Institute of Clinical Neuroanatomy, Neuroscience Center, Goethe University Frankfurt, 60590 Frankfurt am Main, Germany
Faculty of Biosciences, Goethe University Frankfurt, 60439 Frankfurt am Main, Germany.
eNeuro. 2023 Apr 20;10(4). doi: 10.1523/ENEURO.0471-22.2023. Print 2023 Apr.
Loss-of-function mutations in neuroligin-4 (Nlgn4), a member of the neuroligin family of postsynaptic adhesion proteins, cause autism spectrum disorder in humans. Nlgn4 knockout (KO) in mice leads to social behavior deficits and complex alterations of synaptic inhibition or excitation, depending on the brain region. In the present work, we comprehensively analyzed synaptic function and plasticity at the cellular and network levels in hippocampal dentate gyrus of Nlgn4 KO mice. Compared with wild-type littermates, adult Nlgn4 KO mice exhibited increased paired-pulse inhibition of dentate granule cell population spikes, but no impairments in excitatory synaptic transmission or short-term and long-term plasticity patch-clamp recordings in neonatal organotypic entorhino-hippocampal slice cultures from Nlgn4 KO and wild-type littermates revealed no significant differences in excitatory or inhibitory synaptic transmission, homeostatic synaptic plasticity, and passive electrotonic properties in dentate granule cells, suggesting that the increased inhibition is the result of altered network activity in the adult Nlgn4 KO. A comparison with prior studies on Nlgn 1-3 knock-out mice reveals that each of the four neuroligins exerts a characteristic effect on both intrinsic cellular and network activity in the dentate gyrus .
神经黏附素家族成员 neuroligin-4 (Nlgn4) 的功能丧失突变会导致人类出现自闭症谱系障碍。在小鼠中敲除 Nlgn4 会导致社交行为缺陷以及突触抑制或兴奋的复杂改变，具体取决于大脑区域。在本工作中，我们全面分析了 Nlgn4 KO 小鼠海马齿状回在细胞和网络水平上的突触功能和可塑性。与野生型同窝仔相比，成年 Nlgn4 KO 小鼠表现出齿状回颗粒细胞群体锋电位的成对脉冲抑制增加，但在兴奋性突触传递或短期和长期可塑性方面没有损伤 在来自 Nlgn4 KO 和野生型同窝仔的新生器官型内嗅-海马切片培养物中的膜片钳记录显示，兴奋性或抑制性突触传递、同型突触可塑性和齿状回颗粒细胞的被动电紧张性质没有显著差异，这表明增加的抑制是成年 Nlgn4 KO 中改变的网络活动的结果。与之前关于 Nlgn1-3 敲除小鼠的研究进行比较表明，四种神经黏附素中的每一种都对齿状回中的内在细胞和网络活动产生特征性影响。
