NEURAL CIRCUITS MEDIATING UNCERTAINTY AND THEIR EFFECT ON BEHAVIOR

调节不确定性的神经回路及其对行为的影响

• 批准号: 9310909
• 负责人: Ilya E. Monosov
• 金额: $ 38.13万
• 依托单位: WASHINGTON UNIVERSITY
• 依托单位国家: 美国
• 财政年份: 2017
• 资助国家: 美国
• 起止时间: 2017-02-15 至 2021-11-30
• 项目状态: 已结题
• 来源: https://reporter.nih.gov/project-details/9310909
• 关键词: Address; Affect; Anatomy; Anxiety; Area; Behavior; Behavior Control; Behavioral; Behavioral Mechanisms; Brain; Cell Nucleus; Choice Behavior; Code; Cognition; Corpus striatum structure; Data; Decision Making; Disease; Dorsal; Drug Addiction; Emotional; Emotions; Evaluation; Event; Future; Globus Pallidus; Human; Internal Capsule; Lateral; Lead; Learning; Light; Medial; Mediating; Mental Depression; Mental disorders; Monitor; Monkeys; Moods; Motivation; Neurons; Outcome; Pharmacology; Play; Population; Primates; Process; Regulation; Reporting; Research; Rewards; Risk; Role; Signal Transduction; Source; Sum; Testing; Uncertainty; addiction; basal forebrain; base; experience; experimental study; flexibility; interest; neural circuit; neuropsychiatric disorder; novel; preference; reward anticipation

Project Summary We live in an uncertain world in which events and outcomes are often unpredictable. Being able to flexibly modify our behavior based on our uncertainty about important future outcomes, such as rewards, is critical for survival. Many studies have reported that reward uncertainty modulates behavioral and emotional states, and that improper evaluation of uncertainty is associated with maladaptive behaviors, such as risk-seeking, anxiety, and addiction. Recent evidence suggests that within the brain there are populations of neurons devoted to signaling uncertainty. But how this signal is broadcast and utilized is unknown. We will test the hypothesis that the basal forebrain (BF) plays a major role in broadcasting this signal. We will further test the idea that medial and dorsal-lateral subregions of BF differentially contribute to the regulation of behavior in uncertain contexts. In Aim 1, we will test whether and how different subregions of the primate BF signal and combine information about uncertainty and value. The medial BF is thought to be crucial for learning and monitoring of important events, and dorsal-lateral portions of the BF, known as the ventral pallidum or the ventral-rostral globus pallidus, are thought to regulate motivation. If this is true, then it seems likely that these two BF subregions might represent uncertainty in very different ways. Next, we propose to examine how the differential representations of uncertainty and value in different regions of the BF contribute to behavior. If dorsal-lateral BF regulates motivation, then it is possible that uncertainty-signals there modulate uncertainty-related behaviors, such as risk-seeking. To test this hypothesis, we will study BF activity while monkeys choose between certain and uncertain rewards. Preliminary data support the hypothesis that dorsal-lateral BF's uncertainty representation is correlated with risky-choices, while medial BF's uncertainty signals emerge after the risky choice, while the subject awaits the choice-outcome. Finally, we will transiently inactivate different subregions of BF to causally test how the differential neuronal encoding of uncertainty in those regions contributes to choice behavior. In Aim 2 we will test whether a major input to the dorsal-lateral BF, the striatum, is a source of the uncertainty signal we observed there. Based on data gathered during preliminary experiments, we hypothesize that uncertainty coding neurons clustered in the internal capsule bordering region of the striatum could be the source of uncertainty modulation observed in dorsal-lateral BF. To causally test this hypothesis, the last experiment in Aim 2 will assess whether inactivation of this striatal area reduces the uncertainty sensitivity of neurons in the BF. Uncertainty about rewards modulates motivation and decision making. Our proposed experiments will provide crucial information about the neuronal mechanisms of behavioral modulation by uncertainty. Understanding these mechanisms in primates provides a crucial linkage to understanding human neuropsychiatric diseases.

项目摘要 我们生活在一个不确定的世界，其中的事件和结果往往是不可预测的。能够灵活地 根据我们对未来重要结果(如奖励)的不确定性来调整我们的行为，对于 生死存亡。许多研究报告称，奖励的不确定性会调节行为和情绪状态，并且 对不确定性的不当评估与不适应行为有关，如寻求风险、焦虑、 还有毒瘾。最近的证据表明，在大脑中，有大量的神经元致力于 发出不确定的信号。但这种信号是如何传播和利用的还不得而知。我们将检验这一假设 基底前脑(BF)在传递这一信号方面起着重要作用。我们将进一步检验这样一种观点，即医疗 而BF背侧亚区对不确定环境下的行为调控有不同的贡献。 在目标1中，我们将测试灵长类动物BF的不同亚区是否以及如何结合信息 关于不确定性和价值。内侧BF被认为对学习和监测重要的 事件和BF的背外侧部分，称为腹侧苍白球或腹头端球 苍白球被认为是调节动机的。如果这是真的，那么这两个BF亚区似乎很可能 可能以非常不同的方式代表不确定性。接下来，我们建议研究一下差异是如何 高炉不同地区的不确定性和价值的表现促成了行为。如果背侧 BF调节动机，那么那里的不确定性信号就有可能调制与不确定性相关的 行为，如寻求风险。为了验证这一假设，我们将研究BF的活动，同时猴子选择 在确定和不确定的回报之间。初步数据支持这样一种假设，即背侧高炉 不确定性表征与风险选择相关，而中间高炉的不确定性信号出现在 风险选择，而主体等待选择--结果。最后，我们将暂时停用不同的 BF亚区因果关系测试这些区域的不确定差异神经元编码 有助于选择行为。在目标2中，我们将测试背侧BF的一个主要输入是否 纹状体是我们在那里观察到的不确定信号的来源。基于在初步调查期间收集的数据 实验中，我们假设不确定性编码神经元聚集在内囊交界区 纹状体的变化可能是在背侧BF观察到不确定调制的来源。进行因果检验 这一假设是目标2中的最后一个实验，它将评估纹状体区域的失活是否会减少 高炉内神经元的不确定性敏感性。 报酬方面的不确定性会影响动机和决策。我们提议的实验将提供 关于不确定性调节行为的神经机制的关键信息。理解 灵长类动物的这些机制为理解人类神经精神疾病提供了至关重要的联系。