Chemogenetic manipulation of the bed nucleus of the stria terminalis counteracts social behavioral deficits induced by early life stress in C57BL/6J mice
Chemogenetic manipulation of the bed nucleus of the stria terminalis counteracts social behavioral deficits induced by early life stress in C57BL/6J mice
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DOI：
10.1002/jnr.24644
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发表时间：
2020-06-01
影响因子：
4.2
通讯作者：
Halladay, Lindsay R.
中科院分区：
文献类型：
--
作者：
Emmons, Randi;Sadok, Tasneem;Halladay, Lindsay R.
在发育的关键时期遭受创伤会产生长期的不良影响。为了研究早期生活应激（ELS）引起的神经畸变，许多研究利用啮齿动物母体分离，即幼鼠间歇性地被剥夺正常发育所需的母体护理。这可能会产生与焦虑，奖励和社会行为有关的成年行为缺陷。终纹床核（BNST）编码焦虑样和社会行为的各个方面，并且在出生后早期也经历发育成熟，使其容易受到ELS的影响。小鼠进行母体分离（在出生后第2-5天（PD）分离4小时/天，在PD 6 -16分离8小时/天），在PD 17早期断奶，这导致了成年人在两部分社会互动任务中的行为缺陷，该任务旨在测试社会动机（在同性小说同类或空杯子之间选择）和社会新奇偏好（在原始新颖同种与新新颖同种之间的选择）。我们使用化学遗传学来非选择性地沉默或激活BNST中的神经元，以研究其在有或没有ELS病史的小鼠中在社会动机和社会新奇偏好中的作用。操纵BNST产生不同的社会行为的影响，在非应激与ELS小鼠;社会动机在非应激小鼠BNST激活后下降，但不变的BNST沉默，而ELS小鼠表现出没有变化的社会行为后，BNST激活，但表现出增强的社会动机，他们是缺乏事先BNST沉默。研究结果强调，BNST作为一个潜在的治疗目标，社会焦虑症挑起的童年创伤。
Trauma during critical periods of development can induce long-lasting adverse effects. To study neural aberrations resulting from early life stress (ELS), many studies utilize rodent maternal separation, whereby pups are intermittently deprived of maternal care necessary for proper development. This can produce adulthood behavioral deficits related to anxiety, reward, and social behavior. The bed nucleus of the stria terminalis (BNST) encodes aspects of anxiety-like and social behaviors, and also undergoes developmental maturation during the early postnatal period, rendering it vulnerable to effects of ELS. Mice underwent maternal separation (separation 4 hr/day during postnatal day (PD)2-5 and 8 hr/day on PD6-16) with early weaning on PD17, which induced behavioral deficits in adulthood performance on two-part social interaction task designed to test social motivation (choice between a same-sex novel conspecific or an empty cup) and social novelty preference (choice between the original-novel conspecific vs. a new-novel conspecific). We used chemogenetics to non-selectively silence or activate neurons in the BNST to examine its role in social motivation and social novelty preference, in mice with or without the history of ELS. Manipulation of BNST produced differing social behavior effects in non-stressed versus ELS mice; social motivation was decreased in non-stressed mice following BNST activation, but unchanged following BNST silencing, while ELS mice showed no change in social behavior after BNST activation, but exhibited enhancement of social motivation-for which they were deficient prior-following BNST silencing. Findings emphasize the BNST as a potential therapeutic target for social anxiety disorders instigated by childhood trauma.