Trace and contextual fear conditioning require neural activity and NMDA receptor-dependent transmission in the medial prefrontal cortex
Trace and contextual fear conditioning require neural activity and NMDA receptor-dependent transmission in the medial prefrontal cortex
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DOI：
10.1101/lm.1597410
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发表时间：
2010-06-01
影响因子：
2
通讯作者：
Helmstetter, Fred J.
中科院分区：
文献类型：
--
作者：
Gilmartin, Marieke R.;Helmstetter, Fred J.
内侧前额叶皮层（mPFC）对记忆形成的贡献是最近相当感兴趣的一个主题。值得注意的是，在这种结构中支持记忆获取的机制知之甚少。mPFC参与了微量恐惧条件反射的获得，这是一项需要将条件刺激（CS）和厌恶性无条件刺激（UCS）跨时间间隔联系起来的任务。在大鼠和人类受试者中，额叶区域在分离CS和UCS的跟踪间隔期间显示出增加的活动。我们研究了大鼠前额叶神经活动对微量恐惧条件反射获得的贡献，微量注入γ-氨基丁酸A型（GABA（A））受体激动剂蝇蕈醇。我们还研究了前额叶N-甲基-D-天冬氨酸（NMDA）受体介导的信号在使用NMDA受体拮抗剂2-氨基-5-膦酰基戊酸（APV）的微量恐惧条件反射的作用。暂时失活的前额叶活动蝇蕈醇或阻断NMDA受体依赖的传输mPFC损害收购的痕迹，但不延迟，条件性恐惧反应。同时获得的背景恐惧反应也受损的药物治疗大鼠暴露于微量或延迟，但不成对的，培训方案。我们的研究结果支持的想法，突触可塑性内的mPFC是至关重要的记忆的长期存储在跟踪恐惧条件反射。
The contribution of the medial prefrontal cortex (mPFC) to the formation of memory is a subject of considerable recent interest. Notably, the mechanisms supporting memory acquisition in this structure are poorly understood. The mPFC has been implicated in the acquisition of trace fear conditioning, a task that requires the association of a conditional stimulus (CS) and an aversive unconditional stimulus (UCS) across a temporal gap. In both rat and human subjects, frontal regions show increased activity during the trace interval separating the CS and UCS. We investigated the contribution of prefrontal neural activity in the rat to the acquisition of trace fear conditioning using microinfusions of the gamma-aminobutyric acid type A (GABA(A)) receptor agonist muscimol. We also investigated the role of prefrontal N-methyl-D-aspartate (NMDA) receptor-mediated signaling in trace fear conditioning using the NMDA receptor antagonist 2-amino-5-phosphonovaleric acid (APV). Temporary inactivation of prefrontal activity with muscimol or blockade of NMDA receptor-dependent transmission in mPFC impaired the acquisition of trace, but not delay, conditional fear responses. Simultaneously acquired contextual fear responses were also impaired in drug-treated rats exposed to trace or delay, but not unpaired, training protocols. Our results support the idea that synaptic plasticity within the mPFC is critical for the long-term storage of memory in trace fear conditioning.