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（由申请人提供）：与rike食物相关的环境提示可以获取动机，这是对这些目标导演的奖励行为的启动。并学到的结合。在钠剥夺状态下品尝）。 sex段面积（VTA），激活盐水提示和盐本身在钠剂量之后到pai red提示和蔗糖。 - 单独的行为和提示的估值。 ）除钠的自适应盐和盐奖励外，还包括副总裁（AIM 2）和NAC或VP（AIM 3），以揭示活动的模式如何出现。这些疾病的自适应行为和强迫性行为的神经机制。国家学习和预测模型的变化不容易通过应用新技术和行为范式来研究如何在大脑中出现这种目标变化的机制。奖励系统出现。