A New Animal Model of Social Reward

 描述(由申请者提供)：早期社会奖励的中断可能会对技能的发展产生毁灭性的影响，例如开始联合注意和发声交流。由于现有的大多数社会奖励动物模型都集中在成人身上，因此需要一个新的模型来理解青少年社会发展的早期关键期。这项拟议工作的目标是通过建立青少年与照顾者互动的早期社会奖励的动物模型来填补这一空白。为了实现这一目标，研究小组将开发一种测试方法，以量化和关联年轻斑马雀的社会动机、社会偏好和声音发展。这种方法的基本原理如下：首先，即使在斑马雀开始唱歌之前，它们就非常有动力听到成人的歌声，并会按键进入歌声。因此，社会动机可以很容易地量化。其次，青少年的歌曲学习取决于社交活动(例如，按键听歌)，也可以使用既定的方法进行量化，使团队能够测试社交动机和发声学习之间的关系。第三，幼雀更喜欢从照顾者那里学习歌曲，而不是不熟悉的成年人，这让他们有机会了解早期的社会经验如何决定社会偏好，以及这些偏好如何推动发声学习。在目标1中，研究小组将开发一种分析方法，以获得在感觉运动声音发育的整个轨迹上这些过程的密集采样的纵向数据。这一目标的一个关键创新将是使用新的计算方法，最初是为了了解社会定向对人类儿童发声发展的贡献，在这个新的动物模型中显示社会动机、社会偏好和发声发展之间的关系。Aim 1将开发一种工具来评估药物操纵和社会奖励途径中的基因敲除的行为影响，从而能够精确地描述相关的神经回路。为了开始利用新的测试方法，在目标2中，研究小组将测试催产素受体(OTR)阻断对社会偏好和发声学习发展的影响。这些目标背后的中心假设是，在发育早期发出OTR信号，取决于与照顾者的社会互动，引导青少年优先照顾该照顾者。因此，青少年会更准确地模仿照顾者的发声。第二个关键创新是，该项目将扩大我们对催产素的理解，将社会发展和学习的关键时期包括在内--这两者都是潜在的丰富但严重欠发达的研究领域。这项新的测试将有可能在亲子互动的背景下对青少年发起的社交出价进行建模，以及社会奖励和语音交流发展之间的关系。由于该物种世代时间短，可以维持相对较大的数量，该检测将为理解早期社会奖励背后的神经机制及其破坏的发育后遗症提供新的重要机会。

 DESCRIPTION (provided by applicant): Early disruption of social reward can have devastating effects on the development of skills such as initiation of joint attention and vocal communication. Because most existing animal models of social reward focus on adults, a new model is needed for understanding early critical periods of social development in juveniles. The objective of the proposed work is to fill that gap by establishing an animal model of early social reward in juveniles interacting with caregivers. To achieve this goal, the research team will develop an assay to quantify and interrelate social motivation, social preferences, and vocal development in young zebra finches. The rationale for this approach is as follows: First, even before they begin to sing, young zebra finches are highly motivated to hear adult song and will key-press for access to it. Thus, social motivation can be easily quantified. Second, song learning in juveniles is contingent upon social bids (e.g., key presses to hear song) and can also be quantified using established methods, allowing the team to test for relationships between social motivation and vocal learning. Third, young finches prefer to learn song from caregivers rather than unfamiliar adults, providing the opportunity to understand how early social experience dictates social preferences and how those preferences drive vocal learning. In Aim 1, the team will develop an assay to obtain densely sampled, longitudinal data on these processes over the entire trajectory of sensorimotor vocal development. A key innovation of this aim will be to use novel computational methods, originally developed to understand the contributions of social orienting to vocal development in human children, to show the relationships among social motivation, social preferences, and vocal development in this new animal model. Aim 1 will produce a tool to assess the behavioral effects of pharmacological manipulations and gene knockdown within social reward pathways, allowing precise characterization of the relevant neural circuits. To begin capitalizing on the new assay, in Aim 2 the team will test the effects of oxytocin receptor (OTR) blockade on the development of social preferences and vocal learning. The central hypothesis underlying these aims is that OTR signaling early during development, contingent with social interactions with a caregiver, directs juveniles to attend preferentially to that caregiver. As a result, juveniles will more accurately copy that caregiver's vocalizations. A second key innovation is that the project will expand our understanding of oxytocin to include critical periods of social development as well as learning-both of which are potentially rich but grossly underdeveloped areas of research. The new assay will make it possible to model juvenile-initiated social bids in the context of parent-offspring interactions, as well as the relationship between social reward and the development of vocal communication. Because this species has a short generation time and can be maintained in relatively large numbers, the assay will provide new, important opportunities for understanding the neural mechanisms underlying early social reward and the developmental sequelae of its disruption.