Institute of Clinical Neuroanatomy, Goethe-University Frankfurt, NeuroScience Center, D-60590 Frankfurt am Main, Germany.
Cereb Cortex. 2011 Feb;21(2):357-67. doi: 10.1093/cercor/bhq100. Epub 2010 Jun 7.
The postsynaptic adhesion protein neuroligin-2 (NL2) is selectively localized at inhibitory synapses. Here, we studied network activity in the dentate gyrus of NL2-deficient mice following perforant path (PP) stimulation in vivo. We found a strong increase in granule cell (GC) excitability. Furthermore, paired-pulse inhibition (PPI) of the population spike, a measure for γ-aminobutyric acid (GABA)ergic network inhibition, was severely impaired and associated with reduced GABA(A) receptor (GABA(A)R)-mediated miniature inhibitory postsynaptic currents recorded from NL2-deficient GCs. In agreement with these functional data, the number of gephyrin and GABA(A)R clusters was significantly reduced in the absence of NL2, indicating a loss of synaptic GABA(A)Rs from the somata of GCs. Computer simulations of the dentate network showed that impairment of perisomatic inhibition is able to explain the electrophysiological changes observed in the dentate circuitry of NL2 knockout animals. Collectively, our data demonstrate for the first time that deletion of NL2 increases excitability of cortical neurons in the hippocampus of intact animals, most likely through impaired GABA(A)R clustering.
突触后黏附蛋白 neuroligin-2 (NL2) 选择性定位于抑制性突触。在此，我们研究了 NL2 缺失小鼠在体内穿通纤维（PP）刺激后的齿状回网络活动。我们发现颗粒细胞（GC）兴奋性明显增强。此外，群体锋电位的成对脉冲抑制（PPI），即 GABA 能网络抑制的一种测量方法，严重受损，与从 NL2 缺失 GC 记录的 GABA(A) 受体 (GABA(A)R) 介导的微小抑制性突触后电流减少有关。与这些功能数据一致，在没有 NL2 的情况下，神经胶质原纤维酸性蛋白和 GABA(A)R 簇的数量显著减少，表明 GABA(A)R 从 GC 体丢失。齿状回网络的计算机模拟表明，体旁抑制的损害能够解释 NL2 敲除动物齿状回电路中观察到的电生理变化。总的来说，我们的数据首次表明，NL2 的缺失增加了完整动物海马皮质神经元的兴奋性，很可能是通过 GABA(A)R 簇的受损。
