Excitatory and inhibitory receptors utilize distinct post- and trans-synaptic mechanisms in vivo

• Published in: eLife Vol. 10
• Main Authors: Miyazaki, Taisuke, Morimoto-Tomita, Megumi, Berthoux, Coralie, Konno, Kotaro, Noam, Yoav, Yamasaki, Tokiwa, Verhage, Matthijs, Castillo, Pablo E, Watanabe, Masahiko, Tomita, Susumu
• Format: Journal Article
• Language: English
• Published: England eLife Science Publications, Ltd 18.10.2021; eLife Sciences Publications Ltd; eLife Sciences Publications, Ltd
• Subjects: Ablation; Animals; Brain; cell elimination; Ectopic expression; excitatory; Histology; in vivo; inhibitory; Localization; Mice; Mice, Transgenic; Neuroscience; Neurotransmitter receptors; Post-Synaptic Density - metabolism; postsynaptic; Postsynaptic density; Presynaptic Terminals - metabolism; Proteins; receptor; Receptors, AMPA - metabolism; Receptors, GABA-A - metabolism; Synapses - physiology; Synaptic transmission; Synaptic Transmission - physiology; α-Amino-3-hydroxy-5-methyl-4-isoxazole propionic acid; α-Amino-3-hydroxy-5-methyl-4-isoxazole propionic acid receptors; γ-Aminobutyric acid A receptors; Canada; Japan; mouse; receptor; neuroscience; excitatory; inhibitory; cell elimination; in vivo; postsynaptic
• ISSN: 2050-084X; 2050-084X
• 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.