Molecular mechanisms of dynamic changes in memory traces

当女性与男性伴侣交配时，她会对男性的尿液信息素形成记忆，从而防止男性的信息素导致受孕障碍。这种记忆的神经变化发生在副嗅球(AOB)，它是犁鼻系统中的第一个中继器，依赖于交配诱导的AOB中α2-肾上腺素能传递的增强，并涉及二尖瓣和颗粒细胞之间相互突触的变化。在这项研究中，我们证明了催产素促进了二尖瓣到颗粒细胞突触的长时程增强的诱导。我们建立了一种共同培养犁鼻感觉神经元(VSNs)和AOB神经元的程序。我们的数据表明，VSNs和AOB神经元的分化和/或成熟都受到共同培养的刺激或修改。通过检测与AOB神经元共同培养的犁鼻器V2R型受体(VR1和VR2)的表达和化学感觉反应，我们证明了AOB神经元诱导V2R型犁鼻器受体的表达，使其发挥作用。在出生后第12天，幼鼠对它们所暴露的气味表现出厌恶，并在出生后第11天出现足部电击。通过在气味-休克训练期间向嗅球(OB)注入蛋白磷酸酶1(PP1)抑制物-2，我们证明了PP1参与了厌恶嗅觉学习的消退过程。我们已经证明，这种嗅觉学习的长期而不是短期的促进过程需要环磷酸腺苷反应元件结合蛋白(CREB)及其在OB中的磷酸化。CREB的磷酸化已被证明可以诱导组蛋白乙酰化。在这项研究中，我们证明了OB中的组蛋白乙酰化参与了嗅觉学习的习得过程。

When a female is mated with a male partner, she forms a memory to the urinary pheromones of the male, thereby preventing his pheromones from inducing pregnancy block. The neural changes underlying this memory occur in the accessory olfactory bulb (AOB), the first relay in the vomeronasal system, depend upon mating-induced enhancement of alpha2-adrenergic transmission in the AOB and involve changes at the reciprocal synapses between mitral and granule cells. In this study, we demonstrate that oxytocin facilitates the induction of long-term potentiation at the mitral-to-granule cell synapse.We have established a procedure for the co-culture of vomeronasal sensory neurons (VSNs) with AOB neurons. Our data suggest that the differentiation and/or maturation of VSNs and AOB neurons are both stimulated or modified by the co-culture. By examining the expression of V2R-type vomeronasal receptors (VR1 and VR2) and chemosensory responsiveness in the vomeronasal organ cocultured with AOB neurons, we demonstrate that AOB neurons induce the expression of vomeronasal receptors in VSNs, allowing them to function.On postnatal day 12, young rats show an aversion to an odour to which they had been exposed along with presentations of foot shock on postnatal day 11. By infusing the protein phosphatase 1 (PP1) inhibitor, inhibitor-2 into the olfactory bulb (OB) during odour-shock training, we demonstrate that PP1 is involved in the extinction process of aversive olfactory learning. We have shown that cyclic AMP response element binding protein (CREB) and its phosphorylation in the OB are required for the long-term, but not the short-term, facilitation process of this olfactory learning. CREB phosphorylation has been shown to induce histone acetylation. In this study, we demonstrate that histone acetylation in the OB is involved in the acquisition process of this olfactory learning.