Memory generalization after one-trial contextual fear conditioning: Effects of sex and neuropeptide S receptor deficiency
Memory generalization after one-trial contextual fear conditioning: Effects of sex and neuropeptide S receptor deficiency
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DOI：
10.1016/j.bbr.2018.12.046
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发表时间：
2019-04-01
影响因子：
2.7
通讯作者：
Fendt, Markus
中科院分区：
文献类型：
--
作者：
Germer, Josephine;Kahl, Evelyn;Fendt, Markus
在实验室小鼠中进行的一次试验情境恐惧条件反射会产生一种恐惧记忆，这种恐惧记忆在条件反射后不久就相对于原始条件反射情境相对特定，但在一个月的潜伏期后变得更加不特定。这个过程称为恐惧记忆的泛化，用于研究可能涉及创伤后应激障碍发病机制的过程。在本研究中，我们研究了性别和神经肽 S 受体 (NPSR) 缺乏在一项试验情境恐惧调节中的影响。除了背景恐惧之外，我们还测量了小鼠的惊吓反应、焦虑和皮质酮血浆水平。我们的数据显示了性别和 NPSR 缺乏对冻结行为、惊吓程度和焦虑水平的主要影响。然而，潜伏期后情境恐惧记忆的泛化不受性别影响。值得注意的是，NPSR 缺陷小鼠在条件反射后不久比其野生型同窝小鼠具有更具体的恐惧记忆，但在孵化时间后，所有基因型都具有普遍的恐惧记忆。目前的数据进一步表明，血浆皮质酮水平在孵育时间后增加。这种增加在 NPSR 缺陷小鼠中更为明显。综上所述，我们的研究证实了一项试验情境恐惧条件反射适用于研究潜伏时间对恐惧记忆泛化的影响，但也表明需要不进行潜伏期的对照组。我们进一步证明，在 NPSR 缺陷小鼠中，孵育时间后血浆皮质酮水平的增加被夸大。后一个发现表明 NPS 系统在调节皮质酮释放中发挥着重要作用。
One-trial contextual fear conditioning in laboratory mice results in a fear memory which is relatively specific to the original conditioning context shortly after conditioning but becomes more unspecific after an incubation time of one month. This process is called generalization of fear memory and is used to investigate processes which might be involved in the pathogenesis of post-traumatic stress disorder. In the present study, we investigated the effects of sex and neuropeptide S receptor (NPSR) deficiency in one-trial contextual fear conditioning. In addition to contextual fear, we also measured startle reactivity, anxiety and corticosterone plasma levels of the mice. Our data show main effects of sex and NPSR-deficiency on freezing behavior, startle magnitude, and anxiety levels. However, generalization of contextual fear memory after incubation time was not affected by sex. Notably, NPSR-deficient mice had a more specific fear memory shortly after conditioning than their wildtype littermates but after incubation time, all genotypes had a generalized fear memory. The present data further show that plasma corticosterone levels are increased after incubation time. This increase was significantly more pronounced in NPSR-deficient mice. Taken together, our study confirms the suitability of one trial contextual fear conditioning to study the effects of incubation time on fear memory generalization but also indicates the need for control groups without incubation. We further demonstrate that the increase of plasma corticosterone levels after incubation time is exaggerated in NPSR-deficient mice. The latter finding suggests an important role of the NPS system in the regulation of corticosterone release.