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会延迟到青春期或成年初期。我们建议研究一种主动父母虐待的实验模型，该模型与抑郁症强迫游泳测试模型中青少年和成人不动时间增加的表现相关。具体来说，幼鼠在发育受限的敏感期（持续到出生后第 9 天）与母亲互动时会受到电击。我们的研究小组发现，与对照大鼠（在没有电击的情况下与母亲互动或没有母亲的情况下电击）相比；虐待性依恋大鼠的杏仁核大小显着减小，与母亲的社交互动受到干扰，并且婴儿期杏仁核 2-脱氧葡萄糖活性增强。然而，方法上的障碍阻碍了将这个有据可查且强大的模型转化为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。在这个多学科应用中，我们建议通过应用一种新颖的功能磁共振成像技术来弥合这些领域，该技术在揭示人类大脑向发育中的老鼠的发育轨迹方面取得了显着的成果。具体来说，我们将绘制断奶大鼠、青少年大鼠和年轻成年大鼠的前额皮质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。我们目标的实现将极大地加速不良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.