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

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...

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Autores principales: Taisuke Miyazaki, Megumi Morimoto-Tomita, Coralie Berthoux, Kotaro Konno, Yoav Noam, Tokiwa Yamasaki, Matthijs Verhage, Pablo E Castillo, Masahiko Watanabe, Susumu Tomita
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Publicado: eLife Sciences Publications Ltd 2021
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Acceso en línea:https://doaj.org/article/3b79b81fc19f4bc9932739ee9bebb0d2
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spelling oai:doaj.org-article:3b79b81fc19f4bc9932739ee9bebb0d22021-11-23T13:02:43ZExcitatory and inhibitory receptors utilize distinct post- and trans-synaptic mechanisms in vivo10.7554/eLife.596132050-084Xe59613https://doaj.org/article/3b79b81fc19f4bc9932739ee9bebb0d22021-10-01T00:00:00Zhttps://elifesciences.org/articles/59613https://doaj.org/toc/2050-084XIonotropic 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.Taisuke MiyazakiMegumi Morimoto-TomitaCoralie BerthouxKotaro KonnoYoav NoamTokiwa YamasakiMatthijs VerhagePablo E CastilloMasahiko WatanabeSusumu TomitaeLife Sciences Publications Ltdarticleinhibitoryexcitatoryreceptorcell eliminationin vivopostsynapticMedicineRScienceQBiology (General)QH301-705.5ENeLife, Vol 10 (2021)
institution DOAJ
collection DOAJ
language EN
topic inhibitory
excitatory
receptor
cell elimination
in vivo
postsynaptic
Medicine
R
Science
Q
Biology (General)
QH301-705.5
spellingShingle inhibitory
excitatory
receptor
cell elimination
in vivo
postsynaptic
Medicine
R
Science
Q
Biology (General)
QH301-705.5
Taisuke Miyazaki
Megumi Morimoto-Tomita
Coralie Berthoux
Kotaro Konno
Yoav Noam
Tokiwa Yamasaki
Matthijs Verhage
Pablo E Castillo
Masahiko Watanabe
Susumu Tomita
Excitatory and inhibitory receptors utilize distinct post- and trans-synaptic mechanisms in vivo
description 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.
format article
author Taisuke Miyazaki
Megumi Morimoto-Tomita
Coralie Berthoux
Kotaro Konno
Yoav Noam
Tokiwa Yamasaki
Matthijs Verhage
Pablo E Castillo
Masahiko Watanabe
Susumu Tomita
author_facet Taisuke Miyazaki
Megumi Morimoto-Tomita
Coralie Berthoux
Kotaro Konno
Yoav Noam
Tokiwa Yamasaki
Matthijs Verhage
Pablo E Castillo
Masahiko Watanabe
Susumu Tomita
author_sort Taisuke Miyazaki
title Excitatory and inhibitory receptors utilize distinct post- and trans-synaptic mechanisms in vivo
title_short Excitatory and inhibitory receptors utilize distinct post- and trans-synaptic mechanisms in vivo
title_full Excitatory and inhibitory receptors utilize distinct post- and trans-synaptic mechanisms in vivo
title_fullStr Excitatory and inhibitory receptors utilize distinct post- and trans-synaptic mechanisms in vivo
title_full_unstemmed Excitatory and inhibitory receptors utilize distinct post- and trans-synaptic mechanisms in vivo
title_sort excitatory and inhibitory receptors utilize distinct post- and trans-synaptic mechanisms in vivo
publisher eLife Sciences Publications Ltd
publishDate 2021
url https://doaj.org/article/3b79b81fc19f4bc9932739ee9bebb0d2
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