Neural Mechanisms of Decisions Made in the Context of Social Distress

项目摘要 认识到他人的情绪指导我们的日常决策。我们的行为有益于他人， 压制那些可能造成伤害或痛苦的人，即使这需要个人的牺牲。识别 一个同种的痛苦和能力，以改变自己的行为，根据这种痛苦是中断在几个 精神障碍（例如，自闭症、精神病）。不幸的是，我们对 控制这些功能的神经生物学基质，因为在动物中， 和神经递质水平尚未发生。最近，有一些行为研究 证明啮齿类动物可以识别同种的痛苦，并选择改变行为来减轻这种痛苦。 痛苦在这里，我们建议使用尖端的神经科学技术-设计师受体独家 由设计师药物（DREADDS）激活，同时在多个大脑区域进行单单位记录， 快速扫描循环伏安法（FSCV），光遗传学和钙成像-以阐明神经 在多种社会环境中，与同种痛苦期间奖励导向行为的修改相关的机制 背景和时间尺度作为意外事件是学习和社会关系的变化与经验。我们 我提出了一个回路，通过这个回路，行为被预测的社会痛苦所调制，通过相互作用， 基底外侧杏仁核（ABL）、前扣带皮层（ACC）、丘脑核心核（NAc）和 多巴胺（DA）释放。该电路内区域之间的动态关系将是 在学习和长期的社会互动过程中， 同时记录多个大脑区域的信息，并确定是否改变了交流（DREADDS） 影响行为。钙成像将使我们能够监测单个神经元的活动 和大量的神经元。我们将联合分析不同时间的图像 确定不同时间点的共同点和变化点，并从统计学上确定 组件如何与行为相关，以确定区域如何在内部处理社会信息 网络级。我们预测ABL-ACC回路在同种痛苦的配对识别中是重要的 与预测刺激，是必要的相关动机行为在NAc被修改， 社会背景此外，行政协调会将更多地参与共同登记与下列方面有关的信息： 在学习过程中依赖于ABL。我们还推测DA释放 通过报告阴性和阳性来调节下游靶标（如NAc）中的预测值信号 当奖励伴随着同种的痛苦和休克回避时，预测错误。最后我们 提出实验，试图通过光遗传学刺激来调节亲社会和反社会行为 和多巴胺系统的抑制，并通过催产素给药，一种新的治疗精神疾病的治疗方法， 以社会功能障碍为特征的疾病。

PROJECT SUMMARY Recognizing the emotions of others guides our daily decisions. We perform actions that benefit others and suppress those that might cause harm or distress, even when it requires personal sacrifice. The recognition of a conspecific's distress and ability to alter ones behavior in light of that distress is disrupted in several psychiatric disorders (e.g., autism, psychopathy). Unfortunately, we know very little about the neurobiological substrates that control these functions because detailed work in animals at the single-unit and neurotransmitter level has not yet occurred. Recently, there have been a number of behavioral studies demonstrating that rodents can recognize conspecific distress and choose to alter behavior to alleviate that distress. Here, we propose to use cutting edge neuroscience techniques – Designer Receptors Exclusively Activated by Designer Drugs (DREADDS), single-unit recording across multiple brain areas simultaneously, fast-scan cyclic voltammetry (FSCV), optogenetics, and calcium imaging – to elucidate the neural mechanisms related to modification of reward-guided behavior during conspecific distress in multiple social contexts and time scales as contingencies are learned and social relationships change with experience. We propose a circuit by which behaviors are modulated by predicted social distress via interactions between basolateral amygdala (ABL), anterior cingulate cortex (ACC), nucleus accumbens core (NAc), and accumbal dopamine (DA) release. The dynamic relationship between areas within this circuit will be uncovered with precise spatial and temporal resolution during learning and long-term social interaction by recording from multiple brain areas simultaneously and determining if altered communication (DREADDS) between areas impacts behavior. Calcium imaging will allow us to monitor activity across single neurons and large groups of neurons over multiple days. We will jointly analyze images at different time instances and determine what is common across time points versus what has changed, and statistically determine how components correlate with behavior to determine how areas process social information at an internal network level. We predict that the ABL-ACC circuit is important for pairing recognition of conspecific distress with predictive stimuli and is necessary for correlates related to motivated behavior in NAc to be modified in social contexts. Furthermore, ACC will be more heavily involved in co-registering information pertaining to oneself and the conspecific, but is dependent on ABL during learning. We also theorize that DA release modulates predictive value signals in downstream targets such as NAc by reporting negative and positive prediction errors when rewards are accompanied by conspecific distress and shock avoidance. Finally, we propose experiments that will attempt to modulate pro- and anti-social behavior via optogenetic stimulation and inhibition of the DA system and by oxytocin administration, a novel therapeutic treatment for mental disorders characterized by social dysfunction.