Department of Neurology, David Geffen School of Medicine at the University of California, Los Angeles, California, USA.
Nat Neurosci. 2010 Feb;13(2):205-12. doi: 10.1038/nn.2464. Epub 2009 Dec 20.
Gamma-frequency oscillations depend on phasic synaptic GABA(A) receptor (GABA(A)R)-mediated inhibition to synchronize spike timing. The spillover of synaptically released GABA can also activate extrasynaptic GABA(A)Rs, and such tonic inhibition may also contribute to modulating network dynamics. In many neuronal cell types, tonic inhibition is mediated by delta subunit-containing GABA(A)Rs. We found that the frequency of in vitro cholinergically induced gamma oscillations in the mouse hippocampal CA3 region was increased by the activation of NMDA receptors (NMDARs) on interneurons. The NMDAR-dependent increase of gamma oscillation frequency was counteracted by the tonic inhibition of the interneurons mediated by delta subunit-containing GABA(A)Rs. Recordings of synaptic currents during gamma activity revealed that NMDAR-mediated increases in oscillation frequency correlated with a progressive synchronization of phasic excitation and inhibition in the network. Thus, the balance between tonic excitation and tonic inhibition of interneurons may modulate gamma frequency by shaping interneuronal synchronization.
伽马频率振荡依赖于阶段性突触 GABA(A) 受体 (GABA(A)R) 介导的抑制作用来同步尖峰时间。突触释放的 GABA 也可以激活 extrasynaptic GABA(A)R，这种紧张性抑制也可能有助于调节网络动态。在许多神经元细胞类型中，紧张性抑制由 delta 亚基包含的 GABA(A)R 介导。我们发现，在体外，通过激活神经元间 NMDA 受体 (NMDAR)，可增加小鼠海马 CA3 区的胆碱能诱导的伽马振荡频率。NMDAR 依赖性伽马振荡频率增加被由 delta 亚基包含的 GABA(A)R 介导的神经元间紧张性抑制所抵消。在伽马活动期间记录突触电流表明，NMDAR 介导的振荡频率增加与网络中阶段性兴奋和抑制的逐步同步相关。因此，神经元间紧张性兴奋和紧张性抑制的平衡可能通过塑造神经元间的同步来调节伽马频率。
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