The role of serotonergic action in amygdala in rodent prosocial behavior

亲社会选择，即对其他个体产生利益的结果的偏好，在人类互动中无处不在。然而，尽管最近在人类和动物方面都取得了进展，但亲社会行为的行为和神经基础仍然不清楚。在DFG支持的第一个资助期内，我们开发了一项任务来评估大鼠的亲社会选择行为。我们发现，老鼠表现出对为其他老鼠带来好处的结果的偏好;因此，它们的行为符合亲社会的标准。动物之间的亲社会倾向有很大程度的异质性，一些大鼠表现出非常强的亲社会偏好，而其他大鼠对奖励的产生漠不关心。此外，我们获得的初步证据表明，啮齿类动物的外侧眶额皮质（IOFC）是重要的，从非社会背景下的社会，这表明，IOFC最终参与决定谁来帮助，谁不。然而，目前还不清楚哪些其他大脑结构支持亲社会行为与IOFC一致，并且潜在的精神药理学完全难以捉摸。基于对社会认知、目标导向行为和强化学习的研究证据，我们假设基底外侧杏仁核（BLA）是管理社会行为的中枢，并且该功能由BLA中的5-羟色胺（5-HT）作用支持。为了验证这一预测，我们将在亲社会选择任务的自动化版本中训练大鼠。在这项任务中，两只大鼠，一个演员和一个伙伴大鼠，在一个双T型迷宫中互动。行动大鼠总是第一个行动者，并在两个选择隔室之间进行选择，这两个隔室要么只给它们一个奖励，在它们的隔室中提供（自己的奖励; OR），要么自己的奖励加上放在相邻隔室中的伴侣大鼠的额外奖励（都是奖励; BR）。在第一个实验中，我们计划将病变应用于BLA，并将病变大鼠的亲社会倾向（% BR选择）与具有假病变的对照大鼠的倾向进行比较。在随后的两个实验中，我们将检查局部微量注射5-羟色胺5-HT 1A受体激动剂（8-OH-DPAT）和拮抗剂（WAY-100，635）到双侧BLA对亲社会行为的影响。我们的研究结果与一个社会相关问题高度相关：精神病。精神病的特征是杏仁核功能障碍以及多巴胺能稳态失调。因此，我们的研究将为进一步理解以精神病和反社会行为为特征的疾病提供重要的一步。

Prosocial choice, the preference for outcomes that produce benefits for other individuals, is ubiquitous in human interactions. However, despite recent advances in both humans and animals, the behavioral and neural bases of prosocial behavior remain unclear. In a first funding period supported by DFG, we have developed a task to assess prosocial choice behavior in rats. We found that rats revealed preference for outcomes that produced benefits for other rats; their behavior hence qualified as prosocial. There was a substantial degree of heterogeneity in the prosocial tendencies between animals, with some rats showing very strong prosocial preferences, while other rats being indifferent to the production of reward to their conspecifics. Moreover, we obtained preliminary evidence showing that the rodent lateral orbitofrontal cortex (lOFC) was important for disambiguating social from non-social contexts, suggesting that lOFC was ultimately involved in determining whom to help and whom not. However, it is unclear which other brain structures support prosocial behavior in concert with lOFC, and the underlying psychopharmacology is entirely elusive. We hypothesize, based on evidence from research on social cognition, goal-directed behavior and reinforcement learning, that basolateral amygdala (BLA) is a central hub for managing social behavior, and that this function is supported by serotonin (5-HT) action in BLA. To test this prediction, rats will be trained in an automated version of our prosocial choice task. In this task, two rats, an actor and a partner rat, interact in a double T-maze. Actor rats are always first movers and choose between two choice compartments yielding either just a reward for them, delivered in their compartment (own reward; OR), or own reward plus an additional reward for the partner rat placed in an adjacent compartment (both reward; BR). In a first experiment, we plan to apply lesions to BLA and compare the prosocial tendencies of the lesioned rats (% BR choices) to the tendencies of control rats with sham lesions. In two subsequent experiments, we will examine the effects of local microinjections of serotonin 5-HT1A receptor agonists (8-OH-DPAT) and antagonists (WAY-100,635) into bilateral BLA on prosocial behavior. Our results are of high relevance for a societally pertinent problem: psychopathy. Psychopathy is characterized by amygdala dysfunction as well as dysregulated serotonergic homeostasis. Our studies will therefore provide an important step in furthering our understanding of disorders characterized by psychopathy and antisocial behavior.