Energy substrate availability as a determinant of neuronal resting potential, GABA signaling and spontaneous network activity in the neonatal cortex in vitro
Energy substrate availability as a determinant of neuronal resting potential, GABA signaling and spontaneous network activity in the neonatal cortex in vitro
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DOI：
10.1111/j.1471-4159.2009.06506.x
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发表时间：
2010-02-01
影响因子：
4.7
通讯作者：
Zilberter, Yuri
中科院分区：
文献类型：
--
作者：
Holmgren, Carl D.;Mukhtarov, Marat;Zilberter, Yuri
虽然大脑功能对其能量供应的最终依赖是显而易见的，但基本神经元参数和网络活动如何对能量代谢偏差做出反应尚未解决。静息膜电位 (E-m) 和 GABA 诱导的阴离子电流的反转电位 (E-GABA) 是控制神经元兴奋性的最基本参数之一。然而，尽管众所周知代谢危机可能导致神经元过度兴奋和神经元网络活动异常，但代谢应激条件下 E-m 和 E-GABA 的变化尚未得到充分记录。在这项工作中，我们表明，在切片中，能量底物的可用性决定了新生儿新皮质和海马中的 GABA 信号传导是否表现出抑制或兴奋模式。我们证明，在新生儿大脑中，E-m 和 E-GABA 强烈依赖于能量底物库的组成。用酮体、丙酮酸或乳酸补充葡萄糖会导致 E-m 和 E-GABA 显着超极化，并诱导 GABA 能突触传递模式向网络抑制的根本转变。目前被认为是体外自发新生儿网络活动标志的巨大去极化电位的产生在富含能量底物的溶液中的新皮质和海马中均受到强烈抑制。根据这些结果，我们建议人工脑脊液的成分与体内能量底物池更相似。我们的结果表明，能量不足会引起 E-m 和 E-GABA 的不利变化，导致神经元过度活跃
While the ultimate dependence of brain function on its energy supply is evident, how basic neuronal parameters and network activity respond to energy metabolism deviations is unresolved. The resting membrane potential (E-m) and reversal potential of GABA-induced anionic currents (E-GABA) are among the most fundamental parameters controlling neuronal excitability. However, alterations of E-m and E-GABA under conditions of metabolic stress are not sufficiently documented, although it is well known that metabolic crisis may lead to neuronal hyper-excitability and aberrant neuronal network activities. In this work, we show that in slices, availability of energy substrates determines whether GABA signaling displays an inhibitory or excitatory mode, both in neonatal neocortex and hippocampus. We demonstrate that in the neonatal brain, E-m and E-GABA strongly depend on composition of the energy substrate pool. Complementing glucose with ketone bodies, pyruvate or lactate resulted in a significant hyperpolarization of both E-m and E-GABA, and induced a radical shift in the mode of GABAergic synaptic transmission towards network inhibition. Generation of giant depolarizing potentials, currently regarded as the hallmark of spontaneous neonatal network activity in vitro, was strongly inhibited both in neocortex and hippocampus in the energy substrate enriched solution. Based on these results we suggest the composition of the artificial cerebrospinal fluid, which bears a closer resemblance to the in vivo energy substrate pool. Our results suggest that energy deficits induce unfavorable changes in E-m and E-GABA, leading to neuronal hyperactivity