Conditioned odor aversion induces social anxiety towards females in wild-type and TrpC2 knockout male mice
Conditioned odor aversion induces social anxiety towards females in wild-type and TrpC2 knockout male mice
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DOI：
10.1111/gbb.12320
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发表时间：
2016-11-01
影响因子：
2.5
通讯作者：
Kimchi, T.
中科院分区：
文献类型：
--
作者：
Beny, Y.;Kimchi, T.
雌性发出的信息素输入对同种雄性具有内在的奖励价值，促进了潜在交配对象的接近和研究。在小鼠中，这些输入主要由犁鼻器（VNO）和主嗅上皮（MOE）检测。我们研究了vno介导的输入在生殖反应的经验依赖可塑性中的作用。我们在成年、野生型（WT）雄性小鼠和vno介导的信号转导（TrpC2(-/-)）受损的雄性小鼠上应用了性别特异性条件气味厌恶（COA）范式。我们发现，对女性弄脏的被褥进行COA处理的WT雄性失去了对女性气味的先天偏好，并表现出较低的接近性接受雌性的动机。COA还消除了通常在接触女性气味后出现的睾丸激素激增。此外，受条件限制的雄性在交配行为上表现出损害，这种损害持续了数周。令人惊讶的是，这些雄性也对接受交配的雌性表现出恐惧行为，包括冻结和逃跑反应。相比之下，对雄性信息素进行COA处理的WT雄性嗅觉偏好没有变化，而雄性间攻击行为仅略微显著升高。最后，我们发现TrpC2（-/-）雄性能够厌恶女性弄脏的床上用品，并在COA后对女性线索的反应中表现出类似的行为改变。我们的研究结果表明，雌性信息素的内在奖励价值可以通过联想嗅觉学习被覆盖，而联想嗅觉学习独立于VNO输入，可能是通过MOE信号。
Female-emitted pheromonal inputs possess an intrinsic rewarding value for conspecific males, promoting approach and investigation of the potential mating partner. In mice these inputs are detected mainly by the vomeronasal organ (VNO) and the main olfactory epithelium (MOE). We investigated the role of VNO-mediated inputs in experience-dependent plasticity of reproductive responses. We applied a sex-specific conditioned odor aversion (COA) paradigm on adult, wild-type (WT) male mice and on malemice impaired in VNO-mediated signal transduction (TrpC2(-/-)). We found that WT males, which underwent COA to female-soiled bedding, lost their innate preference to female odors and presented lower motivation to approach a sexually receptive female. COA also abolished the testosterone surge normally seen following exposure to female odors. Moreover, the conditioned males displayed impairments in copulatory behaviors, which lasted for several weeks. Surprisingly, these males also exhibited phobic behaviors towards receptive females, including freezing and fleeing responses. In contrast, WT males which underwent COA specifically to male pheromones showed no change in olfactory preference and only a marginally significant elevation in intermale aggression. Finally, we show that TrpC2(-/-) maleswere able to acquire aversion to female-soiled bedding and presented similar behavioral alterations following COA in their responses to female cues. Our results demonstrate that the intrinsic rewarding value of female pheromones can be overridden through associative olfactory learning, which occurs independently of VNO inputs, probably through MOE signaling.