Frontocortical representations of amygdala-mediated learning under uncertainty

不确定性下杏仁核介导的学习的额皮质表征

基本信息

批准号：
10825354
负责人：
Juan Luis Romero Sosa
金额：
$ 4万
依托单位：
UNIVERSITY OF CALIFORNIA LOS ANGELES
依托单位国家：
美国
项目类别：
财政年份：
2024
资助国家：
美国
起止时间：
2024-01-01 至 2025-12-31
项目状态：
未结题

来源：
https://reporter.nih.gov/project-details/10825354
关键词：
Agitation Amygdaloid structure Animal Experimentation Anterior Area Behavior Behavioral Bilateral Bipolar Disorder Brain Brain region Calcium Cells Cognition Collaborations Corpus striatum structure Data Decision Making Detection Discrimination Learning Dura Mater Engineering Environment Failure Feedback Future Genetic Goals Histologic Image Implant Individual Learning Link Measures Mediating Mental Health Mental disorders Neurons Operative Surgical Procedures Photons Population Prefrontal Cortex Primates Probability Probability Learning Rattus Resolution Reversal Learning Rewards Rodent Role Sagittal Sinus Schedule Schizophrenia Signal Transduction Stimulus Structure Symptoms System Techniques Testing Time Training Transfection Uncertainty United States National Institutes of Health Update Viral Visit Work adaptive learning arm aspirate calcium indicator cingulate cortex designer receptors exclusively activated by designer drugs expectation experience experimental study flexibility image processing implantation lens lens cortex neural neuromechanism neuropsychiatry novel recruit tool touchscreen

项目摘要

Project Abstract Learning is one of the essential building blocks of cognition. Individuals with mental health conditions, such as bipolar disorders and schizophrenia, often show symptoms related to learning. A great deal of evidence exists indicating that the orbitofrontal cortex (OFC) and anterior cingulate cortex (ACC) are both heavily involved in flexible learning under uncertainty, with the basolateral amygdala (BLA) sending robust bidirectional connections to both cortical structures. I hypothesize that BLA provides OFC and ACC with dissociable signals that delineate a difference in the expected reward and what was received, vital information for adaptive learning. In Aim 1, rats will be tested on a novel, dynamic, restless bandit task for flexible learning under different probabilistic schedules where the reward contingencies switch within the session. While rats perform this task in some sessions, we will chemogenetically inhibit BLA. A subset of these rats will also express GCaMP6f in OFC and GRIN lenses directly in this region so that we can use miniscopes to record calcium traces while the freely-moving rat learns. In parallel Aim 2, rats learning on the same task will instead have BLA on- or off-line while I record calcium traces in ACC. These approaches will allow us to study how the uncertainty representations in OFC and ACC differentially depend on BLA input. My central hypothesis is that OFC and ACC use BLA-supplied information differently: OFC receives information from BLA that is needed to detect first reversals and setting future adjustments, whereas ACC uses information from BLA to approximate changes in probabilities over time.

项目摘要学习是认知的重要组成部分之一。有心理健康问题的人，例如双相情感障碍和精神分裂症通常表现出与学习相关的症状。存在大量证据表明眶额皮层（OFC）和前扣带皮层（ACC）都严重参与不确定性下的灵活学习，基底外侧杏仁核 (BLA) 发送强大的双向信号与两个皮质结构的连接。我假设 BLA 为 OFC 和 ACC 提供可分离信号描绘了预期奖励和收到的奖励之间的差异，这是适应性的重要信息学习。在目标 1 中，老鼠将接受一项新颖的、动态的、不安分的老虎机任务的测试，以便在奖励意外事件在会话内切换的不同概率计划。当老鼠表演时在某些会话中，我们将通过化学遗传学方法抑制 BLA。这些老鼠的一部分也会表达 OFC 和 GRIN 镜片中的 GCaMP6f 直接位于该区域，以便我们可以使用微型显微镜记录钙当自由移动的老鼠学习时，就会留下痕迹。在并行的目标 2 中，学习相同任务的老鼠将会当我在 ACC 中记录钙痕迹时，BLA 在线或离线。这些方法将使我们能够研究如何 OFC 和 ACC 中的不确定性表示不同地取决于 BLA 输入。我的中心假设是 OFC 和 ACC 使用 BLA 提供的信息的方式不同：OFC 从 BLA 接收信息，这些信息需要检测第一个逆转并设置未来的调整，而 ACC 使用 BLA 的信息来近似概率随时间的变化。