Amygdala Encoding of Reward Memory

为了做出适应性的目标导向的选择，我们必须考虑我们行为的后果，这样我们才能选择 最有利的选择。这些考虑是由我们对类似情况的记忆在 过去的事。这种能力在许多神经精神疾病中被破坏，包括物质使用 无序。做出适应性决策的一种行为机制是通过刺激-奖励 联想。尽管理解适应性和非适应性决策很重要，但我们 对编码这些刺激-奖赏记忆的神经回路知之甚少。因此，这位将军 这个项目的目标是评估刺激-奖赏记忆背后的神经机制以及它们是如何 影响决策。这项工作将提供对激励决策的一个重要方面的洞察，即设定 这是了解这些过程在疾病状态下如何出错并最终告知 治疗策略。 一篇新兴的文献表明，记忆可以在离散的神经集合中进行编码。这些 在基底外侧杏仁核也发现了大量的细胞，杏仁核是一个同样重要的神经区域 涉及到奖励记忆的编码和检索。然而，我们对是否以及如何进行合奏的理解 杏仁核基底外侧区细胞的数量代表独特的奖赏、提示，并随后指导决策 不完整。我提议的研究将确定是否存在代表细胞的唯一奖励和线索 杏仁基底外侧核及其如何促进选择行为。为了实现这些目标，我将使用 结合尖端的神经科学工具和复杂的小鼠行为分析。在《目标1》中，我将 利用一种新的标记和捕捉方法来操纵基底外侧区激活的奖赏和提示神经元 杏仁核，以确定这些神经集合对决策的因果贡献。在《目标2》中，我会 通过微型显微镜使用体内细胞分辨率钙成像来揭示神经动力学 杏仁基底外侧核对奖赏及其相关线索的反应，以及在决策过程中的反应。结果是 这些拟议的实验将为我们理解基侧向如何 杏仁核有助于奖励动机的选择。这些发现还将为我们提供关于 杏仁基底外侧核可能是药物滥用的目标，但也可能是干预的场所。 和治疗。我将在加州大学洛杉矶分校的沃森实验室进行这些研究，并得到一个 多元化和全面的指导团队。加州大学洛杉矶分校的环境也将提供优秀的智力， 技术和专业培训。这将使我有充分的准备来实现我的职业目标，即经营一家 研究成瘾神经生物学的独立研究实验室。

To made adaptive goal-directed choices, we have to consider the consequences of our actions so we can select the most advantageous choice. These considerations are informed by our memory of similar circumstances in the past. This capacity becomes disrupted in many neuropsychiatric conditions including substance use disorder. One behavioral mechanism by which adaptive decisions are made is via stimulus-reward associations. Despite the importance of understanding both adaptive and maladaptive decision making, we know very little about the neural circuits that encode these stimulus-reward memories. As such, the general goal of this project is to evaluate the neural mechanisms that underlie stimulus-reward memories and how they influence decision making. This work will provide insight into a vital aspect of motivated decision making, setting a foundation for understanding how these processes may go awry in disease states, and ultimately inform treatment strategies. A burgeoning literature indicates that memories can be encoded in discrete neural ensembles. These populations of cells have also been identified in the basolateral amygdala, a neural region that is also essential to the encoding and retrieving of reward memories. However, our understanding of whether and how ensembles of cells in the basolateral amygdala represent unique rewards, cues, and subsequently guide decisions is incomplete. My proposed study will determine whether there are unique reward and cue representing cells in the basolateral amygdala and how they may promote choice behavior. To accomplish these goals I will use a combination of cutting edge neuroscience tools and sophisticated behavioral assays in mice. In Aim 1, I will utilize a novel tag and capture approach to manipulate reward and cue activated neurons in the basolateral amygdala to determine the causal contribution of these neural ensembles to decision making. In Aim 2, I will use in vivo cellular resolution calcium imaging via miniaturized microscopes to reveal the neural dynamics of the basolateral amygdala in response to rewards and their affiliative cues, and during decisions. The outcomes of these proposed experiments will provide crucial information for our understanding of how the basolateral amygdala contributes to reward motivated choice. These findings will also provide insight for how the basolateral amygdala might be a target for drugs of abuse, but also may also serve as a site for intervention and treatment. I will carry out these studies in the Wassum Lab at UCLA, with the support and direction of a diverse and well-rounded mentoring team. The environment at UCLA will also provide excellent intellectual, technical and professional training. This will leave me well equipped to achieve my career goals of running an independent research lab studying addiction neurobiology.