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- Title
SNAP25 differentially contributes to G<sub>i/o</sub>-coupled receptor function at glutamatergic synapses in the nucleus accumbens.
- Authors
Manz, Kevin M.; Zepeda, José C.; Zurawski, Zack; Hamm, Heidi E.; Grueter, Brad A.
- Abstract
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 Gi=o-coupled G-protein-coupled receptors (GPCRs) at glutamatergic synapses onto medium spiny projection neurons (MSNs). Previous work has shown that discrete classes of Gi=o-coupled GPCR mobilize Gbg to inhibit vesicular neurotransmitter release via t-SNARE protein, SNAP25. However, it remains unknown which Gai/o systems in the NAc utilize Gbg-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 (SNAP2513) weaking the Gbg-SNARE interaction, we surveyed a broad cohort of Gi=o-coupled GPCRs with robust inhibitory actions at glutamatergic synapses in the NAc. We find that basal presynaptic glutamate release probability is reduced in SNAP2513 mice. While k 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 GABAB, 5-HT1B=D, and m opioid receptors. These findings demonstrate that presynaptic Gi=o-coupled GPCRs recruit heterogenous effector mechanisms at glutamatergic synapses in the NAc, with a subset requiring SNA25-dependent Gbg signaling.
- Subjects
NUCLEUS accumbens; GLUTAMATE receptors; SYNAPSES; HISTAMINE receptors; OPIOID receptors; TRANSGENIC mice; NEUROPLASTICITY
- Publication
Frontiers in Cellular Neuroscience, 2023, p1
- ISSN
1662-5102
- Publication type
Article
- DOI
10.3389/fncel.2023.1165261