Dopamine and individual differences in social communication

描述（由申请人提供）：适当的沟通是人类成功、健康的社会互动的核心。社会沟通障碍是包括自闭症谱系障碍在内的几种精神障碍的标志。这类障碍的特点是在交流动机和参与社交适当交流的能力方面存在极端的个体差异，但很少有研究致力于理解这些问题的神经基础。鸣禽提供了一个理想的模型系统来研究调节适当的社会交流的大脑机制。在我们的模型物种中，我们发现大脑在针对雌性（目标导向）和大型社会群体（群体动机）的情况下调节交流的方式是不同的。在过去的研究中，我们发现有些人的沟通水平很高，而有些人则完全没有。与个体交流差异相关的是大脑中涉及动机和奖励的区域活动的差异。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，这表明多巴胺是一种候选的神经递质系统，参与刺激没有高度交流动机的个体的交流。本文提出的实验验证了一种假设，即情境性交流的个体差异取决于与动机和奖励相关的神经系统中的多巴胺活动。为了验证这一假设，我们将研究位点特异性多巴胺损伤（目的1）和位点特异性多巴胺受体亚型操纵（目的2）对低沟通和高沟通个体在目标导向和社会动机环境下的沟通的影响。受这些操作影响的神经回路将在行为测试后通过检查神经元活动标记物和其他神经化学标记物来检查。然后，在两种情况下，将对低传播者和高传播者的多种多巴胺能标记物进行比较，以确定大脑中与情境适当沟通的自然个体差异相关的差异（目标3）。拟议的研究将确定刺激情境适当的社会互动的操作，这可以用于设计缺乏交流动机的人类临床干预措施。建议的研究范围从神经元到神经回路，再到复杂的社会行为，将已知的动机与交流研究结合起来，研究环境和社会背景对表现出自然行为变化的个体的影响，并将为精神疾病个体提供治疗思路。社会沟通障碍是包括自闭症谱系障碍在内的几种精神障碍的标志。这类障碍的特点是，在交流的动机和从事适合社会的交流的能力方面，存在极端的个体差异。拟议的研究将确定刺激情境适当的社会互动的操作，这可以用于设计缺乏交流动机的人类临床干预措施。

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.