一名能够采用多种方法来研究精神疾病的医生科学家。在5年的资助期内，我将参加课程，并接受该机构教师的个性化指导，以加强我在设计和实施实验，采用行为和分子技术以及使用多元统计分析复杂数据方面的能力。这些技能将在一系列实验的背景下学习，这些实验旨在研究将细胞成分引入皮质边缘系统的潜力，从而“生物学上改变”与情绪相关的电路。富含GABA能神经元的细胞悬浮液将被放置在杏仁核内，行为模型将用于评估这些移植物对恐惧和焦虑的影响。将使用微透析、免疫组织化学、EM和分子生物学技术评价移植细胞的存活和功能整合。初步结果支持这一假设，即GABA能神经元可以在移植后存活，并增加抑制音，从而减弱恐惧反应。恐惧和焦虑是绝大多数精神病综合征的主要组成部分;焦虑症本身比任何其他精神疾病都更普遍。这一提议可能为治疗这些普遍性疾病提供新的见解，因为它为研究恐惧反应的细胞和分子功能提供了一种新的方法。