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.
Bibliographical noteFunding Information:
NIH Office of the DirectorMH115705 Susumu Tomita NIH Office of the DirectorMH077939 Susumu Tomita Ministry of Education, Culture, Sports, Science and Technology Grant-in-Aid for Scientific Research 17K08485 Taisuke Miyazaki Ministry of Education, Culture, Sports, Science and Technology Grant-in-Aid for Scientific Research 18K06813 Taisuke Miyazaki NIH Office of the DirectorF32NS093952 Yoav Noam NIH Office of the DirectorNS113600 Pablo E Castillo NIH Office of the DirectorMH125772 Pablo E Castillo.
© Miyazaki et al.