A novel role for higher order auditory circuits: social group dynamics and descending pathways to the Social Behavior Network

项目概要/摘要 健康的社会群体生活在很大程度上依赖于处理复杂感官环境的能力。在几个 普遍存在的神经系统和神经精神疾病、社交互动缺陷常常与此相关 听觉回路的病理学。高级听觉回路的广泛损伤导致社会行为的改变。 尽管听觉认知和社会行为之间存在密切联系，但我们缺乏关于听觉认知和社会行为的基本知识 高级听觉回路如何影响社会群体动态。该提案的长期目标是提供 加强培训，使申请人能够建立高级听觉回路支持的机制 在行为和神经层面融入社会群体。该提案的目标将测试在多大程度上 通过调查高级听觉通路在复杂群体中的作用，它们对于社会群体生活至关重要 动力学及其神经回路输出到社会行为大脑区域。在K99阶段，目标1将测试 初级和次级听觉大脑皮层（尾内侧）之间的通路的具体损伤程度 nidoapllium，NCM）可以改变配对关系和小群体动物的接近和回避行为 社会群体的形成。初步数据表明，来自高级听觉的下行神经通路 区域改变社会行为核中的社会听觉处理，即外侧腹内侧核 下丘脑（VMHl）。因此，目标 2 将测试听觉电生理特征的程度 记忆（在社交互动中至关重要）表现为较高的听觉 NCM 与社交记忆 行为核VMHl。在指导阶段和完成上述目标时，申请人将 除了新颖的概念培训外，还接受实施病毒介导的遗传的综合培训 神经通路消融、复杂社会群体动态的自动行为分析、社交网络 分析和多位点体内电生理记录。在R00独立阶段，申请人将 利用这种培训来推进一项研究计划，该计划从单一大脑区域的研究扩展到 突触连接的网络，从个人行为到大型社会群体动态。目标 3 和 4 将 继续测试下降路径在融入大型社会群体的速度中的作用，以及 检验 VMHl 使用更高的听觉回路输入来评估竞争动机的假设（即，使 参与社交行为与非社交行为的决定）。该提案的创新方法来自于 系统神经科学、行为神经内分泌学的技术和概念进步的交叉点， 和行为生态学，使用高度群居的研究物种斑胸草雀，不断解剖复杂的 大型社会群体中的听觉环境。扩大机制的基础知识，通过这些机制，更高 听觉通路影响社会群体生活可以为未来的治疗设计提供重要基础 神经和神经精神疾病的社会症状。

Project Summary/Abstract Healthy social group living relies heavily on the ability to process complex sensory environments. In several prevalent neurological and neuropsychiatric disorders, deficits in social interactions are frequently associated with pathology in auditory circuits. Broad lesions of higher auditory circuits result in alterations in social behavior. Despite a strong connection between auditory cognition and social behavior, we lack basic knowledge about how higher auditory circuits influence social group dynamics. The long-term goal of this proposal is to provide enhanced training that will enable the applicant to establish mechanisms by which higher auditory circuits support integration into social groups at behavioral and neural levels. Aims in this proposal will test the extent to which higher auditory pathways are critical for social group living through investigation of their role in complex group dynamics and their neural circuit outputs to social behavior brain areas. In the K99 phase, Aim 1 will test the extent to which specific damage to the pathway between primary and secondary auditory pallium (caudomedial nidoapllium, NCM) modifies approach and avoidance behavior in pair bonds and small groups of animals during social group formation. Preliminary data demonstrate that descending neural pathways from higher auditory areas modify social auditory processing in a social behavior nucleus, the lateral ventromedial nucleus of the hypothalamus (VMHl). Thus, Aim 2 will test the extent to which electrophysiological signatures of auditory memory (which is critical during social interactions) are represented in higher auditory NCM versus social behavior nucleus VMHl. During the mentored phase and in completion of the above Aims, the applicant will receive, in addition to novel conceptual training, comprehensive training implementing viral-mediated genetic ablation of neural pathways, automated behavioral analysis of complex social group dynamics, social network analysis, and multi-site in vivo electrophysiological recordings. In the R00 independent phase, the applicant will leverage this training to advance a research program that expands from study of single brain regions to synaptically-connected networks, and from individual behavior to large social group dynamics. Aims 3 & 4 will move forward to test the roles of descending pathways in the speed of integration into large social groups, and test the hypothesis that VMHl uses higher auditory circuit input to evaluate competing motivations (i.e., make decisions to engage in social versus non-social behaviors). The innovative approach of this proposal comes from the intersection of technical and conceptual advances in systems neuroscience, behavioral neuroendocrinology, and behavioral ecology using a highly gregarious study species, zebra finches, that constantly dissect complex auditory environments in large social groups. Expanding basic knowledge of mechanisms by which higher auditory pathways impact social group living can provide a critical foundation for future design of treatments for social symptoms of neurological and neuropsychiatric disorders.