The effects of context and physiological state on mesolimbic encoding of reward

环境和生理状态对中脑边缘奖励编码的影响

• 批准号: 9757507
• 负责人: Ted Hsu
• 金额: $ 6.61万
• 依托单位: UNIVERSITY OF ILLINOIS AT CHICAGO
• 依托单位国家: 美国
• 财政年份: 2019
• 资助国家: 美国
• 起止时间: 2019-06-20 至 2022-06-19
• 项目状态: 已结题
• 来源: https://reporter.nih.gov/project-details/9757507
• 关键词: Animals; Attention; Behavior; Behavioral; Brain; Complex; Critical Pathways; Cues; Data; Dopamine; Drug Addiction; Environment; Exhibits; Experimental Water Deprivation; Feeding behaviors; Fiber; Food; Glutamates; Goals; Health; Hippocampus (Brain); Human; Hunger; Hypothalamic structure; Incentives; Knowledge; Lateral; Learning; Light; Measures; Mediating; Modeling; Neighborhoods; Neurons; Obesity; Outcome; Pathway interactions; Pharmaceutical Preparations; Phase; Photometry; Physiological; Process; Rattus; Relapse; Rewards; Role; Satiation; Services; Signal Transduction; Societies; Stimulus; Structure of terminal stria nuclei of preoptic region; Subfornical Organ; Synapses; Testing; Thirst; Time; Training; Water; Water consumption; Work; awake; base; billboard; classical conditioning; cost; designer receptors exclusively activated by designer drugs; detector; dopaminergic neuron; drug of abuse; effective therapy; goal oriented behavior; in vivo; innovation; lens; mesolimbic system; motivated behavior; neurobiological mechanism; novel; obesogenic; recruit; relating to nervous system; response

Project title: The effects of context and physiological state on mesolimbic encoding of reward PROJECT SUMMARY/ABSTRACT The encoding of reward is a complex process that is regulated by a variety of factors that extend beyond primary stimulus features to include interactions between contextual and discrete cues in the environment and changes to physiological state. In general, the encoding of reward and subsequent goal-oriented behaviors are often adaptive and essential for survival. However, humans world-wide are often bombarded with environmental contextual cues that can trigger maladaptive reward-seeking behaviors that are rampant in prominent health issues like obesity and drug addiction. While many have studied the mesolimbic system under the lens of both adaptive and maladaptive goal-directed behaviors, surprisingly little is known about the contribution of contextual cues in modulating the mesolimbic system. Moreover, the functions of the mesolimbic system are powerfully modulated by physiological state and can influence how mesolimbic phasic dopamine responses encode particular outcomes (e.g. food, water, and drugs of abuse). [[Thus, a major aim of this proposal is to delineate the neural substrates that integrate information about contextual cues, discrete cues, and physiological state, which subsequently guide goal- oriented behaviors. VTA-NAc phasic dopamine activity has been strongly implicated in goal-directed behaviors and is robustly influenced by physiological state. In Aim I, we utilize in vivo fiber photometry in awake, behaving animals to generate real-time recordings from VTA dopamine neurons while animals learn to associate water availability with discrete cues. We then examine the thirst neurons of the subfornical organ (SFO) as a primary neural substrate that relays physiological state information to VTA dopamine neurons using fiber photometry and chemogenetic manipulations. Based on previous work and pilot data, we anticipate that the SFO is necessary and sufficient for the modulation of water-cue evoked VTA phasic dopamine activity. We will also determine the multi-synaptic path by which the SFO communicates with the VTA. In Aim II, we consider VTA phasic dopamine signaling as an integrator of both physiological state and contextual cues that is in part modulated by input from the ventral hippocampus (vHP). Here we use fiber photometry in VTA dopamine neurons in conjunction with vHP chemogenetics during a novel behavioral task where animals learn to associate water availability with contexts paired with either water-deprivation or water- satiation. When water-satiated, we expect water-deprivation contexts to augment water-cue evoked VTA phasic dopamine signaling and that this response is dependent on vHP mediated context processing. Taken together, the novel findings from these studies will allow for a greater understanding of how goal-directed behaviors are acquired and expressed within the brain and provide important mechanistic data that will strongly impact the treatment of health issues such as obesity and drug addiction.]]

项目名称：情境和生理状态对中脑边缘奖赏编码的影响 项目总结/摘要 奖赏的编码是一个复杂的过程，受到各种因素的调节， 主要刺激特征包括环境中上下文和离散线索之间的相互作用， 生理状态的变化。一般来说，奖励的编码和随后的目标导向行为是 通常是适应性的，是生存所必需的。然而，全世界的人类经常受到 环境背景线索，可以触发适应不良的奖励寻求行为， 肥胖和毒瘾等突出的健康问题。虽然许多人研究了中脑边缘系统 在适应性和适应不良的目标导向行为的透镜下，令人惊讶的是， 背景线索在调节中脑边缘系统中的作用。此外， 中脑边缘系统受到生理状态的强烈调节，并可影响中脑边缘系统的相位 多巴胺反应编码特定的结果（例如食物、水和滥用的药物）。[详细] 该建议的目的是描绘整合以下信息的神经基质： 背景线索，离散线索，和生理状态，随后引导目标- 导向行为。VTA-NAc阶段性多巴胺活性与目标导向的 行为，并受到生理状态的强烈影响。在目的I中，我们利用体内纤维光度法， 唤醒，行为动物产生从腹侧被盖区多巴胺神经元的实时记录，而动物学习， 将水的可用性与离散线索联系起来。然后我们检查穹窿下器官的口渴神经元 (SFO)作为将生理状态信息传递给腹侧被盖区多巴胺神经元的初级神经基质 使用纤维光度法和化学遗传学操作。基于以前的工作和试点数据，我们 预期SFO对于水提示诱发的VTA相位调制是必要和充分的 多巴胺活性我们还将确定SFO与神经元通信的多突触路径。 VTA。在目的II中，我们认为腹侧被盖区阶段性多巴胺信号是生理状态和 背景线索，部分由腹侧海马体（vHP）的输入调制。这里我们用纤维 在一种新的行为任务中，腹侧被盖区多巴胺神经元的光度测定与vHP化学遗传学联合 在那里，动物学会了将水的可用性与缺水或缺水的环境联系起来， 饱食当水饱和时，我们预期水剥夺环境会增强水线索诱发的VTA 阶段性多巴胺信号传导，并且这种反应依赖于vHP介导的背景处理。采取 总之，这些研究的新发现将使我们更好地理解目标导向是如何实现的。 行为是在大脑中获得和表达的，并提供了重要的机械数据， 强烈影响肥胖和药物成瘾等健康问题的治疗。