Resolving the role of VTA dopamine and GABA neurons in associative learning

解析 VTA 多巴胺和 GABA 神经元在联想学习中的作用

• 批准号: 10749667
• 负责人: Margaret E Stelzner
• 金额: $ 3.5万
• 依托单位: UNIVERSITY OF MINNESOTA
• 依托单位国家: 美国
• 财政年份: 2023
• 资助国家: 美国
• 起止时间: 2023-09-01 至 2026-05-31
• 项目状态: 未结题
• 来源: https://reporter.nih.gov/project-details/10749667
• 关键词: Animals; Association Learning; Behavior; Behavioral; Brain region; Calcium; Color; Computing Methodologies; Conflict (Psychology); Consumption; Cues; Decision Making; Desire for food; Disease; Disinhibition; Dopamine; Elements; Environment; FLP recombinase; Fiber; Floor; Genetic; Goals; Halorhodopsins; Imaging Device; In Situ Hybridization; Learning; Motivation; Neurons; Outcome; Photometry; Play; Population; Prevalence; Process; Rattus; Rewards; Role; Shock; Signal Transduction; Stimulus; Sucrose; Synapses; Synaptic plasticity; Testing; Time; Training; Ventral Tegmental Area; Viral; calcium indicator; cost; dopaminergic neuron; experience; experimental study; food consumption; gamma-Aminobutyric Acid; in vivo; insight; motivated behavior; neurobiological mechanism; neurotransmission; novel; optogenetics; promoter; recruit; response; selective expression; sensor; tool; transmission process

PROJECT SUMMARY Associating stimuli in the environment to biologically relevant outcomes, such as reward or threat, is necessary to survive and foundational to decision making. Given the prevalence of disordered decision making, there is a pressing need to understand the basic neurobiological mechanisms of associative learning underlying cue-guided motivation and behavior. The Ventral Tegmental Area (VTA) is essential to this behavioral process through its two main neuronal subtypes: dopamine (DA) and GABA. GABA neurons synapse directly onto local DA neurons and modulate DA transmission. DA neurons increase activity to cue-reward associations, modulating firing based on the extent to which reward predicted matches reward expected in a phenomenon known as reward prediction error (RPE). GABA neurons also increase activity in reward learning and their signaling contributes to RPE DA dynamics. In contrast, DA neurons are inhibited in aversive contexts while GABA neurons increase activity. Given VTA GABA’s role in both appetitive and aversive processing, these neurons may be uniquely engaged to integrate valence in decision making. Understanding the role of these neurons in multi-valent learning is important, because behavior often takes place in situations of motivational conflict, where opposing goals (i.e., consuming food and avoiding threats) occur simultaneously, requiring the appetitive and aversive elements to be weighed and integrated to guide choices. This proposal will make use of new tools to target, record, and manipulate VTA DA and GABA neurons, to investigate their functional connectivity (Aim 1) and their roles in valence integration (Aim 2). First, I will optogenetically inhibit GABA neurons while recording the activity of VTA DA neurons through in vivo fiber photometry. These experiments will test the hypothesis that the VTA GABA modulates local DA neurons and this relationship can change with experience. I will also manipulate and record DA and GABA dynamics during a motivational conflict task in which there are two opposing goals (consuming sucrose and avoiding shock) to dissect the roles these populations play in valence integration. These studies will test the hypothesis that VTA DA and GABA neurons produce value and salience signals, respectively, that are collectively necessary to integrate valence, for dynamic reward seeking.

项目总结 将环境中的刺激与生物相关的结果联系起来，如奖励或威胁，是必要的。 为了生存，也是决策的基础。鉴于无序决策的盛行，有一种 迫切需要了解联想学习的基本神经生物学机制 线索引导的动机和行为。腹侧被盖区(VTA)对这一行为过程是必不可少的 通过它的两个主要神经元亚型：多巴胺(DA)和GABA。GABA神经元直接突触到局部 DA神经元和调制DA传递。DA神经元增加了线索-奖赏联系的活动， 基于在现象中预测的奖励与预期的奖励匹配的程度来调制激发 称为奖励预测误差(RPE)。GABA神经元也增加了奖赏学习的活动和它们的 信令有助于RPE DA动态。相反，DA神经元在厌恶的环境中受到抑制，而 GABA神经元增加活动。鉴于VTA GABA在欲望和厌恶加工中的作用，这些 神经元可能是唯一参与在决策中整合价态的人。了解这些因素的作用 神经元在多价学习中很重要，因为行为通常发生在动机情境中。 冲突，即相反的目标(即，消费食物和避免威胁)同时发生，需要 食欲和厌恶的因素被权衡和整合，以指导选择。这项提议将使 使用新工具来靶向、记录和操纵VTA DA和GABA神经元，以研究 它们的功能连接性(目标1)和它们在价整合中的作用(目标2)。首先，我会 光遗传抑制GABA神经元同时记录VTA DA神经元的活体纤维活动 测光学。这些实验将检验VTA GABA调节局部DA神经元和 这种关系可以随着经验的变化而改变。我还将操作和记录DA和GABA的动态 动机冲突任务，其中有两个相反的目标(消耗蔗糖和避免休克) 剖析这些群体在价整合中所扮演的角色。这些研究将检验VTA的假设 DA和GABA神经元分别产生价值和显著信号，这是共同必需的 积分价，用于动态奖赏寻求。