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（由适用提供）：情感对记忆有强大的影响，尤其是在实际事件发生后很长时间保持强大的立足点。但是，由于在没有危险的情况下持续的恐惧反应可能是有害的，因此熄灭可怕记忆的能力极为重要。在延长期间，恐惧反应通过反复的暴露减少，而不会对以前与可怕事件相关的刺激产生影响。许多心理病理学，例如创伤后应激障碍和特定的恐惧症的特征是扩展失败，导致持续的可怕反应。人们普遍认为灭绝是一种新学习的一种形式，而不是记忆擦除，它是特定于上下文的。确实，传统暴露疗法的一个局限性是患者在疗法之外概括他们的新学习 语境。海马是对上下文学习至关重要的区域，它可以通过其项目通过其向内侧前额叶皮层的前临界和注册区域提供依赖上下文的恐惧和扩展门控。该应用的目的是研究恐惧调节期间细胞发射模式如何变化 通过分析背侧细胞的个体和种群活性（特定目标1）和腹侧（特定目标2）海马来消灭。此外，我将研究海马发射模式的变化如何影响沿海马纵向轴以及海马和MPFC之间的相位锁定和神经元相干性（特定的目标3）。这些目标的数据将使用醒着的体内单单元和局部田间电位（LFP）记录收集，表现出恐惧条件和扩展范式的C57BL/6小鼠。我假设背侧和腹侧位置细胞都会在恐惧调理和扩展后显示出射击模式的变化，这表明在海马中形成了不同的表示形式，以编码特定的上下文，以解决恐惧和安全的情况。此外，我预测这些变化将导致海马与可恐惧代表的检索期间海马与前区域之间的一致性增加，并在检索安全表示期间海马与灌木丛区域之间的相干性增加。这样，海马中看到的发射模式的变化可以调节海马和其他大脑区域之间的通信，以便在恐惧和扩展过程中提供行为的上下文门控。了解这些形式的学习形式的神经底物可以为创建更有效和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