Development of Cortical-Amygdala Interactions

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推迟到青春期或成年早期。我们建议研究一个实验模型，积极的父母虐待，与青少年和成人表现的不动时间增加强迫游泳测试模型抑郁症。具体来说，幼鼠在与其母亲互动的过程中接受电击，这一过程持续到出生后第9天。我们的研究小组发现，与对照组大鼠（与母亲互动而不休克或休克而不母亲）相比，虐待型依恋大鼠的杏仁核大小显著减小，与母亲的社会互动中断，婴儿期杏仁核2-脱氧葡萄糖活性增强。然而，方法上的障碍阻碍了从这个有据可查的和强大的模型到我们对虐待和情绪障碍儿童和青少年的神经生物学的理解的必要翻译。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成像技术，在揭示人类大脑发育轨迹的发展中大鼠已经显着富有成效的桥梁这些领域。具体来说，我们将绘制大脑功能之间的连接，前额叶皮层和杏仁核在断奶，青春期和年轻的成年大鼠，其中早期的生活经验已被实验操纵。在R21/R33应用的第二阶段，我们建议将我们的范例扩展到断奶前大鼠。我们的目标的实现将极大地加速神经科学的迭代发展，即早期不利环境及其对大脑发育的影响。

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.