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首页> 外文期刊>Proceedings of the National Academy of Sciences of the United States of America >Critical period for sensory experience-dependent survival of newly generated granule cells in the adult mouse olfactory bulb
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Critical period for sensory experience-dependent survival of newly generated granule cells in the adult mouse olfactory bulb

机译:成年小鼠嗅球中新生颗粒细胞的感官体验依赖生存的关键时期

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Granule cells in the olfactory bulb (OB) are continually produced and added into the neuronal circuit in the adult brain. Sensory input to the OB plays a key role in the survival of newly generated granule cells. Here, we examined in the adult mice whether there is a time window after the generation of new granule cells when their survival is strongly influenced by sensory input. New granule cells were labeled by BrdUrd injection, and the mice were deprived of sensory input unilaterally by naris cauterization. During the initial 14 days after BrdUrd labeling, the number of BrdUrd-positive granule cells was similar for deprived and undeprived OBs. At 28 days or later, the BrdUrd-positive cell number remarkably decreased in the deprived OB. Cauterization at days 14-28 effectively reduced the number of BrdUrd-positive granule cells, whereas 2-week cauterization before or after this period produced little effect. Administration of diazepam, a GABA(A) receptor modulator, decreased the number of BrdUrd-positive granule cells. The diazepam administration was most effective at days 14-28. Histochemical examination showed that activation of caspase-3 was accompanied by apoptotic cell death of granule cells that was induced by sensory deprivation or diazepam administration. Double labeling with activated caspase-3 and BrdUrd indicated that granule cells at days 14-20 were most susceptible to cell death. These results indicate that there is a critical period when the survival of new granule cells is determined in a sensory experience-dependent manner and that the pharmacological manipulation can mimic the effect of sensory deprivation.
机译:嗅球(OB)中的颗粒细胞不断产生,并被添加到成人大脑的神经元回路中。 OB的感觉输入在新产生的颗粒细胞的存活中起关键作用。在这里,我们检查了成年小鼠中新颗粒细胞产生后是否存在时间窗口,当它们的存活受到感觉输入的强烈影响时。通过BrdUrd注射标记新的颗粒细胞,并通过鼻孔烧灼法单方面剥夺小鼠的感觉输入。在BrdUrd标记后的最初14天内,被剥夺和未剥夺的OB的BrdUrd阳性颗粒细胞数量相似。在28天或更晚时,剥夺的OB中BrdUrd阳性细胞数明显减少。在第14-28天进行电灼可有效减少BrdUrd阳性颗粒细胞的数量,而在此期间之前或之后进行2周的电灼效果不明显。地西epa(一种GABA(A)受体调节剂)的给药减少了BrdUrd阳性颗粒细胞的数量。地西epa的给药在第14-28天最为有效。组织化学检查表明,caspase-3的激活伴随着由感觉剥夺或地西epa给药引起的颗粒细胞凋亡性细胞死亡。激活的caspase-3和BrdUrd的双重标记表明,第14-20天的颗粒细胞最容易死亡。这些结果表明,在一个关键时期,以感觉依赖的方式确定新颗粒细胞的存活,并且药理操作可以模仿感觉剥夺的影响。

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