Development of Cortical-Amygdala Interactions

描述(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会推迟到青春期或成年后才出现。我们建议研究一种积极父母虐待的实验模型，该模型与青少年和成人在强迫游泳测试抑郁症模型中表现出的不动时间增加有关。具体地说，幼鼠在发育受限的敏感期与母亲互动时会受到电击，敏感期一直持续到出生后第9天。我们的团队发现，与对照组大鼠(与母亲互动而不受电击或没有母亲电击)相比，虐待依恋大鼠在婴儿时期显著缩小了杏仁核大小，扰乱了与母亲的社交互动，并增强了杏仁核2-脱氧葡萄糖的活性。然而，方法论障碍阻碍了从这个有充分证据和强大的模型到我们对受虐和情绪障碍儿童和青少年的神经生物学的理解所需的转换。在这个多学科的应用中，我们建议通过应用一种新的功能磁共振技术来弥合这些领域，该技术在揭示人类大脑对发育中的大鼠的发育轨迹方面取得了显著的成果。具体地说，我们将绘制断奶、青少年和年轻成年大鼠的前额叶皮质和杏仁核之间的大脑功能连接图，在这些大鼠中，早期生活经验已被实验性地操纵。在R21/R33应用的第二阶段，我们建议将我们的范例扩展到早期断奶的大鼠。我们目标的实现将极大地加速不利早期环境及其对大脑发育影响的神经科学的迭代发展。

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.