Characterizing a Circuit Linking Auditory Cortical Systems and the Social Behavior Network

表征连接听觉皮层系统和社会行为网络的电路

• 批准号: 10058205
• 负责人: Jeremy Spool
• 金额: $ 6.64万
• 依托单位: UNIVERSITY OF MASSACHUSETTS AMHERST
• 依托单位国家: 美国
• 财政年份: 2019
• 资助国家: 美国
• 起止时间: 2019-11-01 至 2022-10-31
• 项目状态: 已结题
• 来源: https://reporter.nih.gov/project-details/10058205
• 关键词: Aggressive behavior; Animals; Auditory; Auditory area; Auditory system; Birds; Brain; Brain region; Cell Nucleus; Communication; Complex; Cues; Data; Decision Making; Disease; Disease model; Exhibits; Foundations; Frontotemporal Dementia; Goals; Hearing; Human; Immediate-Early Genes; Impairment; Knowledge; Label; Laboratories; Lead; Learning; Link; Mammals; Measurement; Medial; Modality; Modeling; Neurologic Symptoms; Neurons; Neurosciences; Neurosciences Research; Olfactory Pathways; Outcome; Output; Partner in relationship; Pathway interactions; Play; Process; Production; Reproduction; Research; Secondary Lesion; Sensory; Signal Transduction; Social Behavior; Social Environment; Social Functioning; Social Interaction; Songbirds; Stimulus; Symptoms; Synapses; System; Testing; Therapeutic Intervention; Time; Training; Variant; Vertebrates; Visual; Work; autism spectrum disorder; base; behavior influence; diencephalon; improved; insight; nervous system disorder; novel; novel strategies; optogenetics; preference; programs; relating to nervous system; response; sensory cortex; sensory system; social; social communication; sound; success; therapeutic target; vocalization; zebra finch

PROJECT SUMMARY/ABSTRACT To engage in productive social interactions, the brain must coordinate processing of complex social sensory cues with production of appropriate social responses. Deficits in appropriate responses to social sensory cues are a feature of several prevalent neurological disorders, including frontotemporal dementia and autism spectrum disorders. While complex social signals (i.e., visual, auditory) are processed in cortex, nuclei controlling social behaviors (conserved across vertebrates), called the social behavior network (SBN), lie mainly in the diencephalon. Tremendous progress has been made in studying cortical sensory circuits and the SBN separately but apart from mammalian olfactory systems we are lacking basic knowledge of how information is coordinated between sensory cortex and SBN circuits. These connections are very likely to be critical for productive social interactions. The long-term goal of this training proposal is to characterize components of a circuit connecting auditory cortical regions with SBN nuclei. This research will be carried out in songbirds (specifically, Zebra finches; Taeniopygia guttata), which are ideal for realizing the proposal's long- term goal. Zebra finches learn and employ complex vocalizations in a rich variety of social contexts. In songbirds, complex social vocalizations induce immediate early gene labeling in both secondary auditory cortical regions and SBN nuclei. Lesions of secondary auditory cortex impair vocal recognition and mate preference, suggesting that cortical inputs to social nuclei play key roles in social decision-making. I have gathered preliminary data showing that secondary auditory cortical regions send projections to a region of the avian cortex, the medial arcopallium, and previous data demonstrate the medial arcopallium sends projections to several SBN nuclei. Based on these findings, this proposal hypothesizes that cortical auditory regions provide SBN nuclei with social-auditory input in part through this arcopallial region of the songbird cortex to influence behavioral decisions. The specific aims of my proposal will characterize this circuit through 1) testing how inactivation of auditory cortical regions during playback of social vocalizations alters immediate early gene measurements across SBN nuclei, 2) optogenetically identifying and stimulating synaptic connections between auditory cortex and the medial arcopallium, and 3) testing selectivity of medial arcopallial neurons for auditory- social stimuli in freely moving animals. This proposal will be the first to characterize an auditory cortical -> SBN circuit in vertebrates by bridging progress made in auditory systems neuroscience and research in the neural basis of social behavior. Deficits in social sensory cue processing and the ability to engage in social behavior are features of several neurological disorders. The findings generated by this proposal will open up new avenues for research on this vital function by expanding basic knowledge of coordination between cortical sensory circuits and social behavior nuclei.

项目概要/摘要 为了进行富有成效的社交互动，大脑必须协调复杂的社交感官的处理 产生适当的社会反应的线索。对社会感官线索的适当反应存在缺陷 是几种常见神经系统疾病的一个特征，包括额颞叶痴呆和自闭症 频谱障碍。虽然复杂的社交信号（即视觉、听觉）是在皮层、核中处理的 控制社会行为（在脊椎动物中保守），称为社会行为网络（SBN），谎言 主要分布于间脑。皮层感觉回路和神经网络的研究取得了巨大进展 SBN 是分开的，但除了哺乳动物的嗅觉系统之外，我们缺乏关于如何进行 SBN 的基本知识 信息在感觉皮层和 SBN 电路之间进行协调。这些连接很可能是 对于富有成效的社交互动至关重要。该培训计划的长期目标是表征 连接听觉皮层区域和 SBN 核的电路的组成部分。这项研究将进行 在鸣禽（特别是斑胸草雀；Taeniopygia guttata）中，这是实现该提案长期目标的理想选择 术语目标。斑胸草雀在丰富多样的社会环境中学习和运用复杂的发声。在 对于鸣禽来说，复杂的社会发声会在次级听觉中立即诱导早期基因标记 皮质区域和 SBN 核。次级听觉皮层损伤会损害声音识别和交配 偏好，表明皮质对社会核的输入在社会决策中发挥着关键作用。我有 收集到的初步数据表明，次级听觉皮层区域将投射发送到听觉皮层的某个区域。 鸟类皮质、内侧弧皮质和之前的数据表明内侧弧皮质发送投射 到几个SBN核。基于这些发现，该提议假设皮质听觉区域 部分通过鸣禽皮层的这个arcopalial区域为SBN核提供社会听觉输入 影响行为决策。我的提案的具体目标将通过 1) 测试来表征该电路 回放社交发声过程中听觉皮层区域的失活如何改变即早基因 跨 SBN 核的测量，2) 光遗传学识别和刺激之间的突触连接 听觉皮层和内侧弧皮质，以及 3) 测试内侧弧皮质神经元对听觉的选择性 自由活动的动物的社会刺激。该提案将是第一个描述听觉皮层 -> SBN 特征的提案 通过连接听觉系统神经科学和神经系统研究的进展，在脊椎动物中建立电路 社会行为的基础。社交感官线索处理和参与社交行为的能力存在缺陷 是多种神经系统疾病的特征。该提案产生的调查结果将开辟新的 通过扩展皮层之间协调的基础知识，研究这一重要功能的途径 感觉回路和社会行为核。