Postweaning Isolation Alters the Responses of Auditory Neurons to Serotonergic Modulation
Postweaning Isolation Alters the Responses of Auditory Neurons to Serotonergic Modulation
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DOI：
10.1093/icb/icab051
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发表时间：
2021-05-11
影响因子：
2.6
通讯作者：
Hurley, Laura M.
中科院分区：
文献类型：
--
作者：
Davis, Sarah E. D.;Sansone, Jack M.;Hurley, Laura M.
青少年的社会经历，例如社会孤立，对交流行为（包括信号的产生和接收）有着深远的影响。在当前的研究中，我们探索了对神经调节剂血清素的反应作为早期生活社会隔离和听觉处理之间潜在的机制联系。血清素能系统对许多大脑区域的社会隔离很敏感，包括下丘（IC）（听觉中脑核）。我们通过测量雌性小鼠 IC 中的 cFos（一种早期基因产物）来研究社会经历对血清素反应性的影响。通过给断奶后在社会经历中经历极端二分法的小鼠施用芬氟拉明、pCPA或盐水来从药理学上操纵血清素：被圈养在社会群体中还是单独饲养。这些小鼠接受了一段 60 分钟的异性互动发声录音并进行灌注。使用免疫组织化学，我们测量了 IC 主要分区中 cFos 阳性 (cFosthorn) 细胞核的密度。居住条件、药物治疗和IC分区均对cFostorn密度有显着影响。中央 IC 显示出最高密度的 cFosthorn 细胞，并且住房条件和药物治疗的影响也最明显。在中央 IC 中，芬氟拉明治疗后的 cFosthorn 密度高于生理盐水，而 pCPA 治疗后的 cFosthorn 密度低于芬氟拉明。在两个药物治疗组中，单独饲养的小鼠均表现出比社会饲养的小鼠更高的 cFosthorn 密度，但在盐水组中则不然。药物治疗而非饲养条件对梳理、挖掘、饲养和运动行为有强烈影响。一旦药物条件的影响得到控制，cFosthorn 密度和行为之间就不存在跨个体的相关性。这些发现表明听觉神经元对血清素神经调节的反应受到早期生活经历的影响。
Juvenile social experience, such as social isolation, has profound effects on communicative behavior, including signal production and reception. In the current study, we explored responsiveness to the neuromodulator serotonin as a potential mechanistic link between early life social isolation and auditory processing. The serotonergic system is sensitive to social isolation in many brain regions including the inferior colliculus (IC), an auditory midbrain nucleus. We investigated the effects of social experience on serotonergic responsiveness by measuring cFos, an immediate early gene product, in the IC of female mice. Serotonin was manipulated pharmacologically by administering fenfluramine, pCPA, or saline to mice that had undergone an extreme dichotomy in social experience after weaning: being housed in social groups versus individually. These mice were exposed to a 60-min recording of vocalizations from an opposite-sex interaction and perfused. Using immunohistochemistry, we measured the density of cFos-positive (cFosthorn) nuclei in the major subdivisions of the IC. Housing condition, drug treatment, and IC subregion all had a significant effect on cFosthorn density. The central IC showed the highest density of cFosthorn cells and also the most pronounced effects of housing condition and drug treatment. In the central IC, cFosthorn density was higher following fenfluramine treatment than saline, and lower following pCPA treatment than fenfluramine. Individually housed mice showed a higher cFosthorn density than socially housed mice in both of the pharmacological treatment groups, but not in the saline group. Drug treatment but not housing condition had strong effects on the behaviors of grooming, digging, rearing, and movement. Once the effects of drug condition were controlled, there were no across-individual correlations between cFosthorn densities and behaviors. These findings suggest that the responses of auditory neurons to neuromodulation by serotonin are influenced by early life experience.