Adult-born neurons modify excitatory synaptic transmission to existing neurons.
Adult-born neurons modify excitatory synaptic transmission to existing neurons.
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成年神经元将兴奋性突触传播改变为现有神经元。
DOI：
10.7554/elife.19886
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发表时间：
2017-01-30
期刊：
影响因子：
7.7
通讯作者：
Overstreet-Wadiche L
中科院分区：
文献类型：
--
作者：
Adlaf EW;Vaden RJ;Niver AJ;Manuel AF;Onyilo VC;Araujo MT;Dieni CV;Vo HT;King GD;Wadiche JI;Overstreet-Wadiche L
成年出生的神经元在齿状回中不断产生，但新神经元的突触整合是否影响先前存在的回路尚不清楚。在这里，我们研究了如何操纵成年小鼠的神经发生改变兴奋性突触传递到成熟的齿状神经元。通过有条件地缺失干细胞中的促凋亡基因Bax来促进神经发生，可降低成熟神经元的兴奋性突触后电流（EPSCs）和脊柱密度，而神经发生的基因消融可增加成熟神经元的EPSCs。出乎意料的是，我们发现发育和成熟齿状神经元中Bax的缺失增加了EPSCs，并阻止了神经发生诱导的突触抑制。综上所述，这些结果表明，神经发生改变突触传递到成熟神经元的方式与先前存在的突触重新分配到新整合的神经元的方式一致，并且Bax信号通路的非凋亡功能有助于齿状回路中持续的突触完善。神经发生，即新的脑细胞神经元的产生，主要发生在出生前。然而，大脑中与记忆有关的齿状回区域在人的一生中不断产生新的神经元。最近的研究表明，在齿状回中增加神经元有助于大脑区分相似的视觉、声音和气味。这反过来又使人们更容易将相似的经历编码为不同的记忆。大脑的外层被称为皮层，它处理来自我们感官的信息，并将其连同我们在空间中的位置信息一起发送到齿状回。通过结合这种感觉和空间信息，齿状回能够产生一种独特的经验记忆。但是神经发生是如何影响这个过程的呢？当齿状回积累更多的神经元时，皮层的神经元数量保持不变。一些皮层神经元会将它们的连接——称为突触——转移到新的神经元上吗？还是大脑产生了额外的突触来容纳新生细胞？Adlaf等人着手回答这个问题，他们对小鼠进行基因改造，改变齿状回中可能形成的新神经元的数量。新生神经元数量的增加减少了皮层与齿状回成熟神经元之间的突触数量。相反，杀死新生神经元会产生相反的效果，增加与老细胞的突触连接的强度。这表明新的突触不是为了适应新的神经元而形成的，而是齿状回中新旧神经元之间突触的重新分配。需要进一步的研究来确定突触的重新分配如何影响齿状回的工作。重新分配突触会破坏现有的记忆吗？这些发现与运动的影响有什么关系——这种增加神经发生的自然方式是否增加了系统中突触的总数，从而可能为新旧神经元创造足够的连接？DOI: http://dx.doi.org/10.7554/eLife.19886.002
Adult-born neurons are continually produced in the dentate gyrus but it is unclear whether synaptic integration of new neurons affects the pre-existing circuit. Here we investigated how manipulating neurogenesis in adult mice alters excitatory synaptic transmission to mature dentate neurons. Enhancing neurogenesis by conditional deletion of the pro-apoptotic gene Bax in stem cells reduced excitatory postsynaptic currents (EPSCs) and spine density in mature neurons, whereas genetic ablation of neurogenesis increased EPSCs in mature neurons. Unexpectedly, we found that Bax deletion in developing and mature dentate neurons increased EPSCs and prevented neurogenesis-induced synaptic suppression. Together these results show that neurogenesis modifies synaptic transmission to mature neurons in a manner consistent with a redistribution of pre-existing synapses to newly integrating neurons and that a non-apoptotic function of the Bax signaling pathway contributes to ongoing synaptic refinement within the dentate circuit. DOI: http://dx.doi.org/10.7554/eLife.19886.001 Neurogenesis, the creation of new brain cells called neurons, occurs primarily before birth. However, a region of the brain called the dentate gyrus, which is involved in memory, continues to produce new neurons throughout life. Recent studies suggest that adding neurons to the dentate gyrus helps the brain to distinguish between similar sights, sounds and smells. This in turn makes it easier to encode similar experiences as distinct memories. The brain’s outer layer, called the cortex, processes information from our senses and sends it, along with information about our location in space, to the dentate gyrus. By combining this sensory and spatial information, the dentate gyrus is able to generate a unique memory of an experience. But how does neurogenesis affect this process? As the dentate gyrus accumulates more neurons, the number of neurons in the cortex remains unchanged. Do some cortical neurons transfer their connections – called synapses – to the new neurons? Or does the brain generate additional synapses to accommodate the newborn cells? Adlaf et al. set out to answer this question by genetically modifying mice to alter the number of new neurons that could form in the dentate gyrus. Increasing the number of newborn neurons reduced the number of synapses between the cortex and the mature neurons in the dentate gyrus. Conversely, killing off newborn neurons had the opposite effect, increasing the strength of the synaptic connections to older cells. This suggests that new synapses are not formed to accommodate new neurons, but rather that there is a redistribution of synapses between old and new neurons in the dentate gyrus. Further work is required to determine how this redistribution of synapses contributes to how the dentate gyrus works. Does redistributing synapses disrupt existing memories? And how do these findings relate to the effects of exercise – does this natural way of increasing neurogenesis increase the overall number of synapses in the system, potentially creating enough connections for both new and old neurons? DOI: http://dx.doi.org/10.7554/eLife.19886.002