The role of novelty and surprise in aversive conditioning

新奇和惊喜在厌恶性条件反射中的作用

• 批准号: 10682277
• 负责人: Brian J Wiltgen
• 金额: $ 58.15万
• 依托单位: UNIVERSITY OF CALIFORNIA AT DAVIS
• 依托单位国家: 美国
• 财政年份: 2023
• 资助国家: 美国
• 起止时间: 2023-08-01 至 2027-07-31
• 项目状态: 未结题
• 来源: https://reporter.nih.gov/project-details/10682277
• 关键词: Address; Alzheimer' s Disease; American; Amnesia; Animals; Anxiety; Anxiety Disorders; Association Learning; Atrophic; Attention deficit hyperactivity disorder; Auditory; Aversive Stimulus; Bipolar Disorder; Brain; Catecholamines; Cues; Data; Disease; Dopamine; Dopamine Antagonists; Dopamine Receptor; Dorsal; Electrophysiology (science); Emotional disorder; Environment; Event; Extinction; Food; Fright; Future; Genetic; Goals; Hippocampus; Hour; Human; Impairment; Learning; Life; Memory; Memory impairment; Mental disorders; Monitor; Neuromodulator Receptors; Neurons; Norepinephrine; Play; Procedures; Process; Rattus; Role; Schizophrenia; Shock; Stimulus; Synaptic plasticity; System; Testing; Time; Training; United States; United States National Institutes of Health; aversive conditioning; comorbidity; conditioned fear; emotional experience; experience; experimental study; follow-up; in vivo; locus ceruleus structure; long term memory; member; memory consolidation; memory process; neural; neuromechanism; neuroregulation; novel; optogenetics; prevent; psychologic; rehearsal; response; sensor; tool

Abstract Novelty and surprise have long been known to facilitate learning and memory. At a functional level this makes sense; unexpected events have to be learned about so they can be predicted and responded to appropriately in the future. At a psychological level, surprising events have been shown to enhance memory because they induce rehearsal. Subjects tend to “think about” unexpected events more than familiar ones after they occur. This has been observed directly in humans (explicit rehearsal) and indirectly in animals (implicit rehearsal). In both cases, the memory enhancement can be eliminated by disrupting rehearsal with a distractor stimulus that is presented immediately after the novel event. Presenting the same distractor stimulus several minutes later has no effect. This suggests rehearsal is short-lasting and distinct from the process of memory consolidation, which stabilizes new information for several hours after learning. In addition to increasing rehearsal, novel events also trigger the release of norepinephrine (NE) and dopamine (DA), which are known to enhance synaptic plasticity. Blocking receptors for these neuromodulators in the hippocampus prevents animals from forming new spatial and contextual memories. Based on these findings, we hypothesize that surprising events enhance memory because they induce catecholamine release at the same time the hippocampus is actively rehearsing/replaying new information. Our preliminary data demonstrate that NE and DA are both released in the hippocampus during and after the presentation of an unexpected aversive stimulus. At the same time, there is an increase in sharp-wave ripple oscillations (SWRs), which are known to contain replay sequences for recently encountered stimuli. Consequently, we will test the hypothesis above by monitoring and manipulating catecholamine release in real-time during an aversive learning task while simultaneously recording oscillations and single unit activity in the hippocampus.

摘要 新奇和惊奇早就被认为有助于学习和记忆。在功能层面上，这是有意义的; 必须了解意外事件，以便将来能够预测和适当应对。在 在心理学水平上，令人惊讶的事件被证明可以增强记忆，因为它们会诱导复述。受试者倾向于 在意外事件发生后，比熟悉的事件更能“思考”意外事件。这在人类身上已经被直接观察到了 （外显复述）和间接（内隐复述）。在这两种情况下，记忆增强可以是 通过用在新事件之后立即呈现的干扰物刺激扰乱排练来消除。 几分钟后呈现相同的干扰刺激没有效果。这表明排练是短暂的， 与记忆巩固过程不同，记忆巩固过程在学习后几个小时内稳定新信息。在 除了增加排练，新事件也会触发去甲肾上腺素（NE）和多巴胺（DA）的释放， 可以增强突触的可塑性阻断海马体中这些神经调质的受体， 动物形成新的空间和背景记忆。基于这些发现，我们假设令人惊讶的是， 事件增强记忆，因为它们在海马体活跃的同时诱导儿茶酚胺释放。 排练/重放新信息。我们的初步数据表明，NE和DA都是在 海马体在一个意想不到的令人厌恶的刺激呈现期间和之后。与此同时， 在尖锐波涟漪振荡（SWR）中，已知其包含最近遇到的刺激的重放序列。 因此，我们将通过实时监测和操纵儿茶酚胺的释放来测试上述假设 同时记录海马体中的振荡和单个单元活动。