Adeno-associated viral overexpression of neuroligin 2 in the mouse hippocampus enhances GABAergic synapses and impairs hippocampal-dependent behaviors.
Adeno-associated viral overexpression of neuroligin 2 in the mouse hippocampus enhances GABAergic synapses and impairs hippocampal-dependent behaviors.
复制标题
小鼠海马中神经肽 2 的腺相关病毒过度表达会增强 GABA 能突触并损害海马依赖性行为。
DOI：
10.1016/j.bbr.2018.12.052
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发表时间：
2019
影响因子：
2.7
通讯作者：
Naegele, J.
中科院分区：
文献类型：
--
作者：
Van Zandt, M;Weiss, E;Almyasheva, A;Lipior, S;Maisel, S;Naegele, J.
细胞粘附分子neuroligin 2（NLGN 2）调节GABA能突触的发育，但其在成年海马神经回路功能中的作用尚不清楚。我们研究了病毒载体介导的NLGN 2过表达后的GABA能突触和海马依赖性行为。用AAV-NLGN 2转导海马神经元增加了NLGN 2的神经元表达以及GABA能突触后蛋白gephyrin和GABAARγ2以及突触前囊泡GABA转运蛋白（VGAT）的膜定位，表明GABA能突触的跨突触增强。与此相反，突触后密度蛋白-95（PSD-95）和突触前囊泡谷氨酸转运蛋白（VGLUT）蛋白质是不变的。此外，AAV-NLGN 2显著增加与突触后桥蛋白+斑点共定位的小清蛋白免疫反应性（PV+）突触结。此外，这些变化被证明会导致认知障碍，如一系列依赖于记忆的任务和社会行为所示。
The cell adhesion molecule neuroligin2 (NLGN2) regulates GABAergic synapse development, but its role in neural circuit function in the adult hippocampus is unclear. We investigated GABAergic synapses and hippocampus-dependent behaviors following viral-vector-mediated overexpression of NLGN2. Transducing hippocampal neurons with AAV-NLGN2 increased neuronal expression of NLGN2 and membrane localization of GABAergic postsynaptic proteins gephyrin and GABAARγ2, and presynaptic vesicular GABA transporter protein (VGAT) suggesting trans-synaptic enhancement of GABAergic synapses. In contrast, glutamatergic postsynaptic density protein-95 (PSD-95) and presynaptic vesicular glutamate transporter (VGLUT) protein were unaltered. Moreover, AAV-NLGN2 significantly increased parvalbumin immunoreactive (PV+) synaptic boutons co-localized with postsynaptic gephyrin+puncta. Furthermore, these changes were demonstrated to lead to cognitive impairments as shown in a battery of hippocampal-dependent mnemonic tasks and social behaviors.