TY - JOUR
T1 - Excitatory and inhibitory receptors utilize distinct post-and trans-synaptic mechanisms in vivo
AU - Miyazaki, Taisuke
AU - Morimoto-Tomita, Megumi
AU - Berthoux, Coralie
AU - Konno, Kotaro
AU - Noam, Yoav
AU - Yamasaki, Tokiwa
AU - Verhage, Matthijs
AU - Castillo, Pablo E.
AU - Watanabe, Masahiko
AU - Tomita, Susumu
N1 - Publisher Copyright:
© Miyazaki et al.
PY - 2021/10
Y1 - 2021/10
N2 - Ionotropic neurotransmitter receptors at postsynapses mediate fast synaptic transmis¬sion 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. Consis¬tent 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.
AB - Ionotropic neurotransmitter receptors at postsynapses mediate fast synaptic transmis¬sion 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. Consis¬tent 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.
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U2 - 10.7554/eLife.59613
DO - 10.7554/eLife.59613
M3 - Article
C2 - 34658339
AN - SCOPUS:85118579302
SN - 2050-084X
VL - 10
JO - eLife
JF - eLife
M1 - e59613
ER -