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).

解析杏仁核微回路：对功能的影响 多年来对人类精神疾病（包括高危人群）的神经影像学研究突出了涉及杏仁核的回路的改变。特定皮层和杏仁核相关活动的“指纹”有望帮助识别与特定疾病有关的特定回路。尽管如此，皮质-杏仁核回路的结构或“布线”细节仍然不清楚。在这里，我们研究的想法，跨异质性疾病的独特的症状配置文件是最好的解释，如何不同的组合皮层输入形式的“微电路”在杏仁核，每个与独特的输出路径。这个建议集中在皮质节点，项目到杏仁核，并经常涉及精神疾病。膝下前扣带回（sgACC）和吻侧无颗粒岛叶（Ia）介导内部身体感觉或“内感受状态”;膝周扣带回（pgACC）和中间颗粒异常岛叶（Id）是参与“社会监测”和亲和反应的区域。在同一动物中使用双顺行道追踪方法，我们的初步数据表明，从pgACC的“社会监测”节点的传入终端总是“嵌套”在终端到达从杏仁核中的sgACC（“interoceptive”）。sgACC终端覆盖的领域更广。这种重叠产生了sgACC和pgACC传入整合的末端“热点”。在细胞水平，sgACC和pgACC相关的终端几乎总是共同接触锥体细胞（而不是分离到不同的群体），并以非常稳定的比例这样做。这些数据表明，正常的，严格的传入控制，并整合传入信息，到杏仁核神经元在这些“热点”。这种终末平衡表明，在各种疾病状态下，可能会改变解剖基质。我们还发现，杏仁核神经元在会聚sgACC/pgACC热点有明显的投射回皮层，这是不同于非热点地区。在这个提议中，我们解剖涉及sgACC，Ia，pgACC，和Id的微电路。我们开始确定特定的皮质网络涉及这些节点（目标1），然后检查如何传入终端从不同的两个节点系统的重叠或分离在杏仁核，包括在细胞水平（目标2A，B）。然后，我们研究是否杏仁核神经元在收敛传入的“热点”有独特的输出到皮层（目的3）。