Persistent, generalized hypersensitivity of olfactory bulb interneurons after olfactory fear generalization
Persistent, generalized hypersensitivity of olfactory bulb interneurons after olfactory fear generalization
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DOI：
10.1016/j.nlm.2017.11.004
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发表时间：
2017-12-01
影响因子：
2.7
通讯作者：
McGann, John P.
中科院分区：
文献类型：
--
作者：
Kass, Marley D.;McGann, John P.
将恐惧从先前的威胁性刺激泛化到新的但相关的刺激可能是有益的，但如果恐惧过度泛化到不适当的情况，它可能会产生适应不良的行为，并导致病理性焦虑。适当的恐惧学习可以选择性地促进威胁预测刺激的早期感觉处理，但目前尚不清楚恐惧泛化是否具有类似的泛化神经感觉后果。我们在体内进行光学神经生理学观察嗅球周围中间神经元群体的气味诱发的神经活动1天前，1天后，和1个月后，每只小鼠进行了嗅觉恐惧条件反射范式，旨在促进广泛的恐惧气味。行为和神经生理学的变化进行了评估，以响应一组不同的相似性的威胁预测气味在每个时间点的气味。条件反射后，所有的气味引起类似水平的冻结行为，无论相似的威胁预测气味。冷冻显着相关的气味诱发的肾小球周围细胞活性的变化，包括一个强大的，广义的促进所有气味的反应，扩大气味调谐，并增加神经反应较低的气味浓度。这些普遍的影响发生在24小时内的一个单一的条件反射会议，持续至少1个月，甚至在大脑的反应气味的第一时间检测。广泛性恐惧不仅包括威胁预测刺激的早期感觉加工改变，而且包括新颖但分类相似的刺激，这一发现可能对伴有感觉后遗症的焦虑症的病因学和治疗具有重要意义。
Generalization of fear from previously threatening stimuli to novel but related stimuli can be beneficial, but if fear overgeneralizes to inappropriate situations it can produce maladaptive behaviors and contribute to pathological anxiety. Appropriate fear learning can selectively facilitate early sensory processing of threat-predictive stimuli, but it is unknown if fear generalization has similarly generalized neurosensory consequences. We performed in vivo optical neurophysiology to visualize odor-evoked neural activity in populations of periglomerular interneurons in the olfactory bulb 1 day before, 1 day after, and 1 month after each mouse underwent an olfactory fear conditioning paradigm designed to promote generalized fear of odors. Behavioral and neurophysiological changes were assessed in response to a panel of odors that varied in similarity to the threat predictive odor at each time point. After conditioning, all odors evoked similar levels of freezing behavior, regardless of similarity to the threat-predictive odor. Freezing significantly correlated with large changes in odor-evoked periglomerular cell activity, including a robust, generalized facilitation of the response to all odors, broadened odor tuning, and increased neural responses to lower odor concentrations. These generalized effects occurred within 24 h of a single conditioning session, persisted for at least 1 month, and were detectable even in the first moments of the brain's response to odors. The finding that generalized fear includes altered early sensory processing of not only the threat-predictive stimulus but also novel though categorically-similar stimuli may have important implications for the etiology and treatment of anxiety disorders with sensory sequelae.