Low-Frequency Stimulation Depresses the Primate Anterior-Cingulate-Cortex and Prevents Spontaneous Recovery of Aversive Memories
Low-Frequency Stimulation Depresses the Primate Anterior-Cingulate-Cortex and Prevents Spontaneous Recovery of Aversive Memories
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DOI：
10.1523/jneurosci.6481-11.2012
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发表时间：
2012-06-20
影响因子：
5.3
通讯作者：
Paz, Rony
中科院分区：
文献类型：
--
作者：
Klavir, Oded;Genud-Gabai, Rotem;Paz, Rony
背前扣带皮层（dACC）的功能异常是焦虑症，特别是创伤后应激障碍（PTSD）的基础。有前途的和常见的行为方法的有效性有限，许多受试者表现出自发的恐惧恢复，在灭绝训练后的动物模型中也很明显。在这里，我们使用低频刺激（LFS），一种诱导长期抑郁的协议，目的是影响由恐惧获得和消退引起的突触可塑性。我们使用厌恶条件反射的音调或视觉刺激配对的厌恶空气喷到眼睛中的痕迹条件反射范例。我们发现，LFS在非人灵长类动物（食蟹猴）的dACC，当结合灭绝训练，是成功地防止自发恢复的记忆24-72小时后灭绝。我们同时记录单个单位和局部场电位的dACC，并表明LFS逐渐压抑诱发反应。此外，这种神经兴奋性的降低预示着夜间自发恢复的成功减少。最后，我们表明，当使用视觉或听觉通道作为条件刺激时，就会出现这种效应，并且这种减少是条件通道所特有的。我们的研究结果表明，灵长类动物的dACC积极参与维持原始的厌恶记忆，并提出LFS与行为治疗相结合，可能会显着改善严重病例的治疗。
Functional abnormalities in the dorsal-anterior-cingulate-cortex (dACC) underlie anxiety disorders and specifically post-traumatic stress disorder (PTSD). Promising and common behavioral approaches have limited effectiveness and many subjects exhibit spontaneous recovery of fear, as also evident in animal models following extinction training. Here, we use low-frequency stimulation (LFS), a protocol shown to induce long-term depression, with the aim of affecting synaptic plasticity induced by fear acquisition and extinction. We use aversive conditioning of either tone or visual stimuli paired with an aversive air-puff to the eye in a trace-conditioning paradigm. We find that LFS in the nonhuman primate (Macaca fascicularis) dACC, when combined with extinction training, was successful in preventing spontaneous recovery of the memory 24-72 h following extinction. We simultaneously record single-units and local-field-potentials across the dACC, and show that LFS gradually depressed evoked responses. Moreover, this decrease in neural excitability predicted the successful reduction of overnight spontaneous recovery on a day-by-day basis. Finally, we show that this effect occurs when using either visual or auditory modality as the conditioned stimulus, and that the reduction was specific to the conditioned modality. Our results suggest that the primate dACC is actively involved in maintaining the original aversive memory, and propose that a combination of LFS with behavioral therapy might significantly improve treatment in severe cases.