Effects of extinction on cellular activity in the dorsal and ventral hippocampus

消退对背侧和腹侧海马细胞活动的影响

• 批准号: 9011380
• 负责人: Robin Yuan
• 金额: $ 4.36万
• 依托单位: UNIVERSITY OF PENNSYLVANIA
• 依托单位国家: 美国
• 财政年份: 2015
• 资助国家: 美国
• 起止时间: 2015-02-06 至 2017-02-05
• 项目状态: 已结题
• 来源: https://reporter.nih.gov/project-details/9011380
• 关键词: Affect; Amygdaloid structure; Animals; Area; Behavior; Brain region; Cells; Characteristics; Code; Communication; Data; Dorsal; Electrodes; Electrophysiology (science); Emotional; Emotions; Environment; Event; Extinction (Psychology); Failure; Fright; Health; Hippocampus (Brain); Implant; Individual; Lead; Learning; Location; Measures; Medial; Memory; Mus; Neurons; Patients; Pattern; Phase; Play; Population; Post-Traumatic Stress Disorders; Prefrontal Cortex; Process; Psychopathology; Pyramidal Cells; Retrieval; Role; Specific Phobia; Staging; Stimulus; awake; base; conditioned fear; conditioning; effective therapy; in vivo; insight; learning extinction; reconstruction; relating to nervous system; response; targeted treatment; traditional therapy

 DESCRIPTION (provided by applicant): Emotion has a powerful impact on memory, with fearful memories in particular maintaining a strong foothold long after the actual event. However, because continued fearful responding in the absence of danger can be detrimental, the ability to extinguish fearful memories is extremely important. During extinction, the fear response is reduced through repeated exposures without consequences to a stimulus previously associated with a fearful event. Many psychopathologies such as post-traumatic stress disorder and specific phobias are characterized by failures of extinction, resulting in persistent fearful responding. Extinction is widely believed to be a form of new learning rather than memory erasure, and it is context-specific; indeed, one limitation of traditional exposure therapies is the difficulty patients have in generalizing their new learning outside of the therapy context. The hippocampus is well-established as a region critical for contextual learning, and it may provide context-dependent gating of fear and extinction through its projections to the prelimbic and infralimbic regions of the medial prefrontal cortex, respectively. The objective of this application is to investigate how cellular firing patterns change during fear conditioning and extinction by analyzing the individual and population activity of place cells in the dorsal (Specifc Aim 1) and ventral (Specific Aim 2) hippocampus. Additionally, I will investigate how changes in hippocampal firing patterns affect phase locking and neuronal coherence along the hippocampal longitudinal axis and between the hippocampus and the mPFC (Specific Aim 3). Data for these Aims will be collected using in vivo single-unit and local field potential (LFP) recordings in awake, behaving C57bl/6 mice undergoing a fear conditioning and extinction paradigm. I hypothesize that both dorsal and ventral place cells will show changes in firing patterns after fear conditioning and extinction, suggesting that distinct representations are formed in the hippocampus to encode specific contexts for fearful and safe situations. Moreover, I predict that these changes will lead to increased coherence between the hippocampus and the prelimbic region during retrieval of the fearful representation, and increased coherence between the hippocampus and the infralimbic region during retrieval of the safe representation. In this way, the changes in firing pattern seen in the hippocampus can modulate communication between the hippocampus and other brain regions in order to provide contextual gating of behavior during fear and extinction. Understanding the neural substrates underlying these forms of learning may provide insights for creating more effective and targeted therapies.

 描述（由申请人提供）：情绪对记忆有强大的影响，特别是恐惧的记忆在实际事件发生后很长一段时间内仍然保持着强大的立足点。然而，因为在没有危险的情况下持续的恐惧反应可能是有害的，所以消除恐惧记忆的能力是非常重要的。在灭绝期间，恐惧反应会通过重复暴露于之前与恐惧事件相关的刺激而减少，而不会产生任何后果。许多精神病理学，如创伤后应激障碍和特定恐惧症的特点是灭绝失败，导致持续的恐惧反应。灭绝被广泛认为是一种新的学习形式，而不是记忆擦除，它是特定于环境的;事实上，传统暴露疗法的一个局限性是患者难以概括治疗之外的新学习 上下文海马体是公认的情境学习的关键区域，它可以通过其投射到内侧前额叶皮层的边缘前区和边缘下区，分别提供恐惧和灭绝的情境依赖门控。本申请的目的是研究在恐惧条件反射过程中细胞放电模式如何变化， 通过分析背侧（Specific Aim 1）和腹侧（Specific Aim 2）海马中位置细胞的个体和群体活性来观察灭绝。此外，我将研究海马放电模式的变化如何影响相位锁定和神经元的一致性沿着海马纵轴和海马和mPFC之间（具体目标3）。将在经历恐惧条件反射和消退范例的清醒、行为良好的C57 bl/6小鼠中使用体内单单位和局部场电位（LFP）记录来收集这些目标的数据。我假设，背侧和腹侧的位置细胞将显示在恐惧条件反射和灭绝后的放电模式的变化，这表明在海马体中形成了不同的表征，以编码恐惧和安全的情况下的特定上下文。此外，我预测，这些变化将导致增加海马和边缘前区之间的连贯性在检索的恐惧表示，并增加海马和边缘下区之间的连贯性在检索的安全表示。通过这种方式，在海马体中看到的放电模式的变化可以调节海马体和其他大脑区域之间的通信，以便在恐惧和灭绝期间提供行为的上下文门控。了解这些学习形式背后的神经基质可能会为创造更有效和更有针对性的疗法提供见解。

项目成果

HDAC I inhibition in the dorsal and ventral hippocampus differentially modulates predator-odor fear learning and generalization.

• DOI: 10.3389/fnins.2015.00319
• 发表时间: 2015
• 期刊: Frontiers in neuroscience
• 影响因子: 4.3
• 作者: Yuan RK;Hebert JC;Thomas AS;Wann EG;Muzzio IA
• 通讯作者: Muzzio IA

Extinction of Learned Fear Induces Hippocampal Place Cell Remapping.

习得性恐惧的消失会导致海马位置细胞重新映射。

• DOI: 10.1523/jneurosci.4477-14.2015
• 发表时间: 2015
• 期刊: The Journal of neuroscience : the official journal of the Society for Neuroscience
• 作者: Wang,MelissaE;Yuan,RobinK;Keinath,AlexanderT;RamosÁlvarez,ManuelM;Muzzio,IsabelA
• 通讯作者: Muzzio,IsabelA