Department of Cellular and Molecular Physiology, Department of Neuroscience, Yale University School of Medicine, New Haven, United States.
Department of Health Sciences, School of Medicine, Hokkaido University, Sapporo, Japan.
Elife. 2021 Oct 18;10:e59613. doi: 10.7554/eLife.59613.
Ionotropic neurotransmitter receptors at postsynapses mediate fast synaptic transmission upon binding of the neurotransmitter. Post- and trans-synaptic mechanisms through cytosolic, membrane, and secreted proteins have been proposed to localize neurotransmitter receptors at postsynapses. However, it remains unknown which mechanism is crucial to maintain neurotransmitter receptors at postsynapses. In this study, we ablated excitatory or inhibitory neurons in adult mouse brains in a cell-autonomous manner. Unexpectedly, we found that excitatory AMPA receptors remain at the postsynaptic density upon ablation of excitatory presynaptic terminals. In contrast, inhibitory GABA receptors required inhibitory presynaptic terminals for their postsynaptic localization. Consistent with this finding, ectopic expression at excitatory presynapses of neurexin-3 alpha, a putative trans-synaptic interactor with the native GABA receptor complex, could recruit GABA receptors to contacted postsynaptic sites. These results establish distinct mechanisms for the maintenance of excitatory and inhibitory postsynaptic receptors in the mature mammalian brain.
离子型递质受体位于突触后，在递质结合后介导快速突触传递。通过细胞质、膜和分泌蛋白的突触后和突触前机制被提出将递质受体定位于突触后。然而，哪种机制对于维持突触后递质受体的位置尚不清楚。在这项研究中，我们以细胞自主的方式在成年小鼠大脑中敲除兴奋性或抑制性神经元。出乎意料的是，我们发现，在敲除兴奋性突触前末梢后，兴奋性 AMPA 受体仍然位于突触后密度处。相比之下，抑制性 GABA 受体需要抑制性突触前末梢才能进行突触后定位。与这一发现一致的是，在兴奋性突触前异位表达神经连接蛋白-3α（一种与天然 GABA 受体复合物的假定突触间相互作用蛋白）可以将 GABA 受体募集到被接触的突触后部位。这些结果确立了成熟哺乳动物大脑中兴奋性和抑制性突触后受体维持的不同机制。
