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。社交障碍是几种精神障碍的标志，包括自闭症谱系障碍。这类障碍的特点是在沟通动机和参与社会适当沟通的能力方面存在极端的个体差异，但很少有研究致力于了解这些问题的神经基础。鸣禽为研究调节适当社会交流的大脑机制提供了一个理想的模型系统。在我们的模型物种中，我们发现大脑在歌曲针对女性(目标导向)和在大型社会群体中观察到的歌曲(群体动机)的背景下，对交流进行不同的调节。在过去的研究中，我们发现一些人在高层沟通，而另一些人则根本不沟通。与交流的个体差异相关的是大脑中涉及动机和奖励的区域活动的差异。我们已经能够通过对多巴胺受体的药物操纵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，参与刺激没有高度动机进行交流的个体的交流。这里提出的实验验证了这样一种假设，即在与背景相适应的交流中，个体差异取决于参与动机和奖励的神经系统中的多巴胺活动。为了验证这一假设，我们将检验特定部位多巴胺损伤(目标1)和特定部位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交动机背景下沟通的影响。在通过神经活动标志物和其他神经化学标志物的检查进行行为测试后，将检查受这些操作影响的神经回路。然后，将对两种情况下低和高通信者的多个多巴胺能标志物进行比较，以确定大脑中与环境相适应的交流中自然的个体差异相关的差异(目标3)。这项拟议的研究将确定刺激与背景相适应的社会互动的操作，这些操作可用于设计对缺乏沟通动机的人类进行临床干预。拟议中的研究跨越了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相结合，考察环境和社会背景对表现出行为自然变化的个人的影响，并将为患有精神疾病的个人提供治疗思路。社交障碍是几种精神障碍的标志，包括自闭症谱系障碍。这类障碍的特点是在沟通动机和参与社会适当沟通的能力方面存在极端的个体差异。这项拟议的研究将确定刺激与背景相适应的社会互动的操作，这些操作可用于设计对缺乏沟通动机的人类进行临床干预。

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.