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: 9244066
• 负责人: Stephen Chang
• 金额: $ 5.92万
• 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/9244066
• 关键词: Affect; Attenuated; Behavior; Behavioral; Behavioral Paradigm; Brain; Clinical; Compulsive Behavior; Cues; Decision Making; Desire for food; Development; Disease; Dopamine; Employee Strikes; Exposure to; Food; Foundations; Functional disorder; Globus Pallidus; Goals; Human; Intervention; Knowledge; Lead; Learning; Measures; Memory; Mental Depression; Modeling; Motivation; Neuronal Dysfunction; Neurons; Nucleus Accumbens; Obesity; Pathway interactions; Pattern; Pharmaceutical Preparations; Process; Property; Psychological reinforcement; Rattus; Reaction; Research; Rewards; Rodent; Role; Sodium; Sodium Chloride; 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; experience; hedonic; indexing; insight; 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（由适用提供）：与食物之类的奖励相关的环境提示可以自己获得动机价值，从而在随后的提示演讲后产生了寻求奖励行为的倡议。这些目标指导的行为不是通过逐步的反复学习学习来获得的，而是由于当前状态与学识渊博的关联之间的相互作用而产生的。一个关键的例子是“盐食欲”。已经学会了将提示与厌恶浓缩的盐味相关联的大鼠，如果钠耗尽钠，甚至在盐经历了阳性之前，就会响应提示并寻找盐。关于提示和目标如何在发生预测误差之前（即，何时在钠剥落状态下首次处理盐）之前，知之甚少。拟议的研究将使用这种引人注目的现象作为模型来研究自适应盐寻求盐行为的神经回路。先前的工作表明，腹侧颗粒（VP）的神经元在双向连接到其他奖励电路区域，包括伏隔核（NAC）和腹侧细盖区域（VTA），以与含含糖含量的提高含量的含钠剥夺后，激活了盐型提示和盐本身。尽管这些VP神经元动力学与提示和奖励的行为相关的变化相关，但尚不清楚VP动力学是否对于寻求盐的行为是必需的，也不是NAC和多巴胺对VP的投入如何调节其活性和提示的价值。拟议的研究将使用光遗传学工具，新病毒载体和转基因TH-CRE大鼠来研究临时抑制VP（AIM 1），NAC-VP途径（AIM 2）和多巴胺能VTA对NAC或VP（AIM 3）对适应性盐分脱盐行为剥夺的影响。此外，AIM 2和3还包括VP（AIM 2）和NAC或VP（AIM 3）的简单四极记录，以发现与目标寻求目标相关的活动模式。拟议的研究将提供有关自适应目标行为的神经机制的新见解，并可以大大介意我们对奖励功能障碍（包括抑郁症，肥胖和强迫性行为）的疾病的理解。这些疾病的特征是对线索和动机问题的反应性无反应性，并且被认为涉及VTA-NAC-VP功能障碍。此外，由于状态变化（例如压力或药物启动）的变化，这种问题通常会出现，这一功能不容易通过当前的增量学习和预测 - 错误模型来解释。通过应用新技术和行为范式来研究大脑中这种守门员的直接变化如何发生的机制，该作品具有巨大的潜力，可以更新我们对奖励系统疾病的理解。