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Excitatory and Inhibitory Receptors Utilize Distinct Post- and Trans-synaptic Mechanisms in Vivo

Overview
Journal Elife
Specialty Biology
Date 2021 Oct 18
PMID 34658339
Citations 5
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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 GABA 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 GABA receptor complex, could recruit GABA 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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References
1.
Uusisaari M, Knopfel T . Functional classification of neurons in the mouse lateral cerebellar nuclei. Cerebellum. 2010; 10(4):637-46. PMC: 3215887. DOI: 10.1007/s12311-010-0240-3. View

2.
Roth A, Hausser M . Compartmental models of rat cerebellar Purkinje cells based on simultaneous somatic and dendritic patch-clamp recordings. J Physiol. 2001; 535(Pt 2):445-72. PMC: 2278793. DOI: 10.1111/j.1469-7793.2001.00445.x. View

3.
Altman J, Anderson W . Experimental reorganization of the cerebellar cortex. I. Morphological effects of elimination of all microneurons with prolonged x-irradiation started at birth. J Comp Neurol. 1972; 146(3):355-406. DOI: 10.1002/cne.901460305. View

4.
Watanabe D, Inokawa H, Hashimoto K, Suzuki N, Kano M, Shigemoto R . Ablation of cerebellar Golgi cells disrupts synaptic integration involving GABA inhibition and NMDA receptor activation in motor coordination. Cell. 1998; 95(1):17-27. DOI: 10.1016/s0092-8674(00)81779-1. View

5.
Gray D, Mahrus S, Wells J . Activation of specific apoptotic caspases with an engineered small-molecule-activated protease. Cell. 2010; 142(4):637-46. PMC: 3689538. DOI: 10.1016/j.cell.2010.07.014. View