Department of Biology, Boston University, Boston, MA, 02215, USA.
Department of Psychological and Brain Sciences, Boston University, Boston, MA, USA.
Eur J Neurosci. 2017 Aug;46(4):2035-2046. doi: 10.1111/ejn.13636. Epub 2017 Aug 1.
Sexually naïve estrous female mice seek out male urinary pheromones; however, they initially display little receptive (lordosis) behavior in response to male mounts. Vomeronasal-accessory olfactory bulb inputs to the medial amygdala (Me) regulate courtship in female rodents. We used a reversible inhibitory chemogenetic technique (Designer Receptors Exclusively Activated by Designer Drugs; DREADDs) to assess the contribution of Me signaling to females' preference for male pheromones and improvement in receptivity normally seen with repeated testing. Sexually naïve females received bilateral Me injections of an adeno-associated virus carrying an inhibitory DREADD. Females were later ovariectomized, treated with ovarian hormones, and given behavioral tests following intraperitoneal injections of saline or clozapine-N-oxide (CNO; which hyperpolarizes infected Me neurons). CNO attenuated females' preference to investigate male vs. female urinary odors. Repeated CNO treatment also slowed the increase in lordosis otherwise seen in females given saline. However, when saline was given to females previously treated with CNO, their lordosis quotients were as high as other females repeatedly given saline. No disruptive behavioral effects of CNO were seen in estrous females lacking DREADD infections of the Me. Finally, CNO attenuated the ability of male pheromones to stimulate Fos expression in the Me of DREADD-infected mice but not in non-infected females. Our results affirm the importance of Me signaling in females' chemosensory preferences and in the acute expression of lordosis. However, they provide no indication that Me signaling is required for the increase in receptivity normally seen after repeated hormone priming and testing with a male.
性不成熟的发情雌性小鼠会寻找雄性尿液信息素；然而，它们最初对雄性的交配行为表现出很少的接受（背弓）行为。犁鼻器辅助嗅觉球到杏仁内侧核（Me）的输入调节雌性啮齿动物的求偶行为。我们使用了一种可逆的抑制性化学遗传技术（Designer Receptors Exclusively Activated by Designer Drugs；DREADDs）来评估 Me 信号对雌性对雄性信息素的偏好以及对通过重复测试通常看到的接受性提高的贡献。性不成熟的雌性接受双侧 Me 注射携带抑制性 DREADD 的腺相关病毒。随后，雌性被卵巢切除术，用卵巢激素处理，并在腹腔内注射盐水或氯氮平-N-氧化物（CNO；使感染的 Me 神经元去极化）后进行行为测试。CNO 减弱了雌性对雄性尿液气味与雌性尿液气味的偏好。重复的 CNO 处理也减缓了在给予盐水的雌性中通常看到的背弓增加。然而，当 CNO 给予以前用 CNO 处理过的雌性时，它们的背弓比率与其他反复给予盐水的雌性一样高。在没有 Me 感染的 DREADD 的发情雌性中，CNO 没有观察到行为破坏作用。最后，CNO 减弱了雄性信息素刺激 DREADD 感染的小鼠 Me 中 Fos 表达的能力，但对非感染的雌性没有影响。我们的结果证实了 Me 信号在雌性化学感觉偏好和背弓的急性表达中的重要性。然而，它们并没有表明 Me 信号是在反复激素启动和与雄性交配测试后通常看到的接受性增加所必需的。
