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是必不可少的。现在已经证实，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向AOB内注入不同的药物来研究AOB内影响嗅觉记忆的突触和分子机制。结果如下：(1)阻断AOB中的GABA受体，在没有交配的情况下，阻止任何雄性在随后的交配后阻止怀孕，这表明GABA能阻断确实创造了嗅觉记忆。(2)在关键时期，但不是在6小时后，抑制AOB中的蛋白激酶可以阻止记忆的形成。(3)在关键期的晚期(交配后3-6小时)而不是在关键期的早期阶段，AOB的蛋白质合成抑制阻止了记忆的形成。这些结果表明…此外，AOB中二尖瓣和颗粒细胞之间树突突触的突触效能的变化对于雌性小鼠识别交配信息素是至关重要的。本研究的进一步目的是探讨这种记忆的电生理关联。用一维电流源密度法(CSD)分析了刺激犁鼻器后AOB外丛状层(EPL)突触传递的变化。CSD分析揭示了EPL中的一个主要下沉(内向膜电流)。非NMDA型受体拮抗剂CNQX可阻断丘脑EPL内的突触，而NMDA型受体拮抗剂D-AP-5则不能阻断，提示二尖瓣上的非NMDA型受体参与了颗粒细胞树-树突触的调节。我们还证实了AOB的投射激活了杏仁核的兴奋性氨基酸受体和视前内侧区的CCK-B受体，从而引起结节漏斗多巴胺能神经元的兴奋。较少

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