Resolving amygdala microcircuits: implications for function

分解杏仁核微电路：对功能的影响 多年来对人类精神疾病，包括高危人群的神经成像研究，强调了涉及杏仁核的回路的变化。特定皮质和杏仁核相关活动的“指纹”有望帮助识别与特定疾病相关的特定回路。尽管如此，大脑皮质-杏仁核环路的结构或“连接”细节仍不清楚。在这里，我们研究了这样一种想法，即不同种类的疾病的独特症状特征可以通过不同的皮质输入组合如何在杏仁核形成“微电路”来最好地解释，每个微电路都与独特的输出路径相关。这项建议侧重于投射到杏仁核的皮质结节，并且经常涉及精神疾病。膝下扣带回前部(SgACC)和头端无颗粒脑岛(Ia)调节身体内部感觉或“感觉间状态”；膝周前扣带回(PgACC)和中间颗粒异常脑岛(ID)是参与“社会监控”和联系反应的区域。利用同一动物的双重顺行追踪方法，我们的初步数据显示，来自pgACC“社会监测”节点的传入终末总是“嵌套”在从杏仁核的sgACC(“相互感觉”)到达的终末中。sgACC终末覆盖的区域更广。这种重叠形成了sgACC和pgACC传入整合的终末“热点”。在细胞水平上，sgACC和pgACC相关的终末几乎总是共接触锥体细胞(而不是分离到不同的群体)，并且这一比例非常稳定。这些数据表明，正常的、严格的传入控制，以及传入信息整合到这些“热点”的杏仁核神经元上。这种末端平衡表明，在不同的疾病状态下，解剖底物可能会发生变化。我们还发现，在汇聚的sgACC/pgACC热点区域，杏仁核神经元有明显的返回皮质的投射，这与非热点区域不同。在这个提案中，我们剖析了涉及sgACC、Ia、pgACC和ID的微电路。我们首先确定涉及这些节点的特定皮质网络(目标1)，然后研究来自不同两个节点系统的传入终末如何在杏仁核重叠或分离，包括在细胞水平上(目标2A，B)。然后，我们检查汇聚的传入“热点”中的杏仁核神经元是否有独特的输出到皮质(目标3)。

Resolving amygdala microcircuits: implications for function Years of neuroimaging research in human psychiatric disorders, including at-risk populations, highlights alterations in circuits involving the amygdala. 'Fingerprints' of specific cortical and amygdala correlated activity promise to help identify specific circuits involved in particular diseases. Despite this, the structural or 'wiring' details of cortical-amygdala circuits remain obscure. Here we examine the idea that the unique symptom profiles across heterogeneous disorders are best explained by how different combinations of cortical inputs form 'microcircuits' in the amygdala, each associated with unique output paths. This proposal focuses on cortical nodes that project to the amygdala, and are frequently involved in psychiatric conditions. The subgenual anterior cingulate (sgACC) and rostral agranular insula (Ia) mediate internal body sensations, or 'interoceptive states'; the perigenual ACC (pgACC) and the middle, dysgranular insula (Id) are regions involved in 'social monitoring' and affiliative responses. Using dual anterograde tract tracing approaches in the same animal, our preliminary data show that afferent terminals from pgACC 'social monitoring' nodes are always 'nested' in terminals arriving from the sgACC ('interoceptive) in the amygdala. sgACC terminals cover a broader territory. This overlap creates terminal 'hotspots' of sgACC and pgACC afferent integration. At the cellular level, sgACC and pgACC associated terminals almost always co-contacted pyramidal cells (rather than segregating to different populations), and did so in a very stable ratio. These data indicate normal, tight afferent control, and integration of incoming information, onto amygdala neurons in these 'hotspots'. This terminal balance suggests an anatomic substrate that may be altered in various disease states. We also found that amygdala neurons in converging sgACC/pgACC hotspots had distinct projections back to the cortex, which were different than from non-hotspots regions. In this proposal, we dissect microcircuits involving sgACC, Ia, pgACC, and Id. We begin with determining specific cortical networks involving these nodes (Aim 1), then examine how afferent terminals from different two-node systems overlap or segregate in the amygdala, including at the cellular level (Aim 2A, B). We then examine whether amygdala neurons in converging afferent 'hotspots' have unique outputs to the cortex (Aim 3).