Neural Mechanisms of Adaptive Reward Seeking and Salt Appetite

适应性奖励寻求和盐食欲的神经机制

• 批准号: 8908632
• 负责人: Stephen Chang
• 金额: $ 5.24万
• 依托单位: DARTMOUTH COLLEGE
• 依托单位国家: 美国
• 财政年份: 2015
• 资助国家: 美国
• 起止时间: 2015-04-01 至 2018-03-31
• 项目状态: 已结题
• 来源: https://reporter.nih.gov/project-details/8908632
• 关键词: Affect; Association Learning; Attenuated; Base of the Brain; Behavior; Behavioral Paradigm; Brain; Canned Foods; Clinical; Compulsive Behavior; Cues; Decision Making; Desire for food; Development; Disease; Dopamine; Employee Strikes; Exposure to; Foundations; Functional disorder; Globus Pallidus; Goals; Human; Intervention; Knowledge; Lead; Learning; Left; Measures; Memory; Mental Depression; Modeling; Motivation; Neurons; Nucleus Accumbens; Obesity; Pathway interactions; Pattern; Pharmaceutical Preparations; Process; Property; Psychological reinforcement; Rattus; Reaction; Research; Rewards; Rodent; Role; Sodium; Sodium Chloride; Solutions; Stress; Sucrose; System; Taste Perception; Techniques; Testing; Therapeutic Intervention; Time; Transgenic Organisms; Update; Ventral Tegmental Area; Viral Vector; Work; addiction; cue reactivity; deprivation; dopaminergic neuron; drinking; driving behavior; experience; hedonic; indexing; insight; meetings; motivational processes; neural circuit; neuromechanism; new technology; novel; optogenetics; orofacial; preference; public health relevance; relating to nervous system; response; reward circuitry; sugar; tool

 DESCRIPTION (provided by applicant): Environmental cues associated with rewards like food can acquire motivational value themselves, resulting in the initiation of reward-seeking behaviors upon subsequent cue presentations. These goal-directed behaviors are not acquired through incremental trial-and-error learning, but arise from an interaction between current states and learned associations. A key example is "salt appetite". Rats that have learned to associate a cue with an aversively concentrated salt taste will respond to the cue and seek out salt if they are sodium-depleted, even before salt has ever been experienced as positive. Little is known about how cues and goals can acquire value in such a drastic manner before a prediction error can occur (i.e., when salt is first tasted in a sodium-deprived state). The proposed research will investigate the neural circuitry of adaptive salt-seeking behavior using this striking phenomenon as a model. Previous work has shown that neurons of the ventral pallidum (VP), which is bidirectionally connected to other reward circuit regions including the nucleus accumbens (NAc) and ventral tegmental area (VTA), activate to salt-paired cues and salt itself following sodium deprivation in a similar manner to sucrose-paired cues and sucrose. Although these VP neural dynamics correlate with the behaviorally-relevant shifts in the value of cues and rewards, it is unknown whether VP dynamics are necessary for salt-seeking behavior, nor how NAc and dopamine inputs to VP regulate its activity and the valuation of cues. The proposed studies will use optogenetic tools, new viral vectors, and transgenic TH-Cre rats to investigate the effects of temporarily inhibiting VP (Aim 1), the NAc-VP pathway (Aim 2), and dopaminergic VTA inputs to NAc or VP (Aim 3) on adaptive salt-seeking behavior and salt reward following sodium deprivation. In addition, Aims 2 and 3 include simultaneous tetrode recordings of VP (Aim 2) and NAc or VP (Aim 3) to uncover how patterns of activity related to goal seeking arise. The proposed studies will provide fresh insight into the neural mechanisms of adaptive goal-seeking behaviors, and could substantially update our understanding of disorders of reward dysfunction including depression, obesity, and compulsive behaviors. These disorders are characterized by hypo- or hyper-reactivity to cues and motivational problems, and are thought to involve VTA-NAc-VP dysfunction. Moreover, such problems often arise as immediate changes in motivation due to a change in state, such as stress or drug priming, a feature not easily explained by current incremental learning and prediction-error models. By applying new techniques and behavioral paradigms to study mechanisms of how such immediate changes in goal-seeking occur in the brain, the work carries great potential for updating our understanding of how disorders of the reward system arise.

 描述（由申请人提供）：与奖励（如食物）相关的环境线索本身可以获得激励价值，导致在随后的线索呈现时启动寻求奖励的行为。这些目标导向的行为不是通过渐进式试错学习获得的，而是从当前状态和学习到的联想之间的相互作用中产生的。一个关键的例子是“盐的胃口”。已经学会将暗示与令人厌恶的浓盐味道联系起来的老鼠会对暗示做出反应，如果它们钠耗尽，甚至在盐被体验为阳性之前，它们就会寻找盐。很少有人知道线索和目标如何在预测错误发生之前以如此激烈的方式获得价值（即，当在钠缺乏状态下首次品尝盐时）。这项拟议中的研究将以这种惊人的现象为模型，研究适应性盐寻求行为的神经回路。以前的工作表明，腹侧苍白球（VP）的神经元，这是双向连接到其他奖励电路区域，包括核丘脑（NAc）和腹侧被盖区（VTA），激活盐配对的线索和盐本身钠剥夺类似的方式蔗糖配对的线索和蔗糖。虽然这些VP神经动力学与行为相关的线索和奖励的价值的变化，它是未知的VP动力学是否是必要的盐寻求行为，也不知道如何NAC和多巴胺输入VP调节其活动和线索的估值。拟议的研究将使用光遗传学工具，新的病毒载体和转基因TH-Cre大鼠来研究暂时抑制VP（Aim 1），NAc-VP通路（Aim 2）和多巴胺能VTA输入NAc或VP（Aim 3）对钠剥夺后适应性盐寻求行为和盐奖励的影响。此外，目标2和3包括VP（目标2）和NAc或VP（目标3）的同时四极记录，以揭示与目标寻求相关的活动模式如何出现。这些研究将为适应性目标寻求行为的神经机制提供新的见解，并可能大大更新我们对奖励功能障碍的理解，包括抑郁症，肥胖症和强迫行为。这些疾病的特征是对线索和动机问题的低反应性或高反应性，并被认为涉及VTA-NAc-VP功能障碍。此外，这些问题通常是由于状态的变化而引起的动机的立即变化，例如压力或药物启动，这一特征不容易用当前的增量学习和预测误差模型来解释。通过应用新的技术和行为范式来研究大脑中目标寻求的这种即时变化是如何发生的，这项工作具有很大的潜力，可以更新我们对奖励系统紊乱是如何产生的理解。