Development of Cortical-Amygdala Interactions

描述（由申请人提供）：儿童虐待与抑郁症有关，尽管抑郁症的出现通常延迟到青春期或青年期。我们建议研究一个主动父母虐待的实验模型，该模型与青少年和成人在抑郁症的强迫游泳测试模型中增加不动时间的表现有关。具体来说，在发育受限的敏感期，幼鼠在与母亲互动时受到电击，这一敏感期一直持续到出生后第9天。我们的研究小组发现，与对照大鼠（与母亲互动而不受电击或在没有母亲的情况下受到电击）相比；虐待依恋大鼠在婴儿期杏仁核大小明显减小，与母亲的社会互动中断，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充分记录和强大的模型到我们对受虐待和情绪障碍儿童和青少年的神经生物学的理解所需的翻译。在这个多学科的应用中，我们建议通过应用一种新的功能磁共振成像技术来弥合这些领域，该技术在向发育中的大鼠揭示人类大脑的发育轨迹方面取得了显著成果。具体来说，我们将绘制断奶大鼠、青春期大鼠和年轻成年大鼠前额叶皮层和杏仁核之间的大脑功能连接图，这些大鼠的早期生活经历已被实验操纵。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的大鼠。实现我们的目标将极大地加速神经科学的迭代发展，研究不良的早期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.