Corticothalamic circuits mediating behavioral adaptations to unexpected reward omission

项目摘要/摘要 与食物相关的环境线索会产生吸引人的和激励人的特性，从而引发 动物的奖赏行为。然而，当与食物相关的线索不再导致奖励时，动物 通过表现出一过性的奖励反应增加(激励)和 一组类似于人类挫折性行为的行为反应。反复暴露在奖励之下 省略会导致行为衰减，从而抑制非生产性的食欲反应。虽然 在阐明调节习得和脑功能的大脑结构方面取得了重大进展 奖赏反应的消亡，控制变化的神经回路和大脑机制 在奖励缺失的初始阶段，行为反应仍然难以捉摸。新出现的证据表明 丘脑室旁核(APVT)前部神经元被奖赏激活- 相关线索有助于调节意外遗漏奖赏时的情绪反应。 而aPVT至伏隔核通路的活动减少了奖赏寻求，而aPVT至伏核的活动 中央杏仁核通路使其增加，提示aPVT是调节行为的潜在候选者。 奖励遗漏中的激励。在这里，我们打算研究皮层和皮质下对aPVT的输入是如何 在奖赏缺失过程中调节投射限定的aPVT神经元的动态活动。在体外使用 电生理学，我们将研究不同的aPVT神经元和它们的内在属性和突触动力学 传入器。使用一项老鼠暴露于奖赏遗漏的觅食任务，我们将调查 活体aPVT神经元的神经元活动模式，以及它们的活动与动物在 这个测试。随后的功能增益和功能损失实验将测试以下各项的充分性和必要性 不同的aPVT传入。这些实验将提供对神经回路的洞察力，这些神经回路检测到 在奖赏缺失的初始阶段，获得奖赏并迅速调整动物的行为。

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.