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

神经活动被认为在大脑皮层发育过程中起着重要作用。在这项研究中,我们研究了整体活动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 (突触开始后) 存活的能力的影响。通过添加河豚毒素 (TTX) 和增加培养基中的镁浓度来阻断神经元活性,从而大大降低了皮质细胞的存活。通过提高外部钾浓度来增加神经元活性,显着改善了皮质神经元的存活。我们推测,在发育中的神经元网络中,神经细胞的存活受到突触介导的事件的调节,这些事件涉及细胞内钙浓度的变化。为了进一步研究这个问题,我们通过同时光学记录许多神经元的细胞内钙信号来监测发育网络的活动。这些记录表明,在低镁的新皮层神经元中,其细胞内钙浓度表达同步振荡。在培养的第二周,网络使多个细胞的细胞内钙的变化同步的能力逐渐出现,同时突触密度增加和存活神经元数量减少。通过在记录过程几天后检查已识别细胞的命运,我们发现与其他神经元共同激活的神经细胞比不参与同步事件的细胞存活的机会要高得多。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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