Neuronal mechanisms of novelty seeking

寻求新奇的神经机制

• 批准号: 10688272
• 负责人: Ilya E. Monosov
• 金额: $ 38.88万
• 依托单位: WASHINGTON UNIVERSITY
• 依托单位国家: 美国
• 财政年份: 2022
• 资助国家: 美国
• 起止时间: 2022-08-23 至 2027-06-30
• 项目状态: 未结题
• 来源: https://reporter.nih.gov/project-details/10688272
• 关键词: Algorithms; Amygdaloid structure; Anhedonia; Anterior; Anxiety; Area; Attention; Behavior; Behavioral; Behavioral Paradigm; Brain; Brain region; Chronic; Cognition; Cognition Disorders; Curiosities; Data; Detection; Dissociation; Dopamine; Familiarity; Habenula; Hippocampus; Human; Lateral; Learning; Life; Measures; Medial; Mediating; Memory; Mental Depression; Monkeys; Moods; Motivation; Nature; Neurons; Neurosciences; Obsessive-Compulsive Disorder; Pathway interactions; Population; Prefrontal Cortex; Primates; Procedures; Process; Reporting; Rewards; Signal Transduction; Stimulus; Structure; System; Temporal Lobe; Testing; Time; Visual; Work; autism spectrum disorder; clinically relevant; experience; experimental study; flexibility; forgetting; gaze; motivated behavior; neuromechanism; neurophysiology; neurotransmission; nonhuman primate; novel; response; stem; theories; zona incerta

PROJECT SUMMARY Behavioral experiments in humans and primates show that novel visual objects motivate behavior, by capturing attention and gaze, and promoting learning. Abnormalities in novelty seeking are associated with obsessive compulsive disorder, anxiety, depression, anhedonia and autism. But despite the importance of novel objects in our daily life, and the clinical relevance of novelty seeking, we lack an understanding of how primate brain circuits determine whether an object is novel, and how novelty signals control novelty-seeking. Previous studies reported that neurons in many brain areas respond differently to novel stimuli versus familiar stimuli. However, novel stimuli differ from familiar stimuli in many respects. For instance, novel stimuli are unexpected, deviate from recent experiences, and motivate behavior. Such broad and diverse impact of novelty on behavior not only highlights that it is critical to understand the neural mechanisms of novelty seeking, but also illustrates why it has been challenging to dissociate novelty signals from other types of neural signals, and therefore why it has been difficult to isolate how circuits utilize novelty to control motivated behavior. The hypotheses of the Aims are that (i) object novelty controls novelty seeking through a newly discovered anterior ventral medial temporal cortex (AVMTC) to zona incerta circuit, and (ii) single AVMTC neurons acquire novelty selectivity through a quantitatively definable algorithm that considers object recency and object unexpectedness to mediate novelty- related behaviors. Aim 1 will uncover the neural mechanisms that control motivated behavior to explore novel objects. We devised a new behavioral paradigm that measures monkeys’ eagerness to experience novel objects. Preliminary neurophysiological and causal experiments suggest that an understudied subthalamic region, the zona incerta (ZI), controls the motivation to seek and explore novel visual objects, and that this ZI function is distinct from other types of primary reward- and intrinsic- motivated behaviors, such as from the drive to obtain information about uncertain rewards. These assertions will be fully tested by contrasting the novelty functions of ZI with the habenula-dopamine pathway. We will also study how this circuit controls novelty seeking when novelty has extrinsic values (e.g., good or bad) and must be integrated into object valuation. Aim 2 will determine the mechanisms through which novelty responses arise in a wide range of primate brain circuits by recording single neurons’ activity across temporal cortex, amygdala, hippocampus, and the prefrontal cortices with semi chronic high channel count arrays while monkeys participate in a behavioral procedure that will (i) assess the underpinnings of single neurons’ object novelty responses, and will (ii) dissociate novelty responses from signed and unsigned subjective-value and prediction errors. These Aims offer an unprecedented opportunity to understand how the brain mediates the curiosity to approach and explore novel objects, which is a fundamental form of intrinsic motivated behavior that is particularly prominent in primates, and that is dysregulated in many disorders of cognition and mood.

项目摘要 人类和私人的行为实验表明，新颖的视觉对象通过捕获来动机行为 注意力和凝视，并促进学习。新颖性寻求异常与痴迷有关 强迫症，焦虑，抑郁症，痛苦和自闭症。但是尽管新颖的物体很重要 我们的日常生活以及寻求新颖性的临床相关性，我们对灵长类动物脑电路的方式缺乏了解 确定物体是否是新颖的，以及新颖的信号如何控制寻找新颖性。先前的研究报道 许多大脑区域的神经元对新型刺激与熟悉的刺激的反应不同。但是，新颖 在许多方面，刺激与熟悉的刺激不同。例如，新颖的刺激是出乎意料的，偏离 最近的经历和成熟的行为。这种新颖性的广泛和潜水对行为的影响不仅 强调了解寻求新颖性的神经机制至关重要，但也说明了为什么它具有 面临挑战以将新颖性信号与其他类型的神经信号分离，因此为什么 难以隔离电路如何利用新颖性来控制动机行为。目标的假设是 （i）物体新颖性​​控制着通过新发现的前腹侧内侧临时皮质寻求新颖性 （AVMTC）到Zona incerta电路，（ii）单个AVMTC神经元通过A获得新颖性的选择性 定义定义的算法，该算法考虑对象新颖性和物体意外性，以介导新颖性 - 相关行为。 AIM 1将发现控制动机行为以探索新颖的神经力学 对象。我们设计了一种新的行为范式，该范式衡量了猴子渴望体验新物体的渴望。 初步的神经生理学和因果实验表明，一个理解的丘脑下区域，即 Zona Incerta（Zi）控制着寻找和探索新型视觉对象的动机，并且此Zi功能是 与其他类型的主要奖励和内在动机行为不同，例如从驱动器获得 有关不确定奖励的信息。这些断言将通过对比的新颖功能来充分测试 Zi具有Habenula-Dopamine途径。我们还将研究该电路如何控制新奇 具有外在值（例如好是坏），必须集成到对象值中。 AIM 2将确定 通过记录单个单一的脑电路，新颖响应在各种元素中产生的机制 神经元在临时皮质，杏仁核，海马和带有半慢性的前额叶皮质的活动 高频道计数阵列，而猴子也参与了（i）评估的行为程序 单个神经元对象新颖性反应的基础，并将（ii）与签名的新颖性反应分离 以及未签名的主观值和预测错误。这些目标为前所未有的机会 了解大脑如何介导好奇心接近和探索新颖对象，这是一个基本 在私人中特别突出的内在动机行为的形式，在许多人中都失调 认知和情绪障碍。