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.

抽象的 人们早就知道新奇和惊喜可以促进学习和记忆。从功能层面来说，这是有道理的； 必须了解意外事件，以便将来能够预测并做出适当反应。在一个 在心理层面上，令人惊讶的事件已被证明可以增强记忆，因为它们会引发预演。受试者倾向于 在意外事件发生后，比熟悉的事件更多地“思考”。这已在人类身上直接观察到 （显式排练）和间接在动物身上（内隐排练）。在这两种情况下，记忆增强都可以 通过在新事件发生后立即出现的干扰刺激来扰乱排练来消除这种情况。 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并且 与记忆巩固的过程不同，记忆巩固的过程是在学习后几个小时内稳定新信息。在 除了增加排练外，新事件还会引发去甲肾上腺素（NE）和多巴胺（DA）的释放，这 已知可以增强突触可塑性。阻断海马体中这些神经调节剂的受体可以防止 动物形成新的空间和情境记忆。基于这些发现，我们假设令人惊讶的 事件可以增强记忆力，因为它们会在海马体活跃的同时诱导儿茶酚胺释放 排练/重播新信息。我们的初步数据表明 NE 和 DA 均在 出现意外的厌恶刺激期间和之后的海马体。与此同时，还有增加 锐波纹波振荡 (SWR) 中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检验上述假设 在厌恶性学习任务期间，同时记录海马体的振荡和单个单元的活动。