Rhythmic intrinsic bursting neurons in human neocortex obtained from pediatric patients with epilepsy

Rhythmic intrinsic bursting neurons in human neocortex obtained from pediatric patients with epilepsy
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DOI:
10.1111/j.1460-9568.2011.07746.x
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发表时间:
2011-07
影响因子:
3.4
通讯作者:
A. Tryba;Catherine C. Kaczorowski;Faiza Ben-Mabrouk;F. Elsen;S. Lew;C. Marcuccilli
A. Tryba;Catherine C. Kaczorowski;Faiza Ben-Mabrouk;F. Elsen;S. Lew;C. Marcuccilli
中科院分区:
医学3区
文献类型:
--
作者:
A. Tryba;Catherine C. Kaczorowski;Faiza Ben-Mabrouk;F. Elsen;S. Lew;C. Marcuccilli

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新皮质振荡是突触耦合网络同步活动的结果,并可受到单个神经元内在放电特性的强烈影响。因此,单个神经元的内在电反应特性可能对整个网络功能有重要的影响。节律性固有爆发(RIB)神经元是人们特别感兴趣的,因为它们可以启动和/或强烈影响网络振荡。虽然新皮质肋骨神经元已经在多种物种中被识别,但目前的研究是第一次在人类新皮质中鉴定和表征肋骨神经元。利用全细胞电流钳记录,在切除的儿童难治性癫痫患者的新皮质组织中发现了肋神经元(n=12)。与人类规则棘波神经元(n=12)不同,人肋骨神经元在0.1-4赫兹的频率下表现出节律性的动作电位爆发。在快速兴奋性神经传递和电压门控钙通道被阻断后,这些猝发持续存在。然而,随后应用持续性钠电流(INAP)阻滞剂利鲁唑可消除猝发。在利鲁唑(10或20μm)存在的情况下,人肋骨神经元不再爆裂,而是像规则的尖峰神经元一样强直地放电。这些数据表明,INAP在观察到的人大脑皮层肋骨神经元的固有振荡活动中起关键作用。据推测,INAP表达和/或功能的异常变化最终可能导致与异常网络活动有关的神经系统疾病,如癫痫。
Neocortical oscillations result from synchronized activity of a synaptically coupled network and can be strongly influenced by the intrinsic firing properties of individual neurons. As such, the intrinsic electroresponsive properties of individual neurons may have important implications for overall network function. Rhythmic intrinsic bursting (rIB) neurons are of particular interest, as they are poised to initiate and/or strongly influence network oscillations. Although neocortical rIB neurons have been recognized in multiple species, the current study is the first to identify and characterize rIB neurons in the human neocortex. Using whole‐cell current‐clamp recordings, rIB neurons (n = 12) are identified in human neocortical tissue resected from pediatric patients with intractable epilepsy. In contrast to human regular spiking neurons (n = 12), human rIB neurons exhibit rhythmic bursts of action potentials at frequencies of 0.1–4 Hz. These bursts persist after blockade of fast excitatory neurotransmission and voltage‐gated calcium channels. However, bursting is eliminated by subsequent application of the persistent sodium current (INaP) blocker, riluzole. In the presence of riluzole (either 10 or 20 μm), human rIB neurons no longer burst, but fire tonically like regular spiking neurons. These data demonstrate that INaP plays a critical role in intrinsic oscillatory activity observed in rIB neurons in the human neocortex. It is hypothesized that aberrant changes in INaP expression and/or function may ultimately contribute to neurological diseases that are linked to abnormal network activity, such as epilepsy.