The Role of Transient Striatal Dopamine Release Events in Negative Reinforcement Processes

评估和避免负面结果对于最佳决策以及最终的动物生存至关重要。众所周知，当动物追求奖励时，大脑中有一种叫做多巴胺的化学物质会促进有利的行为；然而，人们对多巴胺在动物躲避伤害时的作用知之甚少。首席研究员的实验室能够使用一种叫做伏安法的工具来实时测量行为动物大脑中的多巴胺水平，并使用一种叫做光遗传学的工具来打开或关闭多巴胺神经元。利用这些工具，研究者的研究小组将对行为老鼠大脑中的多巴胺水平如何参与避免足震进行全面评估。其他实验旨在确定多巴胺是否参与评估避免不同强度足震的价值。据预测，多巴胺水平将在学习过程中以一种促进成功避免足震的方式发生变化，并与避免足震的价值成比例。拟议项目的所有方面都将涉及本科生受训人员，特别是来自代表性不足人口的受训人员。通过使用尖端技术来研究多巴胺在避免伤害中的作用，首席研究员和他的学生将发现有关行为背后的神经生物学机制的新信息，同时发展未来，多样化的科学家群体。首席研究员最近证明，预测避免厌恶事件的警告信号会引起腹侧纹状体内多巴胺浓度的短暂激增。这一发现表明，短暂的多巴胺信号代表了环境刺激，预测了对坏事的避免，就像预测了对好事的接受一样。此外，初步的光遗传学数据显示，在训练有素的大鼠中，在警告信号呈现期间促进中脑多巴胺神经活动可促进回避结果。尽管有这些重要的进展，短暂多巴胺释放事件在负强化过程中的确切作用仍然未知。在本项目中，研究者及其研究小组将利用快速扫描循环伏安法和光遗传学技术来评估伏隔核核心、背内侧纹状体和背外侧纹状体在1)回避学习、2)回避的维持和消除以及3)正强化值与负强化值评估过程中瞬时多巴胺释放事件的作用。这些数据的收集将产生目前未知的关于大脑如何处理负强化的机制细节——这些信息可能有助于更细致地理解多巴胺在动物行为中的作用。为了实现这些目标，研究者将让本科生参与数据收集和传播的各个方面，特别是那些来自代表性不足背景的学生。此外，研究者将为来自弱势群体的本科生开发一个国际神经科学会议体验项目，并为来自弱势群体的本科生开发一个神经科学拓展项目，在该项目中，来自弱势群体的本科生参观丹佛市的博物馆和学校，向公众传授有关大脑的知识。

Evaluating and avoiding negative outcomes is critical for optimal decision-making and, ultimately, animal survival. A chemical in the brain called dopamine is well known to promote advantageous behavior when animals are pursuing reward; however, little is known regarding the role of dopamine when animals are avoiding harm. The principal investigator's lab is able to measure real-time dopamine levels in the brain of behaving animals using a tool called voltammetry, and turn dopamine neurons on/off using a tool called optogenetics. Using these tools, the investigator's research team will perform a thorough assessment of how dopamine levels within the brains of behaving rats are involved in the avoidance of footshock. Additional experiments serve to determine whether dopamine is involved in assessing the value of avoiding different intensities of footshock. It is predicted that dopamine levels will change over the course of learning in a manner that promotes successful footshock avoidance and scale with the value of the footshock avoided. All aspects of the proposed project will involve undergraduate trainees, especially trainees from underrepresented populations. By using cutting-edge technologies to investigate the role of dopamine in the avoidance of harm, the principal investigator and his students will uncover novel information about the neurobiological mechanisms underlying behavior while simultaneously developing a future, diverse population of scientists.The principal investigator recently demonstrated that a warning signal predicting the avoidance of an aversive event evokes transient surges in dopamine concentration within the ventral striatum. This finding suggests that the transient dopamine signal represents environmental stimuli predicting the avoidance of something bad similarly to those predicting the receipt of something good. Furthermore, preliminary optogenetics data reveal that facilitating midbrain dopamine neural activity during warning signal presentation promotes avoidance outcomes in well-trained rats. Despite these important advances, the precise role(s) that transient dopamine release events play in negative reinforcement processes remains unknown. In this project, the investigator and his research team will use fast-scan cyclic voltammetry and optogenetics to assess the role of transient dopamine release events in the nucleus accumbens core, dorsomedial striatum, and dorsolateral striatum during: 1) avoidance learning, 2) maintenance and extinction of avoidance, and 3) positive vs. negative reinforcement value assessment. The collection of these data will generate presently unknown mechanistic detail regarding how the brain processes negative reinforcement-- information that may contribute to a more nuanced understanding of the role of dopamine in animal behavior. To accomplish these goals, the investigator will involve undergraduate students, particularly those from underrepresented backgrounds, in all aspects of data collection and dissemination. In addition, the investigator will develop an international neuroscience conference experience program for undergraduate students from underrepresented minorities and a neuroscience outreach program in which undergraduate students from underrepresented minorities visit Denver city museums and schools to teach the general public about the brain.