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，尤其是恐惧记忆在实际事件发生后很长一段时间内仍能保持牢固的立足点。然而，由于在没有危险的情况下持续的恐惧反应可能是艰苦的，因此消除恐惧的能力。在消退过程中，恐惧反应会通过重复暴露而减少，而不会对先前与恐惧事件相关的刺激产生任何后果，例如创伤后应激障碍和特定恐惧症的特征是消退失败。导致持续的恐惧反应被广泛认为是一种新的学习形式，而不是记忆擦除，而且它是针对具体情况的，传统暴露疗法的一个局限性是患者很难将他们的新学习概括出来。治疗 海马体被认为是情境学习的关键区域，它可以通过其分别投射到内侧前额叶皮层的前边缘和下边缘区域来提供依赖于情境的恐惧和消退门控。是为了研究在恐惧调节过程中细胞放电模式如何变化 通过分析背侧（特定目标 1）和腹侧（特定目标 2）海马中位置细胞的个体和群体活动，我将研究海马放电模式的变化如何影响沿海马纵轴的锁相和神经一致性。以及海马体和 mPFC 之间（具体目标 3）将使用体内单单位和局部场电位 (LFP) 收集这些目标的数据。通过对清醒、行为 C57bl/6 小鼠进行恐惧条件反射和消退范式的记录，我发现背侧和腹侧位置细胞在恐惧条件反射和消退后都会表现出放电模式的变化，这表明海马体中形成了不同的表征来编码特定的信号。此外，我预测这些变化将导致在恢复恐惧表征期间海马体和前边缘区域之间的一致性增加，以及恐惧表征之间的一致性增加。通过这种方式，海马体中观察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行为的上下文门控。这些学习形式背后的神经基质可能为创造更有效和更有针对性的治疗提供见解。

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