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Title: Postsynaptic receptors regulate presynaptic transmitter stability through transsynaptic bridges
Stable matching of neurotransmitters with their receptors is fundamental to synapse function and reliable communication in neural circuits. Presynaptic neurotransmitters regulate the stabilization of postsynaptic transmitter receptors. Whether postsynaptic receptors regulate stabilization of presynaptic transmitters has received less attention. Here, we show that blockade of endogenous postsynaptic acetylcholine receptors (AChR) at the neuromuscular junction destabilizes the cholinergic phenotype in motor neurons and stabilizes an earlier, developmentally transient glutamatergic phenotype. Further, expression of exogenous postsynaptic gamma-aminobutyric acid type A receptors (GABAAreceptors) in muscle cells stabilizes an earlier, developmentally transient GABAergic motor neuron phenotype. Both AChR and GABAAreceptors are linked to presynaptic neurons through transsynaptic bridges. Knockdown of specific components of these transsynaptic bridges prevents stabilization of the cholinergic or GABAergic phenotypes. Bidirectional communication can enforce a match between transmitter and receptor and ensure the fidelity of synaptic transmission. Our findings suggest a potential role of dysfunctional transmitter receptors in neurological disorders that involve the loss of the presynaptic transmitter.  more » « less
Award ID(s):
2051555
PAR ID:
10501693
Author(s) / Creator(s):
; ; ; ; ; ; ; ; ; ; ;
Corporate Creator(s):
Editor(s):
NA
Publisher / Repository:
PNAS
Date Published:
Journal Name:
Proceedings of the National Academy of Sciences
Edition / Version:
1.0
Volume:
121
Issue:
15
ISSN:
0027-8424
Page Range / eLocation ID:
e2318041121
Subject(s) / Keyword(s):
Transmitter receptors, neurotransmitters, transmitter stability, transmitter selection, transsynaptic bridges
Format(s):
Medium: X Size: 16.2MB Other: MS Word
Size(s):
16.2MB
Sponsoring Org:
National Science Foundation
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