Resolving amygdala microcircuits: implications for function

解析杏仁核微电路：对功能的影响

• 批准号: 10501552
• 负责人: JULIE L. FUDGE
• 金额: $ 62.56万
• 依托单位: UNIVERSITY OF ROCHESTER
• 依托单位国家: 美国
• 财政年份: 2022
• 资助国家: 美国
• 起止时间: 2022-08-12 至 2027-05-31
• 项目状态: 未结题
• 来源: https://reporter.nih.gov/project-details/10501552
• 关键词: Amygdaloid structure; Anatomic Models; Anatomy; Animals; Anterior; Area; Back; Brain; Cells; Cercopithecidae; Conflict (Psychology); Cues; Data; Development; Disease; Emotional; Equilibrium; Esthesia; Feedback; Fingerprint; Functional disorder; Glutamates; Goals; Heart; Human; Injections; Insula of Reil; Intercept; Label; Maps; Mediating; Mental disorders; Monitor; Monkeys; Neurons; Output; Pain; Perception; Population; Populations at Risk; Primates; Pyramidal Cells; Research; Source; Symptoms; System; Visceral; Work; associated symptom; behavioral outcome; design; experimental study; human model; information processing; neuroimaging; response; social; social communication

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).

解决杏仁核微电路：对功能的影响 包括高危人群在内的人类精神疾病的多年神经影像研究突出了涉及杏仁核的电路的变化。特定皮质和杏仁核相关的活动的“指纹”有望帮助确定与特定疾病有关的特定电路。尽管如此，皮质 - 杏仁核电路的结构或“接线”细节仍然晦涩难懂。在这里，我们研究了以下想法：在杏仁核中如何形成皮质输入的不同组合，可以很好地解释跨异质性疾病的独特症状特征，每种皮质输入的组合如何与独特的输出路径相关联。该提案的重点是向杏仁核投射的皮质节点，并经常参与精神病疾病。亚果位前扣带回（SGACC）和tho骨granular insula（IA）介导体内感觉或“互感状态”；阴性ACC（PGACC）和中间的差裂（ID）是参与“社会监测”和从属反应的区域。我们的初步数据使用同一动物中的​​双重顺行迹追踪方法，表明，来自PGACC“社交监测”节点的传入终端总是在从SGACC（'Interoctive）到杏仁核中的SGACC（“ Interoptive）到达的终端中”。 SGACC航站楼涵盖了更广阔的领域。这种重叠创建了SGACC和PGACC传入集成的终端“热点”。在细胞水平上，SGACC和PGACC相关的末端几乎总是共同接触的锥体细胞（而不是隔离到不同种群），并且以非常稳定的比率进行。这些数据表明在这些“热点”中，正常，紧密的传入控制以及传入信息的整合到杏仁核神经元上。这种最终平衡表明在各种疾病状态下可能会改变的解剖基质。我们还发现，收敛的SGACC/PGACC热点中的杏仁核神经元具有不同的投影回到皮层，这与非螺柱区域不同。在此提案中，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（AIM 1），然后检查来自不同两个节点系统的传入终端如何重叠或在杏仁核中分离，包括在细胞级别（AIM 2A，B）。然后，我们检查杏仁核神经元在收敛传入的“热点”中是否具有对皮质的独特输出（AIM 3）。