Genetic dissection of pheromone processing reveals main olfactory system-mediated social behaviors in mice
Genetic dissection of pheromone processing reveals main olfactory system-mediated social behaviors in mice
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DOI：
10.1073/pnas.1416723112
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发表时间：
2015-01-20
影响因子：
11.1
通讯作者：
Kobayakawa, Ko
中科院分区：
文献类型：
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作者：
Matsuo, Tomohiko;Hattori, Tatsuya;Kobayakawa, Ko
大多数哺乳动物有两个主要的嗅觉子系统：主嗅觉系统（MOS）和犁鼻系统（VNS）。现在人们普遍认为，控制社会行为的信息素范围是由 VNS 和 MOS 共同处理的。然而，每个子系统在社会行为中的功能贡献仍不清楚。为了从基因上分离 MOS 和 VNS 功能，我们建立了两个条件敲除小鼠品系，导致整个 MOS 或背侧 MOS 功能丧失。全MOS功能丧失的小鼠在主动嗅觉方面表现出严重缺陷，并且在整个新生儿期存活率较差。相反，当功能丧失仅限于背侧 MOB 时，嗅探行为、信息素识别和 VNS 活动得以维持。然而，我们观察到了广泛的社会行为缺陷：对女性尿液的吸引力和随之而来的超声波发声、化学研究偏好、攻击性、母性行为以及对警报信息素做出反应的风险评估行为。信息素检测和信息素行为诱导的功能分离表明，前嗅核（AON）调节着 MOS 下游的社会行为。病变分析和神经激活图谱显示，多个杏仁核和下丘脑核（表达社会行为的重要区域）中的信息素激活依赖于 MOS 和 AON 功能。 MOS-AON 介导的信息素途径的鉴定可能有助于了解不具有功能性 VNS 的动物（包括人类）的信息素信号传导。
Most mammals have two major olfactory subsystems: the main olfactory system (MOS) and vomeronasal system (VNS). It is now widely accepted that the range of pheromones that control social behaviors are processed by both the VNS and the MOS. However, the functional contributions of each subsystem in social behavior remain unclear. To genetically dissociate the MOS and VNS functions, we established two conditional knockout mouse lines that led to either loss-of-function in the entire MOS or in the dorsal MOS. Mice with whole-MOS loss-of-function displayed severe defects in active sniffing and poor survival through the neonatal period. In contrast, when loss-of-function was confined to the dorsal MOB, sniffing behavior, pheromone recognition, and VNS activity were maintained. However, defects in a wide spectrum of social behaviors were observed: attraction to female urine and the accompanying ultrasonic vocalizations, chemoinvestigatory preference, aggression, maternal behaviors, and risk-assessment behaviors in response to an alarm pheromone. Functional dissociation of pheromone detection and pheromonal induction of behaviors showed the anterior olfactory nucleus (AON)-regulated social behaviors downstream from the MOS. Lesion analysis and neural activation mapping showed pheromonal activation in multiple amygdaloid and hypothalamic nuclei, important regions for the expression of social behavior, was dependent on MOS and AON functions. Identification of the MOS-AON-mediated pheromone pathway may provide insights into pheromone signaling in animals that do not possess a functional VNS, including humans.