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

项目名称：环境和生理状态对中脑边缘奖赏编码的影响 项目摘要/摘要 奖励的编码是一个复杂的过程，它受到多种因素的调节，这些因素超出了 主要刺激功能，包括环境和环境中的上下文和离散提示之间的交互 改变到生理状态。一般来说，奖励和随后的目标导向行为的编码是 通常是适应性的，对生存是必不可少的。然而，世界各地的人类经常被轰炸 环境背景线索，可引发猖獗的不适应奖励寻求行为 肥胖和吸毒等突出的健康问题。虽然许多人已经研究了中边缘系统 在适应性和非适应性目标导向行为的镜头下，令人惊讶的是，人们对 语境线索在调节中边缘系统中的作用。此外，该组织的功能 中脑边缘系统受到生理状态的强烈调节，并可以影响中脑边缘的阶段 多巴胺反应编码特定的结果(例如，滥用的食物、水和药物)。因此，一名少校 这项提议的目的是描绘整合以下信息的神经底物 背景线索、离散线索和生理状态，它们随后引导目标- 定向行为。VTA-NAC时相多巴胺活性与目标导向密切相关 行为，并受到生理状态的强烈影响。在目标I中，我们利用体内纤维光度法在 清醒的，表现得像动物一样，从VTA多巴胺神经元产生实时记录，而动物学习 将水的可获得性与离散的线索联系起来。然后我们检查穹隆下器的口渴神经元。 (SFO)作为向VTA多巴胺神经元传递生理状态信息的主要神经底物 使用纤维光度和化学发生操作。基于之前的工作和试点数据，我们 预计SFO对于水提示诱发的VTA相的调制是必要的和充分的 多巴胺活性。我们还将确定SFO与SFO进行通信的多突触路径 VTA。在AIM II中，我们认为VTA时相多巴胺信号是生理状态和 部分由腹侧海马区(VHP)的输入调节的语境线索。这里我们使用的是光纤 VTA多巴胺神经元在一项新的行为任务中与VHP化学遗传学联合的光度学研究 在那里，动物学会将水的可用性与与缺水或缺水配对的环境联系在一起- 满足感。当水分充足时，我们预计缺水环境会增加水线索诱发的VTA 这一反应依赖于VHP介导的上下文处理。已被占用 总而言之，这些研究的新发现将使人们更好地理解目标导向是如何 行为是在大脑中获得和表达的，并提供了重要的机械数据，将 严重影响肥胖和吸毒成瘾等健康问题的治疗。]]

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.]]