Molecular and Sellular Mechanisms Underlying an Olfactory Memory in the Context of Pregnancy Block

雌性老鼠对与它们交配的雄性老鼠的尿液气味形成了长期的嗅觉记忆。这种嗅觉记忆对它们的繁殖成功至关重要。现在已经确定，这种记忆的形成依赖于副嗅球（AOB）内的神经机制。本研究的目的是通过注入不同的药物，探讨嗅觉记忆在脑皮层内的突触和分子机制。研究结果如下：(1)在未交配的情况下，阻断AOB中的GABA受体可以阻止雄性在随后的交配中阻止怀孕，这表明GABA能阻断确实产生了嗅觉记忆。(2)关键时期AOB蛋白激酶的抑制阻止记忆的形成，但6小时后没有。(3)在交配后期（交配后3-6h）， AOB蛋白合成受到抑制，而在关键时期的早期，AOB蛋白合成未受到抑制，从而阻碍了记忆的形成。这些结果进一步表明，雌鼠对配偶信息素的识别在二尖瓣细胞和AOB颗粒细胞之间树突突触的突触效能变化中起着至关重要的作用。本研究的另一个目的是探讨这种记忆的电生理相关性。采用一维电流源-密度（CSD）方法，分析了麻醉雌性小鼠经v型鼻器官刺激后AOB外丛状层（EPL）的突触传递。CSD分析显示EPL中有一个主要的下沉（向内膜电流）。EPL中的sink被非NMDA受体拮抗剂CNQX阻断，但不被NMDA受体拮抗剂D-AP-5阻断，提示非NMDA受体在二尖瓣到颗粒细胞树突突触中的介导作用。我们还证明，AOB的投射激活杏仁核的兴奋性氨基酸受体和内侧视前区的胆囊收缩素- b受体，从而引起结节基底多巴胺能神经元的兴奋。少

Female mice form a long-term olfactory memory to the urinary odors of the male that mates with them. This olfactory memory is essential to their reproductive success. It is now established that the formation of this memory is dependent on neural mechanisms within the accessory olfactory bulb (AOB). The purpose of this study is to examine the synaptic and molecular mechanisms within the AOB for the olfactory memory by infusing various drugs into the AOB. The results are summarized as follow : (1) Blockade of the GABA receptors in the AOB without mating prevents any male from blocking pregnancy following a subsequent mating, suggesting that the GABAergic blockade does create an olfactory memory. (2) Protein kinase inhibition in the AOB during the critical period, but not 6 hours later, prevents memory formation. (3) Protein synthesis inhibition in the AOB in the late phase (3-6hours after mating) but not early phase of the critical period prevents memory formation. These results suggest … More that changes in synaptic efficacy at the dendrodendritic synapse between mitral and granule cells in the AOB are crucial to recognition of the mate's pheromones by female mice.A further purpose of this study is to approach to electrophysiological correlates of this memory. Synaptic transmission in the External Plexiform Layer (EPL) of the AOB following stimulation of the vomeronasal organ was analyzed using a one-dimensional Current Source-Density (CSD) method in anaesthetized female mice. The CSD analysis revealed a major sink (inward membrane current) in the EPL. The sink in the EPL was blocked by the non-NMDA receptor antagonist, CNQX, but not by the NMDA receptor receptor antagonist, D-AP-5, suggesting the mediation of non-NMDA receptors in the mitral to granule cell dendrodendritic synapse.We also demonstrated that the projections of the AOB activate excitatory amino acid receptors in the amygdala and cholecystokinin-B receptors in the medial preoptic area, thereby causing excitation of tuberoinfundibular dopaminergic neurons. Less