A critical period for activity-dependent synaptic development during olfactory bulb adult neurogenesis.
A critical period for activity-dependent synaptic development during olfactory bulb adult neurogenesis.
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DOI：
10.1523/jneurosci.2406-09.2009
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发表时间：
2009-09-23
期刊：
影响因子：
--
通讯作者：
Lois C
中科院分区：
文献类型：
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作者：
Kelsch W;Lin CW;Mosley CP;Lois C
新的神经元在整个生命过程中大量整合到成熟的嗅球回路中。控制成年神经元突触发育及其连接的因素在很大程度上仍然未知。我们研究了活动依赖性机制在成年神经元突触发育中的作用，通过操纵感觉输入或细胞内在兴奋性的突触遗传标记。在新生神经元发育出大部分突触的过程中，感觉剥夺引起了输入和输出突触密度的显著变化。相反，当感觉剥夺开始后，突触形成完成，输入突触增加在一个域没有检测到的变化，在其他树突域。然后，我们研究了通过传递触发长去极化的电压门控钠通道来遗传性地提高新神经元的内在兴奋性对其突触发育的影响。令人惊讶的是，遗传增加兴奋性并不影响突触的发育，但挽救了由感觉剥夺引起的突触能输入突触的变化。这些实验表明，在成年神经发生过程中，在嗅球突触可塑性在很大程度上是有限的，在新的神经元的成熟过程中，当他们仍然形成突触的早期。添加具有这种初始短暂灵活性和长期稳定性的细胞，可以使嗅球处理信息的能力在面对不断变化的行为需求时变得灵活和可靠。
New neurons integrate in large numbers into the mature olfactory bulb circuit throughout life. The factors controlling the synaptic development of adult-born neurons and their connectivity remain largely unknown. We examined the role of activity-dependent mechanisms in the synaptic development of adult-born neurons by genetic labeling of synapses while manipulating sensory input or cell-intrinsic excitability. Sensory deprivation induced marked changes in the density of input and output synapses during the period when new neurons develop most of their synapses. In contrast, when sensory deprivation started after synaptic formation was complete, input synapses increased in one domain without detectable changes in the other dendritic domains. We then investigated the effects of genetically raising the intrinsic excitability of new neurons on their synaptic development by delivering a voltage-gated sodium channel that triggers long depolarizations. Surprisingly, genetically increasing excitability did not affect synaptic development, but rescued the changes in glutamatergic input synapses caused by sensory deprivation. These experiments show that during adult neurogenesis in the olfactory bulb synaptic plasticity is largely restricted to an early period during the maturation of new neurons when they are still forming synapses. The addition of cells endowed with such an initial short-lived flexibility and long-term stability may enable the processing of information by the olfactory bulb to be both versatile and reliable in the face of changing behavioral demands.