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: 8908718
• 负责人: Robin Yuan
• 金额: $ 4.31万
• 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/8908718
• 关键词: Affect; Amygdaloid structure; Animals; Area; Behavior; Brain region; Cells; Characteristics; Code; Communication; Data; Dorsal; Electrodes; Emotional; Emotions; Environment; Event; Extinction (Psychology); Failure; Fright; 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; public health relevance; 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(申请人提供)：情绪对记忆有强大的影响，尤其是恐惧的记忆在实际事件发生后很长一段时间内保持着强大的立足点。然而，由于在没有危险的情况下持续的恐惧反应可能是有害的，消除恐惧记忆的能力是极其重要的。在物种灭绝期间，通过反复暴露于先前与恐惧事件相关的刺激而不会产生后果，恐惧反应会减少。许多精神病理疾病，如创伤后应激障碍和特定的恐惧症，都以灭绝失败为特征，导致持续的恐惧反应。消亡被广泛认为是一种新的学习形式，而不是记忆擦除，而且它是特定于背景的；事实上，传统暴露疗法的一个局限性是患者在治疗之外很难概括他们的新学习。 背景。海马体是一个对语境学习至关重要的区域，它可能通过分别投射到内侧前额叶皮质的前缘和下缘区域，提供与语境相关的恐惧和消退的门控。这个应用程序的目标是研究细胞放电模式在恐惧条件反射和 通过分析背侧(特定目标1)和腹侧(特定目标2)海马区定位细胞的个体和群体活动来进行灭绝。此外，我将研究海马区放电模式的变化如何影响沿海马体纵轴以及海马区和mPFC之间的相位锁定和神经元一致性(特定目标3)。这些目标的数据将使用清醒的C57BL/6小鼠的活体单单位和局部场电位(LFP)记录来收集，这些小鼠正在经历恐惧条件反射和消退范式。我假设，背侧和腹侧位置细胞在恐惧条件反射和消退后都会显示出放电模式的变化，这表明在海马体中形成了不同的表征，以编码恐惧和安全情况下的特定背景。此外，我预测，在提取恐惧表征时，这些变化将导致海马区和前脑区域之间的连贯性增强，而在提取安全表征时，这些变化将导致海马区和下缘区之间的连贯性增强。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，以便在恐惧和消退期间提供背景门控行为。了解这些学习形式背后的神经基础可能会为创造更有效和更有针对性的治疗方法提供见解。