Khazipov R N, Zefirov A L, Ben-Ari E
Kazan Medical University.
Usp Fiziol Nauk. 1998 Apr-Jun;29(2):55-67.
GABA is the principal neurotransmitter of inhibition in the adult mammalian brain. However, at early stages of development, including embryonic period and first week of postnatal life, GABA plays the role of main neurotransmitter of excitation. The paradoxical excitatory effect of GABA is due to an inversed chloride gradient and therefore a depolarizing direction of GABA-A receptor mediated responses. In addition, another type of GABAergic inhibition mediated by postsynaptic GABA-B receptors is not functional at early stage of life. In the neonatal rat hippocampus, GABA, acting via GABA-A receptors, activates voltage gated sodium and calcium channels and potentiates the activity of NMDA receptors by reducing their voltage dependent Mg2+ block. The temporal window when GABA exerts excitatory actions coincides with a particular pattern of activity of hippocampal neuronal network that is characterized by periodical giant depolarizing potentials (GDPs) reminiscent of interictal-like epileptiform discharges. Recent studies have shown that GDPs result from the synchronous discharge of GABAergic interneurons and principal glutamatergic pyramidal cells and are mediated by the synergistic excitatory actions of GABA-A and glutamate receptors. GDPs provide synchronous intracellular Ca2+ oscillations and may therefore be implicated in hebbian modulation of developing synapses and activity-dependent formation of the hippocampal network.
γ-氨基丁酸(GABA)是成年哺乳动物大脑中主要的抑制性神经递质。然而,在发育的早期阶段,包括胚胎期和出生后第一周,GABA发挥着主要兴奋性神经递质的作用。GABA这种矛盾的兴奋作用是由于氯离子梯度反转,因此GABA-A受体介导的反应呈去极化方向。此外,另一种由突触后GABA-B受体介导的GABA能抑制在生命早期并不起作用。在新生大鼠海马体中,通过GABA-A受体起作用的GABA可激活电压门控钠通道和钙通道,并通过减少电压依赖性Mg2+阻滞来增强NMDA受体的活性。GABA发挥兴奋作用的时间窗口与海马神经元网络的一种特定活动模式相吻合,这种模式的特征是周期性巨大去极化电位(GDPs),类似于发作间期样癫痫样放电。最近的研究表明,GDPs是由GABA能中间神经元和主要的谷氨酸能锥体细胞同步放电产生的,并由GABA-A和谷氨酸受体的协同兴奋作用介导。GDPs提供同步的细胞内Ca2+振荡,因此可能参与发育中突触的赫布调制和海马网络的活动依赖性形成。