SNAP25 differentially contributes to G i/o -coupled receptor function at glutamatergic synapses in the nucleus accumbens.

Autor: Manz KM; Department of Anesthesiology, Vanderbilt University Medical Center, Nashville, TN, United States., Zepeda JC; Department of Pharmacology, Vanderbilt University, Nashville, TN, United States., Zurawski Z; Department of Pharmacology, Vanderbilt University, Nashville, TN, United States., Hamm HE; Department of Pharmacology, Vanderbilt University, Nashville, TN, United States., Grueter BA; Department of Anesthesiology, Vanderbilt University Medical Center, Nashville, TN, United States.; Department of Pharmacology, Vanderbilt University, Nashville, TN, United States.; Vanderbilt Brain Institute, Vanderbilt University, Nashville, TN, United States.; Vanderbilt Center for Addiction Research, Vanderbilt University, Nashville, TN, United States.
Jazyk: angličtina
Zdroj: Frontiers in cellular neuroscience [Front Cell Neurosci] 2023 May 02; Vol. 17, pp. 1165261. Date of Electronic Publication: 2023 May 02 (Print Publication: 2023).
DOI: 10.3389/fncel.2023.1165261
Abstrakt: 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.
Competing Interests: The authors declare that the research was conducted in the absence of any commercial or financial relationships that could be construed as a potential conflict of interest.
(Copyright © 2023 Manz, Zepeda, Zurawski, Hamm and Grueter.)
Databáze: MEDLINE
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