Development of Cortical-Amygdala Interactions

皮质-杏仁核相互作用的发展

• 批准号: 7904165
• 负责人: FRANCISCO XAVIER CASTELLANOS
• 金额: $ 30.35万
• 依托单位: NATHAN S. KLINE INSTITUTE FOR PSYCH RES
• 依托单位国家: 美国
• 财政年份: 2009
• 资助国家: 美国
• 起止时间: 2009-08-01 至 2012-04-30
• 项目状态: 已结题
• 来源: https://reporter.nih.gov/project-details/7904165
• 关键词: Adolescence; Adolescent; Adult; Affect; Amygdaloid structure; Animal Model; Animals; Autoradiography; Brain; Brain Mapping; Brain imaging; Child; Child Abuse; Data; Deoxyglucose; Development; Environment; Exhibits; Experimental Models; Functional Imaging; Functional Magnetic Resonance Imaging; Glucose; Growth; Human; Image; Imaging Techniques; Infant; Intake; Learning; Life Experience; Link; Mental Depression; Modeling; Mood Disorders; Mothers; Neurobiology; Neurosciences; Phase; Prefrontal Cortex; Preparation; Rattus; Research Personnel; Scanning; Shock; Social Interaction; Sucrose; Swimming; Techniques; Testing; Time; Translations; Trauma; age related; analog; analytical method; depressive symptoms; experience; hemodynamics; imaging modality; improved; indexing; infancy; interest; juvenile animal; multidisciplinary; novel; postnatal; public health relevance; pup; response; young adult

DESCRIPTION (provided by applicant): Child abuse is associated with depression, although the emergence of depression is often delayed until adolescence or young adulthood. We propose to study an experimental model of active parental abuse that is associated with adolescent and adult manifestation of increased immobility time in a forced swim test model of depression. Specifically, infant rats receive an electric shock while interacting with their mother during a developmentally limited sensitive period that lasts until postnatal day 9. Our group found that compared to control rats (interacting with the mother without shock or shock without the mother); abusive attachment rats had significantly decreased amygdala size, disrupted social interactions with the mother, and enhanced amygdala 2-deoxy-glucose activity in infancy. However, methodological barriers have impeded the needed translation from this well documented and powerful model to our understanding of the neurobiology of abused and mood disordered children and adolescents. In this multidisciplinary application, we propose to bridge these domains by applying a novel fMRI technique that has been remarkably fruitful in revealing the developmental trajectories of human brain to developing rats. Specifically, we will map brain functional connectivity between prefrontal cortex and amygdala in weanling, adolescent, and young adult rats in which early life experiences have been experimentally manipulated. In the second phase of this R21/R33 application, we propose to extend our paradigm to pre-weanling rats. Attainment of our aims will dramatically accelerate the iterative development of the neuroscience of adverse early environments and their consequences on brain development. PUBLIC HEALTH RELEVANCE: Development of Cortical-Amygdala Interactions Project Narrative Child abuse is often associated with depression in adolescence or young adulthood. We propose to study an experimental model of parental abuse that is associated with giving up more rapidly in a forced swim test model of depression. Our multidisciplinary team of investigators proposes to apply a new brain imaging technique that is helping us to learn about brain development in children, by now using it to understand brain development in young lab rats. Being able to use the same techniques in children and lab animals will improve our ability to understand how brain development is affected by adverse early life experiences.

描述（由申请人提供）：虐待儿童与抑郁症有关，尽管抑郁症的出现通常延迟到青春期或成年。我们建议研究一种主动虐待父母虐待的实验模型，该模型与青少年和成人表现相关，在强迫游泳测试模型的抑郁症模型中固定时间增加。具体而言，婴儿大鼠在发育有限的敏感时期与母亲互动时会收到电击，持续到产后第9天。我们的小组发现，与对照大鼠相比（与母亲互动而没有母亲的情况下与母亲互动）；虐待依恋大鼠的大小显着降低了杏仁核的大小，与母亲的社交相互作用破坏了，并增强了婴儿期杏仁核2-脱氧葡萄糖活性。但是，方法论上的障碍阻碍了我们对虐待和情绪失调的儿童和青少年的神经生物学的理解，从而阻碍了所需的翻译。在这个多学科的应用中，我们建议通过应用一种新型的功能磁共振成像技术来弥合这些领域，该技术在揭示人脑的发育轨迹上对发育大鼠的发育轨迹非常有效。具体而言，我们将在断奶，青少年和年轻的成年大鼠中绘制前额叶皮层和杏仁核之间的大脑功能连通性，在这些大鼠中已经通过实验进行了早期生活经历。在此R21/R33应用程序的第二阶段，我们建议将范式扩展到预性大鼠。实现我们的目标将极大地加速不良早期环境神经科学的迭代发展及其对大脑发育的影响。 公共卫生相关性：皮质 - 杏仁核相互作用的发展项目叙事虐待儿童通常与青春期或成年后的抑郁症有关。我们建议研究一种父母虐待的实验模型，该模型与在强迫游泳测试模型中更快地放弃抑郁症。我们的多学科研究人员建议采用一种新的脑成像技术，该技术正在帮助我们了解儿童的大脑发育，现在使用它来了解年轻实验室大鼠的大脑发育。能够在儿童和实验室动物中使用相同的技术将提高我们了解大脑发育如何受到不良早期生活经历的影响的能力。