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，健康的社会交往的核心。社交障碍是包括自闭症谱系障碍在内的几种精神障碍的标志。这种疾病的特点是在沟通的动机和参与社会适当的沟通能力方面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，在其中研究大脑机制调节适当的社会交流。在我们的模型物种中，我们发现大脑在歌曲指向女性（目标导向）与在大型社会群体中观察到的歌曲（群体动机）的背景下差异调节通信。在过去的研究中，我们发现有些人在高水平上交流，而另一些人则根本没有。与交流中的个体差异相关的是大脑中涉及动机和奖励的区域的活动差异。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那些没有高度交流动机的个体的交流。这里提出的实验测试的假设，即在上下文适当的通信的个体差异取决于多巴胺的神经系统内的活动参与动机和奖励。为了验证这一假设，我们将研究特定位点多巴胺病变（目标1）和特定位点多巴胺受体亚型操纵（目标2）对低沟通和高沟通个体目标导向和社会动机背景下沟通的影响。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的标志物和其他神经化学标志物进行检查。然后，在这两种情况下，将在低和高沟通者中进行多个多巴胺能标记物的比较，以确定与背景适当的沟通中的自然个体差异相关的大脑差异（目的3）。拟议的研究将确定刺激上下文适当的社会互动的操作，这可用于设计临床干预措施，在人类的动机沟通赤字。拟议的研究范围从神经元到神经回路，再到复杂的社会行为，将已知的动机与沟通研究相结合，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，并将为患有精神疾病的个体提供治疗思路。社交沟通缺陷是包括自闭症谱系障碍在内的多种精神障碍的标志。这种障碍的特点是在沟通的动机和参与社会适当沟通的能力方面存在极大的个体差异。拟议的研究将确定刺激上下文适当的社会互动的操作，这可用于设计临床干预措施，在人类的动机沟通赤字。

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.