Molecular mechanisms of dynamic changes in memory traces

记忆痕迹动态变化的分子机制

基本信息

批准号：
16300100
负责人：
KABA Hideto
金额：
$ 9.54万
依托单位：
Kochi University
依托单位国家：
日本
项目类别：
Grant-in-Aid for Scientific Research (B)
财政年份：
2004
资助国家：
日本
起止时间：
2004 至 2006
项目状态：
已结题

项目摘要

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.

当雌性与男性伴侣交配时，她会为男性的尿等素形成记忆，从而阻止其信息素诱导妊娠障碍。该记忆的基础神经变化发生在辅助嗅球（AOB）中，这是Vomeronasal系统中的第一个继电器，取决于AOB中Alpha2-肾上腺素能传播的增强，并涉及二列和颗粒细胞之间的相互突触的变化。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期增强诱导。我们已经建立了一种与AOB神经元共培养呕吐的程序。我们的数据表明，VSN和AOB神经元的分化和/或成熟均由共培养刺激或修改。通过检查V2R型呕吐受体（VR1和VR2）的表达以及与AOB神经元共培养的Vomeronasal器官共培养中的化学感应响应能力，我们证明AOB神经元诱导它们在VSN中诱导VSN的表达。，年轻的大鼠表现出对它们在产后第11天暴露的气味以及脚部冲击的气味的厌恶。通过注入蛋白质磷酸酶1（PP1）抑制剂，抑制剂-2在Odour-嗅球（OB）中添加抑制剂-2冲击训练，我们证明了PP1参与了厌恶嗅觉学习的灭绝过程。我们已经表明，这种嗅觉学习的长期（但不是短期的促进过程）需要环状AMP响应元件结合蛋白（CREB）及其在OB中的磷酸化。 CREB磷酸化已显示出诱导组蛋白乙酰化。在这项研究中，我们证明OB中的组蛋白乙酰化参与了这种嗅觉学习的获取过程。