Texas Biomedical Device Center, The University of Texas at Dallas, 800 West Campbell Road, Richardson, TX 75080, United States; School of Behavioral Brain Sciences, The University of Texas at Dallas, 800 West Campbell Road, Richardson, TX 75080, United States.
Texas Biomedical Device Center, The University of Texas at Dallas, 800 West Campbell Road, Richardson, TX 75080, United States; School of Behavioral Brain Sciences, The University of Texas at Dallas, 800 West Campbell Road, Richardson, TX 75080, United States; Erik Jonsson School of Engineering and Computer Science, The University of Texas at Dallas, 800 West Campbell Road, Richardson, TX 75080, United States.
Neurobiol Learn Mem. 2021 May;181:107425. doi: 10.1016/j.nlm.2021.107425. Epub 2021 Mar 23.
Traumatic experiences involve complex sensory information, and individuals with trauma-related psychological disorders, such as posttraumatic stress disorder (PTSD), can exhibit abnormal fear to numerous different stimuli that remind them of the trauma. Vagus nerve stimulation (VNS) enhances extinction of auditory fear conditioning in rat models for PTSD. We recently found that VNS-paired extinction can also promote extinction generalization across different auditory cues. Here we tested whether VNS can enhance extinction of olfactory fear and promote extinction generalization across auditory and olfactory sensory modalities. Male Sprague Dawley rats were implanted with a stimulating cuff on the cervical vagus nerve. Rats then received two days of fear conditioning where olfactory (amyl acetate odor) and auditory (9 kHz tones) stimuli were concomitantly paired with footshock. Twenty-four hours later, rats were given three days of sham or VNS-paired extinction (5 stimulations, 30-sec trains at 0.4 mA) overlapping with presentation of either the olfactory or the auditory stimulus. Two days later, rats were given an extinction retention test where avoidance of the olfactory stimulus or freezing to the auditory stimulus were measured. VNS-paired with exposure to the olfactory stimulus during extinction reduced avoidance of the odor in the retention test. VNS-paired with exposure to the auditory stimulus during extinction also decreased avoidance of the olfactory cue, and VNS paired with exposure to the olfactory stimulus during extinction reduced freezing when the auditory stimulus was presented in the retention test. These results indicate that VNS enhances extinction of olfactory fear and promotes extinction generalization across different sensory modalities. Extinction generalization induced by VNS may therefore improve outcomes of exposure-based therapies.
创伤性经历涉及复杂的感觉信息，而与创伤相关的心理障碍（如创伤后应激障碍，PTSD）患者对许多不同的刺激物会表现出异常的恐惧，这些刺激物会让他们想起创伤。迷走神经刺激（VNS）增强了 PTSD 大鼠模型中听觉恐惧条件反射的消退。我们最近发现，VNS 配对的消退也可以促进不同听觉线索之间的消退泛化。在这里，我们测试了 VNS 是否可以增强嗅觉恐惧的消退，并促进听觉和嗅觉感觉模式之间的消退泛化。雄性 Sprague Dawley 大鼠在颈迷走神经上植入刺激袖带。然后，大鼠接受两天的恐惧条件反射训练，在此期间，嗅觉（乙酸戊酯气味）和听觉（9 kHz 音调）刺激与足底电击同时配对。24 小时后，大鼠接受 sham 或 VNS 配对的消退训练（5 次刺激，0.4 mA 强度 30 秒），与嗅觉或听觉刺激同时呈现。两天后，大鼠进行消退保持测试，测量其对嗅觉刺激的回避或对听觉刺激的冻结反应。在消退过程中，与嗅觉刺激配对的 VNS 暴露可减少保留测试中对气味的回避。在消退过程中，与听觉刺激配对的 VNS 暴露也减少了对嗅觉线索的回避，而在保留测试中呈现听觉刺激时，与嗅觉刺激配对的 VNS 暴露减少了冻结反应。这些结果表明，VNS 增强了嗅觉恐惧的消退，并促进了不同感觉模式之间的消退泛化。VNS 诱导的消退泛化可能会改善暴露疗法的效果。
