Early expression of odorant receptors distorts the olfactory circuitry.
Early expression of odorant receptors distorts the olfactory circuitry.
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DOI：
10.1523/jneurosci.1502-10.2010
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发表时间：
2010-07-07
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通讯作者：
Ryba NJ
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作者：
Nguyen MQ;Marks CA;Belluscio L;Ryba NJ
哺乳动物嗅觉感觉神经元 (OSN) 的气味反应特性是由一个非常大的气味受体 (OR) 家族中单个成员的严格调控表达决定的。 OR 在将表达特定受体的所有 OSN 的中心投影聚焦到每个嗅球 (OB) 中的一对刻板位置（肾小球）方面也发挥着重要作用，从而在大脑中创建气味反应的空间图。在这里，我们表明，当在神经发育后期启动时，几乎所有 OSN 中的一个 OR 的转基因表达对 OB 的结构几乎没有影响。相比之下，50-70% OSN 中的早期 OR 转基因表达（由 Gγ8 启动子介导）严重扭曲了肾小球的形态，并改变了许多不表达转基因的残留 OSN 的投影模式。有趣的是，尽管嗅觉神经发生下降时 Gγ8 和转基因 OR 表达下调，但这种靶向破坏在成年动物中仍然存在。事实上，功能成像研究表明，成年 Gγ8 转基因 OR 小鼠对气味反应的复杂性显着降低。因此，我们表明，在 OSN 发育早期转基因 OR 表达的启动，而不仅仅是转基因表达的程度，决定了其改变 OB 解剖结构和功能的有效性。总而言之，这些数据意味着 OR 表达时间需要非常严格地控制，以实现哺乳动物嗅觉系统的精确接线和功能。
The odor response properties of a mammalian olfactory sensory neuron (OSN) are determined by the tightly regulated expression of a single member of a very large family of odorant receptors (ORs). The OR also plays an important role in focusing the central projections of all OSNs expressing that particular receptor to a pair of stereotypic locations (glomeruli) in each olfactory bulb (OB), thus creating a spatial map of odor responses in the brain. Here we show that when initiated late in neural development, transgenic expression of one OR in almost all OSNs has little influence on the architecture of the OB. In contrast, early OR-transgene expression (mediated by the Gγ8-promoter) in 50–70% of OSNs grossly distorts the morphology of glomeruli and alters the projection patterns of many residual OSNs not expressing the transgene. Interestingly, this disruption of targeting persists in adult animals despite down-regulation of Gγ8 and transgenic OR expression that occurs as olfactory neurogenesis declines. Indeed, functional imaging studies reveal a dramatic decrease in the complexity of responses to odorants in adult Gγ8-transgenic OR mice. Thus, we show that initiation of transgenic OR-expression early in the development of OSNs, rather than just the extent of transgene expression, determines its effectiveness at modifying OB anatomy and function. Taken together these data imply that OR-expression timing needs to be very tightly controlled to achieve the precise wiring and function of the mammalian olfactory system.