Spontaneous development of synchronous oscillatory activity during maturation of cortical networks in vitro
Spontaneous development of synchronous oscillatory activity during maturation of cortical networks in vitro
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DOI：
10.1152/jn.00316.2002
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发表时间：
2002-11-01
影响因子：
2.5
通讯作者：
Voigt, T
中科院分区：
文献类型：
--
作者：
Opitz, T;De Lima, AD;Voigt, T
最近的研究集中在新皮层早期发育过程中自发性大规模波动活动的机制。在这项研究中，我们描述和表征同步神经元活动，发生在培养的皮质网络自然没有药物干预。可以通过Fluo-3荧光成像检测到的同步活动在培养的第二周开始时开始发展，并最终包括约1周后的整个神经元群体。神经元群体中[Ca 2 +]（i）的同步增加与单细胞中记录的长时间去极化上的动作电位爆发有关。提示这种去极化是由突触电流直接引起的，而突触电流至少由AMPA、N-甲基-D-天冬氨酸（NMDA）和GABA（A）受体介导的三种不同成分组成。我们从未观察到一个逐渐去极化的起搏电位，也没有发现在爆发间期兴奋性改变的证据。然而，我们发现证据表明，在爆发后，突触会出现一段时间的抑制。网络兴奋性在几秒钟内从这种抑郁中逐渐恢复，这可以解释自发网络活动的偶发性。使用药理学操作来研究网络中活动的传播，我们表明，在很短的时间内，同步网络活动取决于多巴胺能和GABA（A）能神经传递。GABA（A）受体介导的电流在培养1周和2周时的再极化电位均显著高于静息膜电位，提示GABA的去极化作用。然而，在2周以上的培养物中，GABA（A）受体的抑制不会导致同步网络活动的阻断，但会导致突发宽度和频率的调制。
Recent studies have focused attention on mechanisms of spontaneous large-scale wavelike activity during early development of the neocortex. In this study, we describe and characterize synchronous neuronal activity that occurs in cultured cortical networks naturally without pharmacological intervention. The synchronous activity that can be detected by means of Fluo-3 fluorescence imaging starts to develop at the beginning of the second week in culture and eventually includes the entire neuronal population about 1 wk later. A synchronous increase of [Ca2+](i) in the neuronal population is associated with a burst of action potentials riding on a long-lasting depolarization recorded in a single cell. It is suggested that this depolarization results directly from synaptic current, which was comprised of at least three different components mediated by AMPA, N-methyl-D-aspartate (NMDA), and GABA(A) receptors. We never observed a gradually depolarizing pacemaker potential and found no evidence for a change of excitability during inter-burst periods. However, we found evidence for a period of synaptic depression after bursts. Network excitability recovers gradually over seconds from this depression that can explain the episodic nature of spontaneous network activity. Using pharmacological manipulation to investigate the propagation of activity in the network, we show that synchronous network activity depends on both glutamatergic and GABA(A) ergic neurotransmission during a brief period. Reversal potential of GABA(A) receptor-mediated current was found to be significantly more positive than resting membrane potential both at 1 and 2 wk in culture, suggesting depolarizing action of GABA. However, in cultures older than 2 wk, inhibition of GABA(A) receptors does not result in block of synchronous network activity but in modulation of burst width and frequency.