Amygdala Encoding of Reward Memory

奖励记忆的杏仁核编码

• 批准号: 10437637
• 负责人: Baila Sara Hall
• 金额: $ 4.05万
• 依托单位: UNIVERSITY OF CALIFORNIA LOS ANGELES
• 依托单位国家: 美国
• 财政年份: 2021
• 资助国家: 美国
• 起止时间: 2021-07-01 至 2023-01-03
• 项目状态: 已结题
• 来源: https://reporter.nih.gov/project-details/10437637
• 关键词: Adaptive Behaviors; Amygdaloid structure; Basic Science; Behavioral; Behavioral Assay; Behavioral Mechanisms; Calcium; Cannabis; Cells; Choice Behavior; Coupled; Cues; Data; Decision Making; Desire for food; Disease; Drug Targeting; Emotional; Environment; Event; Foundations; Future; Genetic Recombination; Goals; Image; Immunohistochemistry; Individual; Intervention; Learning; Life; Literature; Memory; Mentors; Microscope; Mus; Neurobiology; Neurons; Neurosciences; Opioid; Outcome; Pattern; Population; Process; Psyche structure; Research; Resolution; Rewards; Role; Running; Sensory; Site; Stimulant; Stimulus; Substance Use Disorder; Support System; System; Testing; Training; Transgenic Mice; Work; addiction; approach behavior; avoidance behavior; base; career; classical conditioning; design; drug of abuse; experience; experimental study; in vivo; in vivo calcium imaging; insight; maladaptive behavior; miniaturize; neural circuit; neuromechanism; neuropsychiatry; novel; optogenetics; relating to nervous system; response; simulation; theories; tool; treatment strategy

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.

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。这些考虑是根据我们对1949年类似情况的记忆而得出的。 过去这种能力在包括物质使用在内的许多神经精神疾病中被破坏 disorder.做出适应性决策的一种行为机制是通过刺激-奖励 协会.尽管理解适应性决策和不适应性决策的重要性， 对编码这些刺激奖励记忆的神经回路知之甚少。因此，将军 这个项目的目标是评估刺激奖励记忆的神经机制，以及它们是如何 影响决策。这项工作将提供深入了解动机决策的一个重要方面， 了解这些过程在疾病状态下如何出错的基础，并最终告知 治疗策略。 一个新兴的文献表明，记忆可以编码在离散的神经集合。这些 在基底外侧杏仁核中也发现了细胞群，这是一个神经区域， 奖励记忆的编码和提取。然而，我们对合奏是否以及如何合奏的理解 基底外侧杏仁核中的细胞代表独特的奖励，线索，并随后指导决策， 不完整我提出的研究将确定是否有独特的奖励和线索代表细胞， 以及它们如何促进选择行为。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测定。在目标1中，我将 利用一种新的标记和捕获方法来操纵基底外侧的奖励和提示激活神经元 杏仁核来确定这些神经集合对决策的因果贡献。在目标2中，我将 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， 基底外侧杏仁核对奖励及其附属线索的反应，以及决策过程。成果 这些拟议的实验将为我们理解基底外侧如何提供关键信息。 杏仁核有助于奖励有动机的选择。这些发现也将为如何在 基底外侧杏仁核可能是药物滥用的靶点，但也可能是干预的部位 和治疗。我将在加州大学洛杉矶分校的Wassum实验室进行这些研究，并得到一位 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。这将使我有能力实现我的职业目标， 研究成瘾神经生物学的独立研究实验室