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SNAP25 differentially contributes to G(i/o)-coupled receptor function at glutamatergic synapses in the nucleus accumbens
The nucleus accumbens (NAc) guides reward-related motivated behavior implicated in pathological behavioral states, including addiction and depression. These behaviors depend on the precise neuromodulatory actions of G(i/o)-coupled G-protein-coupled receptors (GPCRs) at glutamatergic synapses onto me...
Autores principales: | , , , , |
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Formato: | Online Artículo Texto |
Lenguaje: | English |
Publicado: |
Frontiers Media S.A.
2023
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Materias: | |
Acceso en línea: | https://www.ncbi.nlm.nih.gov/pmc/articles/PMC10188356/ https://www.ncbi.nlm.nih.gov/pubmed/37206665 http://dx.doi.org/10.3389/fncel.2023.1165261 |
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author | Manz, Kevin M. Zepeda, José C. Zurawski, Zack Hamm, Heidi E. Grueter, Brad A. |
author_facet | Manz, Kevin M. Zepeda, José C. Zurawski, Zack Hamm, Heidi E. Grueter, Brad A. |
author_sort | Manz, Kevin M. |
collection | PubMed |
description | The nucleus accumbens (NAc) guides reward-related motivated behavior implicated in pathological behavioral states, including addiction and depression. These behaviors depend on the precise neuromodulatory actions of G(i/o)-coupled G-protein-coupled receptors (GPCRs) at glutamatergic synapses onto medium spiny projection neurons (MSNs). Previous work has shown that discrete classes of G(i/o)-coupled GPCR mobilize Gβγ to inhibit vesicular neurotransmitter release via t-SNARE protein, SNAP25. However, it remains unknown which Gαi/o systems in the NAc utilize Gβγ-SNARE signaling to dampen glutamatergic transmission. Utilizing patch-clamp electrophysiology and pharmacology in a transgenic mouse line with a C-terminal three-residue deletion of SNAP25 (SNAP25Δ3) weaking the Gβγ-SNARE interaction, we surveyed a broad cohort of G(i/o)-coupled GPCRs with robust inhibitory actions at glutamatergic synapses in the NAc. We find that basal presynaptic glutamate release probability is reduced in SNAP25Δ3 mice. While κ opioid, CB1, adenosine A1, group II metabotropic glutamate receptors, and histamine H3 receptors inhibit glutamatergic transmission onto MSNs independent of SNAP25, we report that SNAP25 contributes significantly to the actions of GABA(B), 5-HT1(B/D), and μ opioid receptors. These findings demonstrate that presynaptic G(i/o)-coupled GPCRs recruit heterogenous effector mechanisms at glutamatergic synapses in the NAc, with a subset requiring SNA25-dependent Gβγ signaling. |
format | Online Article Text |
id | pubmed-10188356 |
institution | National Center for Biotechnology Information |
language | English |
publishDate | 2023 |
publisher | Frontiers Media S.A. |
record_format | MEDLINE/PubMed |
spelling | pubmed-101883562023-05-18 SNAP25 differentially contributes to G(i/o)-coupled receptor function at glutamatergic synapses in the nucleus accumbens Manz, Kevin M. Zepeda, José C. Zurawski, Zack Hamm, Heidi E. Grueter, Brad A. Front Cell Neurosci Neuroscience The nucleus accumbens (NAc) guides reward-related motivated behavior implicated in pathological behavioral states, including addiction and depression. These behaviors depend on the precise neuromodulatory actions of G(i/o)-coupled G-protein-coupled receptors (GPCRs) at glutamatergic synapses onto medium spiny projection neurons (MSNs). Previous work has shown that discrete classes of G(i/o)-coupled GPCR mobilize Gβγ to inhibit vesicular neurotransmitter release via t-SNARE protein, SNAP25. However, it remains unknown which Gαi/o systems in the NAc utilize Gβγ-SNARE signaling to dampen glutamatergic transmission. Utilizing patch-clamp electrophysiology and pharmacology in a transgenic mouse line with a C-terminal three-residue deletion of SNAP25 (SNAP25Δ3) weaking the Gβγ-SNARE interaction, we surveyed a broad cohort of G(i/o)-coupled GPCRs with robust inhibitory actions at glutamatergic synapses in the NAc. We find that basal presynaptic glutamate release probability is reduced in SNAP25Δ3 mice. While κ opioid, CB1, adenosine A1, group II metabotropic glutamate receptors, and histamine H3 receptors inhibit glutamatergic transmission onto MSNs independent of SNAP25, we report that SNAP25 contributes significantly to the actions of GABA(B), 5-HT1(B/D), and μ opioid receptors. These findings demonstrate that presynaptic G(i/o)-coupled GPCRs recruit heterogenous effector mechanisms at glutamatergic synapses in the NAc, with a subset requiring SNA25-dependent Gβγ signaling. Frontiers Media S.A. 2023-05-02 /pmc/articles/PMC10188356/ /pubmed/37206665 http://dx.doi.org/10.3389/fncel.2023.1165261 Text en Copyright © 2023 Manz, Zepeda, Zurawski, Hamm and Grueter. https://creativecommons.org/licenses/by/4.0/This is an open-access article distributed under the terms of the Creative Commons Attribution License (CC BY). The use, distribution or reproduction in other forums is permitted, provided the original author(s) and the copyright owner(s) are credited and that the original publication in this journal is cited, in accordance with accepted academic practice. No use, distribution or reproduction is permitted which does not comply with these terms. |
spellingShingle | Neuroscience Manz, Kevin M. Zepeda, José C. Zurawski, Zack Hamm, Heidi E. Grueter, Brad A. SNAP25 differentially contributes to G(i/o)-coupled receptor function at glutamatergic synapses in the nucleus accumbens |
title | SNAP25 differentially contributes to G(i/o)-coupled receptor function at glutamatergic synapses in the nucleus accumbens |
title_full | SNAP25 differentially contributes to G(i/o)-coupled receptor function at glutamatergic synapses in the nucleus accumbens |
title_fullStr | SNAP25 differentially contributes to G(i/o)-coupled receptor function at glutamatergic synapses in the nucleus accumbens |
title_full_unstemmed | SNAP25 differentially contributes to G(i/o)-coupled receptor function at glutamatergic synapses in the nucleus accumbens |
title_short | SNAP25 differentially contributes to G(i/o)-coupled receptor function at glutamatergic synapses in the nucleus accumbens |
title_sort | snap25 differentially contributes to g(i/o)-coupled receptor function at glutamatergic synapses in the nucleus accumbens |
topic | Neuroscience |
url | https://www.ncbi.nlm.nih.gov/pmc/articles/PMC10188356/ https://www.ncbi.nlm.nih.gov/pubmed/37206665 http://dx.doi.org/10.3389/fncel.2023.1165261 |
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