Neuronal mechanisms of novelty seeking

寻求新奇的神经机制

• 批准号: 10518796
• 负责人: Ilya E. Monosov
• 金额: $ 39.38万
• 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/10518796
• 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; Dopamine; Familiarity; Habenula; Hippocampus (Brain); 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 人类和灵长类动物的行为实验表明，新奇的视觉物体通过捕捉 注意力和凝视，促进学习。对新奇事物的追求与强迫性 强迫症、焦虑症、抑郁症、快感缺乏症和自闭症。但是，尽管新奇的物品在 我们的日常生活，以及寻求新奇事物的临床相关性，我们缺乏对灵长类动物大脑回路的理解， 确定一个物体是否新奇，以及新奇信号如何控制新奇寻求。先前的研究报告 许多大脑区域的神经元对新奇刺激和熟悉刺激的反应不同。然而，小说 刺激在许多方面不同于熟悉的刺激。例如，新的刺激是意想不到的，偏离 最近的经历和激励行为。新奇事物对行为的这种广泛而多样的影响不仅 强调了理解新奇寻求的神经机制是至关重要的，但也说明了为什么它 将新奇的信号与其他类型的神经信号分离开来一直是一个挑战，因此， 很难分离出电路如何利用新奇来控制动机行为。目标的假设是， (i)客体新奇性通过新发现的前腹内侧颞叶皮层控制新奇性寻求 （ii）单个AVMTC神经元通过一个新奇的选择性， 定量定义的算法，考虑对象的新近性和对象的意外性来调解新奇， 相关行为。目的1将揭示控制动机行为的神经机制，以探索新的 对象我们设计了一种新的行为模式，来衡量猴子对新奇事物的渴望。 初步的神经生理学和因果关系实验表明，一个研究不足的丘脑底区， 大脑皮层（ZI）控制着寻找和探索新的视觉对象的动机，这种ZI功能是 与其他类型的主要奖励和内在动机行为不同，例如来自获得的驱动力 关于不确定奖励的信息。这些断言将通过对比 ZI与缰核-多巴胺通路。我们还将研究这个电路如何控制新奇寻求时， 具有外部值（例如，好的或坏的），必须纳入对象评估。目标2将决定 通过记录单一的信号，在灵长类动物的大脑回路中产生新奇反应的机制 颞叶皮层、杏仁核、海马和前额叶皮层的神经元活动 高通道计数阵列，而猴子参与行为程序，将（i）评估 单神经元的对象新奇反应的基础，并将（ii）将新奇反应与有符号的 以及无符号主观值和预测误差。这些目标提供了前所未有的机会， 了解大脑如何调解好奇心接近和探索新的物体，这是一个基本的 一种内在动机行为，在灵长类动物中特别突出，在许多动物中失调。 认知和情绪障碍。