Sheroziya Maxim G, von Bohlen Und Halbach Oliver, Unsicker Klaus, Egorov Alexei V
Department of Neuroanatomy, University of Heidelberg, Interdisciplinary Center for Neurosciences, D-69120 Heidelberg, Germany.
J Neurosci. 2009 Sep 30;29(39):12131-44. doi: 10.1523/JNEUROSCI.1333-09.2009.
Periodic spontaneous activity represents an important attribute of the developing nervous system. The entorhinal cortex (EC) is a crucial component of the medial temporal lobe memory system. Yet, little is known about spontaneous activity in the immature EC. Here, we investigated spontaneous field potential (fp) activity and intrinsic firing patterns of medial EC layer III principal neurons in brain slices obtained from rats at the first two postnatal weeks. A fraction of immature layer III neurons spontaneously generated prolonged (2-20 s) voltage-dependent intrinsic bursting activity. Prolonged bursts were dependent on the extracellular concentration of Ca(2+) (Ca(2+)). Thus, reduction of Ca(2+) increased the fraction of neurons with prolonged bursting by inducing intrinsic bursts in regularly firing neurons. In 1 mm Ca(2+), the percentages of neurons showing prolonged bursts were 53%, 81%, and 29% at postnatal day 5 (P5)-P7, P8-P10, and P11-P13, respectively. Prolonged intrinsic bursting activity was blocked by buffering intracellular Ca(2+) with BAPTA, and by Cd(2+), flufenamic acid (FFA), or TTX, and was suppressed by nifedipine and riluzole, suggesting that the Ca(2+)-sensitive nonspecific cationic current (I(CAN)) and the persistent Na(+) current (I(Nap)) underlie this effect. Indeed, a 0.2-1 s suprathreshold current step stimulus elicited a terminated plateau potential in these neurons. fp recordings at P5-P7 showed periodic spontaneous glutamate receptor-mediated events (sharp fp events or prolonged fp bursts) which were blocked by FFA. Slow-wave network oscillations become a dominant pattern at P11-P13. We conclude that prolonged intrinsic bursting activity is a characteristic feature of developing medial EC layer III neurons that might be involved in neuronal and network maturation.
周期性自发活动是发育中的神经系统的一个重要属性。内嗅皮层(EC)是内侧颞叶记忆系统的关键组成部分。然而,关于未成熟EC中的自发活动却知之甚少。在此,我们研究了出生后前两周大鼠脑片中内侧EC III层主要神经元的自发场电位(fp)活动和内在放电模式。一部分未成熟的III层神经元自发产生持续时间较长(2 - 20秒)的电压依赖性内在爆发活动。持续爆发依赖于细胞外Ca(2+)(Ca(2+))的浓度。因此,降低Ca(2+)通过在正常放电的神经元中诱导内在爆发,增加了具有持续爆发的神经元比例。在1 mM Ca(2+)条件下,出生后第5天(P5) - P7、P8 - P10和P11 - P13时,表现出持续爆发的神经元百分比分别为53%、81%和29%。用BAPTA缓冲细胞内Ca(2+)、Cd(2+)、氟芬那酸(FFA)或TTX可阻断持续的内在爆发活动,硝苯地平和利鲁唑可抑制该活动,这表明Ca(2+)敏感的非特异性阳离子电流(I(CAN))和持续性Na(+)电流(I(Nap))是产生这种效应的基础。事实上,0.2 - 1秒的阈上电流阶跃刺激在这些神经元中引发了一个终止的平台电位。P5 - P7时的fp记录显示了周期性的自发谷氨酸受体介导事件(尖锐的fp事件或持续的fp爆发),这些事件可被FFA阻断。慢波网络振荡在P11 - P13时成为主导模式。我们得出结论,持续的内在爆发活动是发育中的内侧EC III层神经元的一个特征,可能参与神经元和网络的成熟。