Neural mechanisms of affective processing in prefrontal-limbic circuits

项目摘要 快感缺失是心境障碍和焦虑症的定义性症状，其特征在于缺乏对情绪的控制。 积极的影响从有益的经验。目前的快感缺乏理论强调它包括两个方面 不同的组成部分：一个是与期望的回报，其他的快乐从接收 奖励了解大脑如何在单个神经元水平上处理预期和收到的奖励 因此是基础神经科学的一个关键挑战。影像学研究表明前额叶的一部分 当预期奖励时，胼胝体下前扣带皮层（ACC）是活跃的，并在 患有快感缺乏症的人支持这一发现的是，来自对患有脊髓损伤的猴子的研究数据。 胼胝体下前扣带回表明，该区域对与期望相关的行为很重要，但对接受不重要 奖励。然而，迄今为止还没有一种方法能够提供电路级的理解， 胼胝体下前扣带回影响奖赏期望。这种理解水平是重要的， 刺激胼胝体下ACC和附近的白色物质通路可加重某些患者的快感缺乏。这 假设干预是通过改变胼胝体下ACC与 杏仁核或腹侧纹状体。哪种途径对控制与奖励相关的行为更重要 期望或必要的活动模式是未知的。我们的目标是确定 当预期奖励并随后获得奖励时，参与胼胝体下ACC-杏仁核-VS回路。我们 假设胼胝体下ACC的作用是调节腹侧纹状体内的奖赏编码， 杏仁核在奖励的期望，但不是接收。为了验证我们的假设，我们将使用一个创新的 单神经元记录、场电位记录、电刺激、弥散成像的组合 方法和化学遗传学分析奖励相关的神经反应和LFP一致性的时间 在正常生理条件下，当胼胝体下ACC中的神经元慢性 使用化学发生方法激活，并且当在正常条件下施加急性电刺激时， 条件和当该地区是长期激活。实现这些目标将从根本上推动我们的 了解控制奖励相关行为和神经的神经回路和活动模式 活动在灵长类动物，以及提供一个电路水平的理解，如何胼胝体下ACC影响 预期奖励处理。这种理解水平有可能告知并帮助完善路径- 针对所有以奖励失去快乐为特征的疾病的具体干预措施，如抑郁症， 以及精神分裂症

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.