Neural activity is thought to play a significant role during the development of the cerebral cortex. In this study, we examined the effects of global activity block or enhancement and the effects of patterned firing on the ability of cultured rat neocortical neurons to survive during the second week in vitro, beyond the beginning of synaptogenesis. Blockade of neuronal activity by adding tetrodotoxin (TTX) and increasing magnesium concentration in the medium strongly reduced the survival of cortical cells. Increasing neuronal activity by raising the external potassium concentration significantly improved the survival of cortical neurons. We postulated that in a developing neuronal network the survival of nerve cells is regulated by synaptically mediated events that involve changes in the intracellular calcium concentration. To examine this question further, we monitored the activity of the developing network by optically recording the intracellular calcium signals of many neurons simultaneously. These recordings show that in low magnesium neocortical neurons express synchronized oscillation of their intracellular calcium concentration. The ability of a network to synchronize the changes in intracellular calcium of multiple cells appeared gradually during the second week in culture, paralleled by both an increase in the synaptic density and a decline in the number of surviving neurons. By examining the fate of identified cells several days after a recording session, we found that those nerve cells that were co-activated with other neurons had a significantly higher chance to survive than cells that did not participate in synchronized events. These experiments demonstrate that during early cortical network development cortical neurons show synchronized firing activity and that the survival of neurons is at least partially dependent on this pattern of neuronal activity.

译文

人们认为神经活动在大脑皮层的发育过程中起着重要的作用。在这项研究中,我们检查了全局活性阻滞或增强的影响以及图案化放电对培养的大鼠新皮层神经元在体外第二周(突触形成开始之后)存活的能力的影响。通过添加河豚毒素(TTX)和增加培养基中镁的浓度来阻止神经元活性,这会大大降低皮质细胞的存活率。通过提高外部钾离子浓度来增加神经元活性可以显着改善皮层神经元的存活率。我们推测,在发育中的神经元网络中,神经细胞的存活受到涉及细胞内钙浓度变化的突触介导事件的调节。为了进一步检查这个问题,我们通过光学记录许多神经元的细胞内钙信号同时监测了发育中网络的活动。这些记录表明,在低镁状态下,新皮层神经元表达其细胞内钙浓度的同步振荡。在培养的第二周内,网络同步多个细胞的细胞内钙变化的能力逐渐显现,同时突触密度增加和存活神经元数量减少。通过在录制会话几天后检查识别出的细胞的命运,我们发现与其他神经元共激活的神经细胞比不参与同步事件的细胞具有更高的存活机会。这些实验表明,在早期皮质网络发育过程中,皮质神经元显示出同步的放电活动,并且神经元的存活至少部分取决于这种神经元活动模式。

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