Leinekugel X, Medina I, Khalilov I, Ben-Ari Y, Khazipov R
INSERM Unité 29, Hôpital de Port-Royal, Paris, France.
Neuron. 1997 Feb;18(2):243-55. doi: 10.1016/s0896-6273(00)80265-2.
We asked whether GABA(A) and NMDA receptors may act in synergy in neonatal hippocampal slices, at a time when GABA exerts a depolarizing action. The GABA(A) receptor agonist isoguvacine reduced the voltage-dependent Mg2+ block of single NMDA channels recorded in cell-attached configuration from P(2-5) CA3 pyramidal neurons and potentiated the Ca2+ influx through NMDA channels. The synaptic response evoked by electrical stimulation of stratum radiatum was mediated by a synergistic interaction between GABA(A) and NMDA receptors. Network-driven Giant Depolarizing Potentials, which are a typical feature of the neonatal hippocampal network, provided coactivation of GABA(A) and NMDA receptors and were associated with spontaneous and synchronous Ca2+ increases in CA3 pyramidal neurons. Thus, at the early stages of development, GABA is a major excitatory transmitter that acts in synergy with NMDA receptors. This provides in neonatal neurons a hebbian stimulation that may be involved in neuronal plasticity and network formation in the developing hippocampus.
我们探讨了在γ-氨基丁酸（GABA）发挥去极化作用的时期，GABA A型和N-甲基-D-天冬氨酸（NMDA）受体在新生海马切片中是否协同发挥作用。GABA A型受体激动剂异鹅膏蕈氨酸减少了从出生后第2至5天的CA3锥体神经元以细胞贴附模式记录的单个NMDA通道的电压依赖性Mg2+阻滞，并增强了通过NMDA通道的Ca2+内流。放射层电刺激诱发的突触反应是由GABA A型和NMDA受体之间的协同相互作用介导的。网络驱动的巨大去极化电位是新生海马网络的一个典型特征，它使GABA A型和NMDA受体共同激活，并与CA3锥体神经元中自发且同步的Ca2+增加相关。因此，在发育早期，GABA是一种主要的兴奋性神经递质，与NMDA受体协同发挥作用。这在新生神经元中提供了一种赫布型刺激，可能参与发育中的海马体的神经元可塑性和网络形成。
