Critical period for sensory experience-dependent survival of newly generated granule cells in the adult mouse olfactory bulb
Critical period for sensory experience-dependent survival of newly generated granule cells in the adult mouse olfactory bulb
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DOI：
10.1073/pnas.0406082102
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发表时间：
2005-07-05
影响因子：
11.1
通讯作者：
Mori, K
中科院分区：
文献类型：
--
作者：
Yamaguchi, M;Mori, K
嗅球(OB)中的颗粒细胞不断产生并加入到成人大脑的神经元回路中。对OB的感觉输入在新生颗粒细胞的存活中起着关键作用。在这里，我们在成年小鼠身上检查了在新颗粒细胞产生后，当它们的存活受到感觉输入的强烈影响时，是否存在一个时间窗口。BrdUrd注射标记新颗粒细胞，烧灼小鼠一侧感觉传入。在BrdUrd标记后的最初14天内，剥夺和未剥夺OBS中BrdUrd阳性颗粒细胞的数量相似。28天或以后，剥夺OB组BrdUrd阳性细胞数显著减少。烧灼第14-28天可有效减少BrdUrd阳性颗粒细胞的数量，而在此期间前后烧灼2周效果不明显。给予GABA(A)受体调节剂安定可减少BrdUrd阳性颗粒细胞的数量。安定给药在第14-28天最有效。组织化学检查显示，感觉剥夺或安定诱导的颗粒细胞中caspase-3的激活伴随着细胞的凋亡。活化的caspase-3和BrdUrd双重标记表明，14-20天的颗粒细胞最容易死亡。这些结果表明，存在一个临界期，以感觉经验依赖的方式决定新颗粒细胞的存活，药物操作可以模拟感觉剥夺的效果。
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.