Analysis of mechanisms of pheromonal memory formation

信息素记忆形成机制分析

基本信息

批准号：
10460133
负责人：
KABA Hideto
金额：
$ 8.51万
依托单位：
Kochi Medical School
依托单位国家：
日本
项目类别：
Grant-in-Aid for Scientific Research (B).
财政年份：
1998
资助国家：
日本
起止时间：
1998 至 2000
项目状态：
已结题

项目摘要

When female mice were mated, they form an olfactory memory to the pheromones of the mating male. The neural changes underlying this memory occur in the accessory olfactory bulb (AOB), depend upon mating-induced release of noradrenaline (NA) in the AOB and involve changes at the reciprocal synapses between mitral and granule cells. In this study we have obtained the following results.1. In situ hybridization experiments suggest that there is a pheromone-specific activation of neuronal nitric oxide synthase mRNA in the AOB during memory formation which may regulate intermediate synaptic processes.2. Using slices of the mouse AOB, we demonstrated opposite roles for N-methyl-D-aspartate receptors and group II metabotropic glutamate receptors in the dendrodendritic feedback inhibition of AOB mitral cells.3. In vivo electrophysiological experiments showed that vaginocervical stimulation enhances the activity of AOB mitral cells through a reduction in reciprocal dendrodendritic inhibition.4. Behavioural and immunohistochemical analyses demonstrated an important role for glial cells in the formation of pheromonal memory. In addition, we showed immunohistochemical expression patterns of glutamine synthetase and microglia-specific ionized calcium binding adaptor protein (Iba 1) in the mouse olfactory bulb.5. As a further step in exploring the detailed mechanisms underlying the pheromonal memory, we have simplified the analysis of neuronal circuit by reconstituting the dendrodendritic synapse between mitral and granule cells in primary dissociated cultures of AOB neurons. Using this in vitro system, we demonstrated that NA reduces GABAergic inhibitory postsynaptic currents in mitral cells by a presynaptic mechanism.6. In vivo and in vitro electrophysiological experiments demonstrated modulatory actions of the neurosteroid dehydroepiandrosterone and oxytocin on synaptic transmission between mitral and granule cells in the olfactory bulb.

当雌性小鼠交配时，它们会对交配雄性的信息素形成嗅觉记忆。这种记忆背后的神经变化发生在副嗅球 (AOB) 中，取决于交配诱导的 AOB 中去甲肾上腺素 (NA) 的释放，并涉及二尖瓣细胞和颗粒细胞之间相互突触的变化。本研究得到以下结果： 1．原位杂交实验表明，在记忆形成过程中，神经元一氧化氮合酶mRNA存在信息素特异性激活，可能调节中间突触过程。2．利用小鼠AOB切片，我们证明了N-甲基-D-天冬氨酸受体和II类代谢型谷氨酸受体在AOB二尖瓣细胞的树突反馈抑制中发挥相反的作用。3．体内电生理实验表明，阴道宫颈刺激通过减少树突状细胞的相互抑制，增强AOB二尖瓣细胞的活性。 4．行为和免疫组织化学分析证明神经胶质细胞在信息素记忆的形成中发挥重要作用。此外，我们还显示了小鼠嗅球中谷氨酰胺合成酶和小胶质细胞特异性离子钙结合蛋白（Iba 1）的免疫组织化学表达模式。5．作为探索信息素记忆背后详细机制的进一步步骤，我们通过在 AOB 神经元原代分离培养物中重建二尖瓣和颗粒细胞之间的树突突触，简化了神经元回路的分析。使用这个体外系统，我们证明NA通过突触前机制减少二尖瓣细胞中GABA能抑制性突触后电流。6．体内和体外电生理学实验证明神经类固醇脱氢表雄酮和催产素对嗅球二尖瓣和颗粒细胞之间的突触传递具有调节作用。