Molecular mechanisms of an olfactory memory relevant to species survival

雌性老鼠对与之交配的雄性老鼠的信息素形成嗅觉记忆。这种嗅觉记忆在生物学上是至关重要的，因为它可以防止任何随后暴露于雄性信息素的触发神经内分泌机制，从而终止妊娠。来自未形成记忆的陌生雄性的信息素，通过犁鼻感受器激活副嗅觉系统，诱导怀孕阻滞。记忆的形成依赖于交配时的宫颈阴道刺激，但需要在交配后立即长时间暴露于雄性信息素4至6小时。记忆的形成依赖于交配诱导的副嗅球（AOB）去甲肾上腺素能末端的激活，AOB是副嗅通路的第一个中继。这种记忆在交配后至少持续30天。这种记忆形成背后的突触变化发生在脑后皮层。在AOB中，二尖瓣细胞被矢状鼻神经输入激活后，通过树突突触释放谷氨酸而沉积更大的颗粒细胞。这种去极化从颗粒细胞中释放出γ -氨基丁酸，从而使二尖瓣细胞超极化。最近的研究表明二尖瓣到颗粒树突突触参与记忆的形成。在这项研究中，我们得到了以下结果：外源性一氧化氮可以在没有交配的情况下诱导信息素特异性嗅觉记忆，这种记忆至少部分是由去甲肾上腺素介导的。此外，内源性一氧化氮合酶活性的激活也产生同样的效果。在与博士合作。Ichikawa， Mori和Matsuoka，我们证明了二尖瓣到颗粒的不对称突触的大小在已经形成记忆的组中明显大于没有形成记忆的组。我们之前已经证明，在AOB中激活mGluR2（一种代谢性谷氨酸受体）可以形成信息素特异性记忆。初步实验表明，缺乏mGluR2的小鼠嗅觉记忆受损。少

Female mice form an olfactory memory of the pheromones of the male with which they mate. This olfactory memory is of critical biological importance, because it prevents any subsequent exposure to this male's pheromones from initiating neuroendocrine mechanisms that would terminate pregnancy. Pheromones from strange males, for which no memory has been formed, induce pregnacy block by activating the accessory olfactory system by way of the vomeronasal receptors. Memory formation depends on cervicovaginal stimulation at mating, but requires a prolonged exposure of 4 to 6 h to male phernomones immediately after mating. The memory formation depends on mating-induced activation of noradrenergic terminals in the accessory olfactory bulb (AOB), the first relay in the accessory olfactory pathway. This memory lasts for at least 30 days following mating. The synaptic changes underlying this memory formation occur in the AOB.In the AOB,mitral cells, when activated by vomeronasal nerve inputs, depo … More larize granule cells by means of glutamate released at the dendrodendritic synapses. This depolarization releases gamma-aminobutyric acid from the granule cells which in turn hyperpolarize the mitral cells. Recent studies have implicated the mitral-to-granule dendrodendritic synapse in the formation of the memory. In this study we have obtained the following results.1.Exogenous administration of nitric oxide can induce a pheromone-specific olfactory memory without mating, and that this memory is mediated, at least in part, by noradrenaline. In addition, activation of endogenous nitric oxide synthase activity produces the same effect.2.In collaboration with Drs.Ichikawa, Mori and Matsuoka, we demonstrate that the size of the mitral-to-granule asymmetrical synapse is significantly larger in the group that has formed the memory than in the group that has not formed the memory.3.We have previously demonstrated that activation of mGluR2, a metabotropic glutamate receptor, in the AOB permits the formation of a pheromone-specific memory. Preliminary experiments suggest impairment of the olfactory memory in mice lacking mGluR2. Less