Fear and Reward: Role of Dopamine in Predictive Learning

对世界做出预测并用新信息更新这些预测的能力对日常运作至关重要。目前的研究计划试图阐明多巴胺和靶向大脑结构是如何处理预测性学习的建立的，以及面对胃口和厌恶环境中不断变化的偶然性，这些预测如何被修改。该项目将采用因果(光遗传学)和相关(体内电生理学)神经科学技术相结合的方法，以研究特定神经元类型(多巴胺细胞)的激发和抑制如何导致接受直接多巴胺输入的大脑区域的学习、行为和神经放电的变化。这个项目将专门寻求确定多巴胺是否以类似或相反的方式处理学习恐惧和奖励的过程。这将通过采用模块化设计并检查多巴胺是否通过纠错或价值机制来调节学习，它是否在调节注意力过程中发挥作用，以及确定在预测时多巴胺信号携带什么信息，以及抑制这一信号是否使学习和神经放电恢复到预期的奖励来完成。这项研究将通过观察恐惧和奖励学习，更广泛地揭示多巴胺在学习中的作用。这项工作还将试图研究在先前建立的联系被修改或更新的情况下，尤其是当预期结果大于预期结果时，多巴胺如何调节下游大脑区域的处理。这种训练定义了在刺激之间已经建立的预测关系中减少或消退的条件。通过审查电路的参与，本提案将导致对信息如何传播到目标结构以便处理预测的更全面的理解。此外，通过研究在奖励和恐惧环境中如何建立联系以及如何消除联系的神经生物学，拟议的研究对于改善我们对情感障碍(例如，恐惧症、焦虑、创伤后应激)、药物和食物成瘾的动物模型以及最终人类体验的理解具有重要的益处。因此，这里提出的研究试图与学者一起向临床医生和普通民众进行交流，并强调动物工作在治疗发展中的重要性。此外，Iordanova博士开展的研究的多样性将有助于培养新一代科学家的各种分析和技术技能。

The ability to make predictions about the world and update those predictions with new information is essential to everyday functioning. The current research program seeks to shed light on how dopamine and target brain structures processes the establishment of predictive learning and how these predictions can be modified in the face of changing contingencies in the appetitive and aversive settings. The project will employ a combination of causal (optogenetics) and correlational (in vivo electrophysiology) neuroscience techniques in order to examine how excitation and inhibition of specific neuronal types (dopamine cells) lead to alternation in learning, behavior, and neural firing in brain areas that receive direct dopamine input. This project will specifically seek to determine whether dopamine processes learning about fear and reward in similar or opposing fashion. This will be done by employing a blocking design and examining whether dopamine regulates learning via error-correcting or value mechanisms, whether it plays a role in regulating attentional processes, as well as determine what information is carried by the dopamine signal at time of prediction and whether inhibiting this signal reinstates learning and neural firing to expected rewards. This research will shed important light on dopamine function in learning more generally by looking at both fear and reward learning.This work will also seek to examine how dopamine modulates processing in downstream brain areas under conditions when previously established associations are modified or updated in particular when expected outcomes are greater than those delivered. Such training defines the conditions for reduction or extinction in the already established predictive relationship between stimuli. By examining the involvement of circuits, the present proposal will lead to more holistic understanding of how information is propagated to target structures in order to process predictions. Furthermore, by examining the neurobiology of how associations are established and in turn extinguished in both the reward and fear settings, the proposed research carries important benefit to improving our understanding of animal models of disorders of affect (e.g., phobias, anxiety, post-traumatic stress) drug and food addiction, and ultimately the human experience. Thus the research proposed here seeks to speak to clinicians and the general population alongside academics and underscores the importance of animal work in treatment development. In addition, the diversity of the research carried by Dr Iordanova will served to develop a variety of analytical and technical skills in the new generation of scientists.