Sexual differentiation of contextual fear responses.
Sexual differentiation of contextual fear responses.
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DOI：
10.1101/lm.047159.117
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发表时间：
2018-05
期刊：
影响因子：
--
通讯作者：
Poulos AM
中科院分区：
文献类型：
--
作者：
Colon L;Odynocki N;Santarelli A;Poulos AM
发育和性别分化对哺乳动物的神经解剖学和行为有组织的影响。先前的研究表明，与恐惧驱动的防御行为相关的大脑区域经历了一个漫长的、性别依赖的发展过程。在成年动物之外，关于条件性恐惧的发育性差异的证据很少。在这里，我们研究了雄性和雌性Long-Evans大鼠的发育年龄和性别如何影响巴甫洛夫恐惧反应的长期保留和泛化。实验1和2描述了青春期前大鼠（P24和P33）、青春期周围大鼠（P37）和成年大鼠（P60和P90）在厌恶学习水平增加的情况下对线索和情境恐惧的长期检索。实验3和4在婴儿（P19, P21）、青春期前（P24）和成年（P60）大鼠的最小厌恶学习（1次试验）过程中考察了语境处理。本研究发现，雄性和雌性大鼠在情境介导冻结的表达上表现出不同的发展轨迹，雄性大鼠的情境恐惧表达倾向于在成年期增加，而雌性大鼠则表现出相反的模式，在成年期减少情境恐惧表达。相对于较短的保留时间（1天），较长的保留时间间隔（14天）产生了总体上较高的情境恐惧表达，这一观察结果与恐惧孵化一致。在整个发展过程中，雄性大鼠表现出越来越多的情境恐惧，而雌性大鼠则没有。总的来说，这些发现提供了一个初步的证明，背景恐惧条件的性别差异在青春期之前就出现了，并遵循着一个明显的发育轨迹，直到成年，这与焦虑、创伤和压力相关疾病的病因学和流行病学中的性别差异惊人地相似。
Development and sex differentiation impart an organizational influence on the neuroanatomy and behavior of mammalian species. Prior studies suggest that brain regions associated with fear motivated defensive behavior undergo a protracted and sex-dependent development. Outside of adult animals, evidence for developmental sex differences in conditioned fear is sparse. Here, we examined in male and female Long-Evans rats how developmental age and sex affect the long-term retention and generalization of Pavlovian fear responses. Experiments 1 and 2 describe under increasing levels of aversive learning (three and five trials) the long-term retrieval of cued and context fear in preadolescent (P24 and P33), periadolescent (P37), and adult (P60 and P90) rats. Experiments 3 and 4 examined contextual processing under minimal aversive learning (1 trial) procedures in infant (P19, P21), preadolescent (P24), and adult (P60) rats. Here, we found that male and female rats display a divergent developmental trajectory in the expression of context-mediated freezing, such that context fear expression in males tends to increase toward adulthood, while females displayed an opposite pattern of decreasing context fear expression toward adulthood. Longer (14 d) retention intervals produced an overall heightened context fear expression relative to shorter (1 d) retention intervals an observation consistent with fear incubation. Male, but not Female rats showed increasing generalization of context fear across development. Collectively, these findings provide an initial demonstration that sexual differentiation of contextual fear conditioning emerges prior to puberty and follows a distinct developmental trajectory toward adulthood that strikingly parallels sex differences in the etiology and epidemiology of anxiety and trauma- and stressor-related disorders.
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