Neuronal mechanisms of novelty seeking

项目总结 在人类和灵长类动物上的行为实验表明，新的视觉对象通过捕捉 注意和凝视，并促进学习。寻求新奇事物的异常与强迫症有关 强迫症、焦虑症、抑郁症、快感缺失和自闭症。但尽管新奇的物品在 我们的日常生活和寻求新奇事物的临床相关性，我们缺乏对灵长类大脑如何循环的了解 确定一个物体是否是新奇的，以及新奇的信号如何控制新奇的寻找。以前的研究报告 大脑许多区域的神经元对新的刺激和熟悉的刺激的反应是不同的。然而，小说 刺激在许多方面不同于我们熟悉的刺激。例如，新的刺激是意想不到的，偏离了 最近的经历，并激励行为。新奇事物对行为的如此广泛和多样的影响不仅 强调了解寻求新奇事物的神经机制是至关重要的，但也说明了为什么 一直在挑战将新奇信号从其他类型的神经信号中分离出来，因此为什么 很难分离出电路是如何利用新颖性来控制动机行为的。这些目标的假设是 (I)物体新颖性通过新发现的前腹内侧颞叶皮质控制新颖性寻求 (Ii)单个AVMTC神经元通过 可定量定义的算法，考虑对象新近性和对象意想性来调解新颖性- 相关行为。目标1将揭示控制动机行为的神经机制，以探索新的 物体。我们设计了一种新的行为范式，衡量猴子对体验新奇物体的渴望。 初步的神经生理学和因果实验表明，研究不足的丘脑下部区域 Za Incerta(ZI)，控制寻找和探索新的视觉对象的动机，并且这个ZI功能是 有别于其他类型的主要奖励和内在动机行为，如获得动力 关于不确定回报的信息。这些断言将通过对比 Zi与缰核-多巴胺通路有关。我们还将研究当新奇事物发生时，这个电路是如何控制新奇事物的 具有外在价值(例如，好的或坏的)，必须整合到目标评估中。目标2将决定 在灵长类动物大脑的广泛回路中通过记录单个 半慢性癫痫患者颞叶皮质、杏仁核、海马和前额叶皮质神经元的活动 高通道数阵列，而猴子参与的行为程序将(I)评估 单个神经元对象新颖性反应的基础，并将(Ii)将新颖性反应与符号分离 以及无符号主观值和预测误差。这些目标提供了一个前所未有的机会 了解大脑如何调节接近和探索新对象的好奇心，这是一个基本的 一种内在动机行为的形式，在灵长类动物中特别突出，在许多情况下是失控的 认知和情绪障碍。

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.