Dopamine and individual differences in social communication

多巴胺与社交沟通的个体差异

• 批准号: 7989981
• 负责人: Lauren V Riters
• 金额: $ 25.53万
• 依托单位: UNIVERSITY OF WISCONSIN-MADISON
• 依托单位国家: 美国
• 财政年份: 2007
• 资助国家: 美国
• 起止时间: 2007-12-10 至 2012-11-30
• 项目状态: 已结题
• 来源: https://reporter.nih.gov/project-details/7989981
• 关键词: Address; Affect; Animals; Behavior; Biological; Biological Models; Birds; Brain; Brain region; Breeding; Catecholamines; Cell Nucleus; Clinical; Communication; Complex; Copulation; Data; Descriptor; Disease; Dopamine; Dopamine Agonists; Dopamine Receptor; Environment; European; Feedback; Female; Funding; Gene Proteins; Goals; Heart; Hormonal; Human; Immediate-Early Genes; Individual; Individual Differences; Intervention; Label; Laboratories; Learning; Lesion; Light; Link; Mental disorders; Modeling; Motivation; National Institute of Mental Health; Neurons; Neurotransmitters; Oxidopamine; Partner in relationship; Pathway interactions; Pharmacological Treatment; Play; Principal Investigator; Production; Property; Psychological reinforcement; Regulation; Research; Rewards; Role; Shapes; Site; Social Behavior; Social Environment; Social Interaction; Songbirds; Stimulus; Sturnus vulgaris; Suggestion; System; Taxon; Terminology; Testing; Time; Tyrosine 3-Monooxygenase; Variant; Ventral Tegmental Area; Work; autism spectrum disorder; base; behavior test; design; experience; hedonic; insight; interest; male; medial preoptic nucleus; neural circuit; neurochemistry; neuroregulation; pleasure; programs; relating to nervous system; research study; response; skills; social; social communication; social group; synthetic enzyme

DESCRIPTION (provided by applicant): Appropriate communication is at the heart of successful, healthy social interactions in humans. Deficits in social communication are a hallmark of several mental disorders, including autism spectrum disorders. Such disorders are characterized by extreme individual variability in the motivation to communicate, and in the ability to engage in socially appropriate communication, yet very little research has been devoted to understanding the neural bases of these issues. Songbirds provide an ideal model system in which to study brain mechanisms regulating appropriate social communication. In our model species we find the brain to differentially regulate communication in a context in which song is directed towards a female (goal-directed) versus song observed in large social groups (group-motivated). In past studies we find that some individuals communicate at high levels and others not at all. Associated with individual differences in communication are differences in activity within brain regions involved in motivation and reward. We have been able to motivate birds to communicate through pharmacological manipulations of dopamine receptors, suggesting dopamine as a candidate neurotransmitter system involved in stimulating communication in individuals that are not highly motivated to communicate. The experiments proposed here test the hypothesis that individual differences in context-appropriate communication are dependent upon dopamine activity within neural systems involved in motivation and reward. To test this hypothesis we will examine the effects of site-specific dopamine lesions (Aim 1) and site-specific dopamine receptor subtype manipulations (Aim 2) on communication within goal- directed and socially-motivated contexts in low- and high-communicating individuals. Neural circuits influenced by these manipulations will be examined after behavioral testing through examinations of markers of neuronal activity and other neurochemical markers. Comparisons will then be made of multiple dopaminergic markers in low- and high-communicators in both contexts to identify differences in the brain associated with natural individual variation in context-appropriate communication (Aim 3). The proposed research will identify manipulations that stimulate context-appropriate social interactions, which can be used in the design of clinical interventions in humans with deficits in the motivation to communicate. The proposed studies span from neurons, to neural circuits, to complex social behavior, integrate what is known about motivation with studies on communication, examine the influence of environment and social context on individuals displaying natural variation in behavior, and will provide treatment ideas for individuals with psychiatric disease. Deficits in social communication are a hallmark of several mental disorders, including autism spectrum disorders. Such disorders are characterized by extreme individual variability in the motivation to communicate, and in the ability to engage in socially appropriate communication. The proposed research will identify manipulations that stimulate context-appropriate social interactions, which can be used in the design of clinical interventions in humans with deficits in the motivation to communicate.

描述（由申请人提供）：适当的沟通是人类成功、健康的社交互动的核心。社交沟通缺陷是多种精神障碍的标志，包括自闭症谱系障碍。此类疾病的特点是沟通动机和进行适当社交沟通的能力存在极大的个体差异，但很少有研究致力于了解这些问题的神经基础。鸣禽提供了一个理想的模型系统，用于研究调节适当社交沟通的大脑机制。在我们的模型物种中，我们发现大脑在针对女性（目标导向）的歌曲与在大型社会群体中观察到的歌曲（群体动机）的背景下对交流进行差异化调节。在过去的研究中，我们发现有些人的沟通水平很高，而另一些人则根本没有。与沟通中的个体差异相关的是涉及动机和奖励的大脑区域的活动差异。我们已经能够通过多巴胺受体的药理学操作来激励鸟类进行交流，这表明多巴胺作为一种候选神经递质系统，参与刺激交流动机不高的个体的交流。这里提出的实验测试了这样的假设：情境适当的沟通中的个体差异取决于涉及动机和奖励的神经系统内的多巴胺活动。为了检验这一假设，我们将检查特定位点多巴胺损伤（目标 1）和特定位点多巴胺受体亚型操作（目标 2）对低沟通和高沟通个体在目标导向和社会动机环境中沟通的影响。在行为测试后，将通过检查神经元活动标记和其他神经化学标记来检查受这些操作影响的神经回路。然后，对两种情境中低沟通者和高沟通者的多个多巴胺能标记进行比较，以确定与情境适当沟通中的自然个体差异相关的大脑差异（目标 3）。拟议的研究将确定刺激适合情境的社交互动的操作，这些操作可用于设计针对沟通动机缺陷的人类的临床干预措施。拟议的研究涵盖从神经元到神经回路，再到复杂的社会行为，将已知的动机与沟通研究相结合，检查环境和社会背景对表现出行为自然变化的个体的影响，并将为患有精神疾病的个体提供治疗思路。社交沟通缺陷是多种精神障碍的标志，包括自闭症谱系障碍。此类疾病的特点是沟通动机和进行适当社交沟通的能力存在极大的个体差异。拟议的研究将确定刺激适合情境的社交互动的操作，这些操作可用于设计针对沟通动机缺陷的人类的临床干预措施。