Neural mechanisms of affective processing in prefrontal-limbic circuits

项目总结 快感缺乏是情绪障碍和焦虑症的典型症状，其特征是 来自有益经历的积极影响。当前的快感缺乏症理论强调它由两个部分组成 不同的组成部分：一个与对回报的期望有关，另一个与从获得中获得的快乐有关 奖励。在单个神经元水平上理解大脑如何处理预期和接受奖励 因此，这是基础神经科学面临的关键挑战。影像研究表明前额叶的一部分 大脑皮质，当期望得到奖励时，扣带回皮质(ACC)是活跃的，并在 快感缺乏症患者。证实这一发现的是，来自对患有脑部疾病的猴子的研究数据 扣带下前交叉韧带表明，这一区域对于与期望有关的行为很重要，但对收据并不重要 奖赏。然而，到目前为止，还没有一种方法能够提供电路级别的理解，即 扣带下前交叉韧带影响奖赏期望。这一层次的理解对于大脑的深层来说是重要的 对部分患者的快感缺乏进行刺激，可缓解部分患者的快感缺失。这 假设干预是通过改变扣带下ACC和任一 扁桃体或腹侧纹状体。在控制与奖励相关的行为方面，哪种途径更重要 期望或必要的活动模式是未知的。我们的目标是确定神经机制 在期望得到奖赏的时候，参与胼胝体下的ACC-杏仁核-VS环路。我们 假设扣带下前扣带回的作用是调节腹侧纹状体内的奖赏编码 杏仁核在奖励期待中，而不是在收到时。为了检验我们的假设，我们将使用一种创新的 单神经元记录、场电位记录、电刺激、扩散成像的组合 方法和化学遗传学分析奖赏相关神经反应的时间和LFP一致性 在正常生理条件下的三个部位中，当扣带下前交叉韧带中的神经元慢性地 使用化学发生方法激活，以及在正常情况下应用急性电刺激时 条件和该地区被长期激活的时间。实现这些目标将从根本上推动我们的 了解控制奖赏相关行为和神经的神经回路和活动模式 灵长类动物的活动，并提供电路水平的理解如何影响扣带下ACC 预期的奖励处理。这种水平的理解有可能提供信息并帮助完善途径- 对所有以从奖励中失去愉悦为特征的疾病的特殊干预，如抑郁症 还有精神分裂症。

Project summary Anhedonia is a defining symptom of mood disorders and anxiety disorders and is characterized by a loss of positive affect from rewarding experiences. Current theories of anhedonia emphasize that it consists of two distinct components: one is related to the expectation of reward, the other to the pleasure from receiving rewards. Understanding how the brain processes expected and received rewards at the level of single neurons is therefore a key challenge for basic neuroscience. Imaging studies indicate that one part of the prefrontal cortex, the subcallosal anterior cingulate cortex (ACC) is active when rewards are expected and is altered in individuals with anhedonia. Corroborating this finding, data from studies of monkeys with lesions of the subcallosal ACC indicate that this area is important for behavior related to the expectation, but not the receipt of rewards. However, no approach to date has been able to provide a circuit-level understanding of how the subcallosal ACC influences reward expectation. This level of understanding is important as deep brain stimulation of subcallosal ACC and nearby white matter pathways alleviates anhedonia in some patients. This intervention is hypothesized to work by altering functional interaction between subcallosal ACC and either amygdala or ventral striatum. Which pathway is more important for controlling behavior related to reward expectation or the requisite activity patterns is unknown. Our goal here is to determine the neural mechanisms engaged in the subcallosal ACC-amygdala-VS circuit when rewards are expected and then received. We hypothesize that the role of the subcallosal ACC is to modulate reward encoding within ventral striatum and amygdala during reward expectation, but not receipt. To test our hypothesis we will use an innovative combination of single-neuron recordings, field potential recordings, electrical stimulation, diffusion imaging methods, and chemogenetics analyzing the timing of reward-related neural responses and LFP coherence among the three sites under normal physiological conditions, when neurons in subcallosal ACC are chronically activated using chemogenetic methods, and when acute electrical stimulation is applied both under normal conditions and when the area is chronically activated. Completing these aims will fundamentally advance our understanding of the neural circuits and activity patterns that control reward-related behavioral and neural activity in primates as well as providing a circuit level understanding of how subcallosal ACC influences expected reward processing. This level of understanding has the potential to inform and help refine pathway- specific interventions for all disorders characterized by a loss pleasure from reward, such as depression as well as schizophrenia.