Corticothalamic circuits mediating behavioral adaptations to unexpected reward omission

皮质丘脑回路介导对意外奖励遗漏的行为适应

• 批准号: 10734683
• 负责人: Michael Beierlein
• 金额: $ 60.11万
• 依托单位: UNIVERSITY OF TEXAS HLTH SCI CTR HOUSTON
• 依托单位国家: 美国
• 财政年份: 2023
• 资助国家: 美国
• 起止时间: 2023-07-13 至 2028-04-30
• 项目状态: 未结题
• 来源: https://reporter.nih.gov/project-details/10734683
• 关键词: Amygdaloid structure; Animal Behavior; Animals; Anterior; Anxiety Disorders; Area; Attenuated; Behavior; Behavioral; Behavioral Paradigm; Brain; Cell Nucleus; Conditioned Stimulus; Conflict (Psychology); Cues; Desire for food; Detection; Dopamine; Electrophysiology (science); Exposure to; Extinction; Food; Frequencies; Frustration; Glutamates; Human; In Vitro; Laboratory Rat; Lead; Maintenance; Mediating; Mental Depression; Modification; Motivation; Movement; Neurons; Nucleus Accumbens; Organism; Outcome; Partner in relationship; Pathway interactions; Pattern; Phase; Population; Predictive Value; Prefrontal Cortex; Property; Rattus; Rewards; Role; Sensory; Shelter facility; Signal Transduction; Slice; Social Interaction; Structure; Structure of paraventricular nucleus of thalamus; Sucrose; Synapses; Synaptic plasticity; Testing; Thalamic structure; Training; Update; Ventral Tegmental Area; Water; attenuation; behavioral response; dopaminergic neuron; emotion regulation; emotional distress; experimental study; gain of function; genetic manipulation; in vivo; insight; loss of function; negative affect; neural; neural circuit; neuronal circuitry; optogenetics; photoactivation; pressure; response

PROJECT SUMMARY/ABSTRACT Environmental cues that are associated with food develop attractive and motivational properties that elicit reward-seeking behaviors in animals. However, when food-associated cues no longer lead to rewards, animals quickly adjust their behaviors by showing a transient increase of reward-seeking responses (invigoration) and a set of behavioral responses that resemble frustrative behaviors in humans. Repeated exposure to reward omission leads to behavioral attenuation that serves to suppress unproductive appetitive responses. Although significant progress has been made in elucidating the brain structures that regulate the acquisition and the extinction of reward-seeking responses, the neural circuits and brain mechanisms that control changes in behavioral responses during the initial phase of reward omission remain elusive. Emerging evidence suggests that neurons in the anterior portion of the paraventricular nucleus of the thalamus (aPVT) are activated by reward- associated cues and contribute to the regulation of emotional responses during unexpected omission of reward. Whereas activity in the aPVT to nucleus accumbens pathway decreases reward seeking, activity in the aPVT to central amygdala pathway increases it, suggesting that the aPVT is a potential candidate to regulate behavioral invigoration during reward omission. Here we propose to study how cortical and subcortical inputs to the aPVT regulate the dynamic activity of projection-defined aPVT neurons during reward omission. Using in vitro electrophysiology, we will study the intrinsic properties and synaptic dynamics of distinct aPVT neurons and their afferents. Using a food-seeking task in which rats are exposed to reward omission, we will investigate the neuronal activity patterns of aPVT neurons in vivo, and correlate their activity with the animal's behavior during the test. Subsequent gain-of-function and loss-of-function experiments will test the sufficiency and necessity of distinct aPVT afferents. These experiments will provide insights into the neural circuits that detect changes in reward availability and rapidly adjust animals' behavior during the initial phase of reward omission.

项目总结/摘要 与食物相关的环境线索会产生吸引力和激励性的特性， 动物的奖赏寻求行为然而，当与食物相关的线索不再导致奖励时， 快速调整他们的行为，表现出短暂的增加奖励寻求反应（振兴）和 类似于人类沮丧行为的一系列行为反应。重复暴露于奖励 忽略导致行为衰减，从而抑制非生产性的食欲反应。虽然 在阐明调节获得和获得的大脑结构方面已经取得了重大进展。 寻求奖励的反应消失，控制大脑变化的神经回路和大脑机制， 在奖励省略的初始阶段的行为反应仍然难以捉摸。新出现的证据表明 丘脑室旁核（aPVT）前部的神经元被奖赏激活， 相关的线索，并有助于调节情绪反应期间意外遗漏的奖励。 尽管aPVT到丘脑核途径的活动减少了奖赏寻求，但aPVT到丘脑核途径的活动减少了奖赏寻求。 中央杏仁核通路增加它，这表明aPVT是一个潜在的候选人，以调节行为 奖励缺失期间的激励。在这里，我们建议研究皮层和皮层下输入到aPVT 调节奖励遗漏期间投射定义的aPVT神经元的动态活动。使用体外 电生理学，我们将研究不同的aPVT神经元的内在特性和突触动力学及其 传入神经利用大鼠暴露于奖励遗漏的食物寻找任务，我们将研究 aPVT神经元在体内的神经元活动模式，并将它们的活动与动物的行为相关联， 考试随后的功能获得和功能丧失实验将测试 不同的aPVT传入。这些实验将提供对神经回路的深入了解， 奖励可获得性，并在奖励省略的初始阶段迅速调整动物的行为。