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.

项目概要 人类和灵长类动物的行为实验表明，新颖的视觉对象通过捕捉 注意力和凝视以及促进学习的异常与强迫症有关。 强迫症、焦虑症、抑郁症、快感缺乏症和自闭症，尽管新奇的物体很重要。 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了解 确定一个物体是否新颖，以及新颖信号如何控制新颖性寻求。 许多大脑区域的神经元对新刺激和熟悉刺激的反应不同。 刺激在许多方面与熟悉的刺激不同，例如，新奇的刺激是意想不到的、偏离的。 新奇事物不仅对最近的经历以及动机行为产生广泛而多样的影响。 强调理解寻求新奇的神经机制至关重要，同时也说明了为什么它具有 将新奇信号与其他类型的神经信号区分开来一直是一项挑战，因此为什么它一直如此 很难分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​​通过新发现的前腹内侧颞叶皮层控制新颖性寻求 （AVMTC）到未定带电路，并且（ii）单个 AVMTC 神经元通过 定量定义的算法，考虑对象的新近度和对象的意外性来调节新颖性- 目标 1 将揭示控制动机行为以探索新颖的神经机制。 我们设计了一种新的行为范式来衡量猴子体验新物体的渴望。 初步的神经生理学和因果实验表明，一个未被充分研究的底丘脑区域， 不确定带（ZI），控制寻找和探索新视觉对象的动机，并且该 ZI 功能是 与其他类型的主要奖励行为和内在动机行为不同，例如获得的驱动力 有关不确定奖励的信息。这些断言将通过对比新颖性函数来得到充分检验。 ZI 与缰核-多巴胺通路我们还将研究该电路如何控制新奇寻求。 具有外在价值（例如，好或坏），并且必须整合到对象评估中，目标 2 将确定。 通过记录单个灵长类动物大脑回路，新奇反应产生的机制 半慢性时间跨颞叶皮质、杏仁核、海马体和前额叶皮质的神经元活动 高通道数阵列，而猴子参与行为程序，该程序将（i）评估 单个神经元的对象新奇反应的基础，并且将（ii）将新奇反应与有符号的反应分离 以及未签名的主观价值和预测错误。这些目标提供了前所未有的机会。 了解大脑如何调节好奇心以接近和探索新奇的物体，这是一个基本的 内在动机行为的形式，在灵长类动物中尤为突出，并且在许多动物中失调 认知和情绪障碍。