| First Author | Manz KM | Year | 2023 |
| Journal | Front Cell Neurosci | Volume | 17 |
| Pages | 1165261 | PubMed ID | 37206665 |
| Mgi Jnum | J:346300 | Mgi Id | MGI:7484891 |
| Doi | 10.3389/fncel.2023.1165261 | Citation | Manz KM, et al. (2023) SNAP25 differentially contributes to G(i/o)-coupled receptor function at glutamatergic synapses in the nucleus accumbens. Front Cell Neurosci 17:1165261 |
| abstractText | 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 Gbetagamma to inhibit vesicular neurotransmitter release via t-SNARE protein, SNAP25. However, it remains unknown which Galphai/o systems in the NAc utilize Gbetagamma-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 (SNAP25Delta3) weaking the Gbetagamma-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 SNAP25Delta3 mice. While kappa 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 mu 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 Gbetagamma signaling. |
