Excitatory and inhibitory receptors utilize distinct post- and trans-synaptic mechanisms in vivo
Taisuke Miyazaki,
Megumi Morimoto-Tomita,
Coralie Berthoux,
Kotaro Konno,
Yoav Noam,
Tokiwa Yamasaki,
Matthijs Verhage,
Pablo E Castillo,
Masahiko Watanabe,
Susumu Tomita
Affiliations
Taisuke Miyazaki
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; Department of Anatomy, Faculty of Medicine, Hokkaido University, Sapporo, Japan
Megumi Morimoto-Tomita
Department of Cellular and Molecular Physiology, Department of Neuroscience, Yale University School of Medicine, New Haven, United States
Coralie Berthoux
Dominick P. Purpura Department of Neuroscience, Albert Einstein College of Medicine, Bronx, United States
Kotaro Konno
Department of Anatomy, Faculty of Medicine, Hokkaido University, Sapporo, Japan
Yoav Noam
Department of Cellular and Molecular Physiology, Department of Neuroscience, Yale University School of Medicine, New Haven, United States
Tokiwa Yamasaki
Department of Cellular and Molecular Physiology, Department of Neuroscience, Yale University School of Medicine, New Haven, United States
Matthijs Verhage
Department of Clinical Genetics, Center for Neurogenomics and Cognitive Research (CNCR), VU University Amsterdam and VU Medical Center, Amsterdam, Netherlands
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 GABAA 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 GABAA receptor complex, could recruit GABAA receptors to contacted postsynaptic sites. These results establish distinct mechanisms for the maintenance of excitatory and inhibitory postsynaptic receptors in the mature mammalian brain.
