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

eLife

Masahiko Watanabe¹  Kotaro Konno¹  Tokiwa Yamasaki²  Megumi Morimoto-Tomita²  Yoav Noam²  Susumu Tomita²  Taisuke Miyazaki³  Matthijs Verhage⁴  Coralie Berthoux⁵  Pablo E Castillo⁵ 

[1] Department of Anatomy, Faculty of Medicine, Hokkaido University, Sapporo, Japan;Department of Cellular and Molecular Physiology, Department of Neuroscience, Yale University School of Medicine, New Haven, United States;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;Department of Clinical Genetics, Center for Neurogenomics and Cognitive Research (CNCR), VU University Amsterdam and VU Medical Center, Amsterdam, Netherlands;Dominick P. Purpura Department of Neuroscience, Albert Einstein College of Medicine, Bronx, United States;

关键词: inhibitory;    excitatory;    receptor;    cell elimination;    in vivo;    postsynaptic;    Mouse;   

DOI  :  10.7554/eLife.59613

来源: eLife Sciences Publications, Ltd

【 摘 要 】

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.

【 授权许可】

CC BY