Excitatory and inhibitory receptors utilize distinct post- and trans-synaptic mechanisms in vivo
- Hokkaido University, Japan
- Yale University, United States
- Albert Einstein College of Medicine, United States
- Amsterdam University Medical Center, Netherlands
Abstract
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 3alpha, 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.
Data availability
All data generated or analyzed during this study are included in the manuscript and supporting file. Source Data files showing all raw values for each figure and the original images of uncropped blots for Figure 6B have been provided.
Article and author information
Author details
Funding
NIH Office of the Director (MH115705)
- Susumu Tomita
NIH Office of the Director (MH077939)
- Susumu Tomita
Grant-in-Aid for Scientific Research (MEXT 17K08485)
- Taisuke Miyazaki
Grant-in-Aid for Scientific Research (MEXT 18K06813)
- Taisuke Miyazaki
NIH Office of the Director (F32NS093952)
- Yoav Noam
NIH Office of the Director (NS113600)
- Pablo E Castillo
NIH Office of the Director (MH125772)
- Pablo E Castillo
NIH Office of the Director (MH125772)
- Pablo E Castillo
The funders had no role in study design, data collection and interpretation, or the decision to submit the work for publication.
Ethics
Animal experimentation: All animal handling was in accordance with protocols approved by the Institutional Animal Care and Use Committee (IACUC) of Yale University (Animal Welfare Assurance# A3230-01, Animal protocol number 2021-11029), the Albert Einstein College of Medicine (Animal Welfare Assurance# A3312-011, Animal protocol number 00001043) and Hokkaido University, Japan (Approval number, #19-0111). Animal care and housing were provided by the Yale Animal Resource Center (YARC), in compliance with the Guide for the Care and Use of Laboratory Animals (National Academy Press, Washington, D.C., 1996).
Copyright
© 2021, Miyazaki et al.
This article is distributed under the terms of the Creative Commons Attribution License permitting unrestricted use and redistribution provided that the original author and source are credited.
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Excitatory and inhibitory receptors utilize distinct post- and trans-synaptic mechanisms in vivo
eLife 10:e59613.
https://doi.org/10.7554/eLife.59613
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