Affinage

SLC17A6

Vesicular glutamate transporter 2 · UniProt Q9P2U8

Length
582 aa
Mass
64.4 kDa
Annotated
2026-06-10
100 papers in source corpus 28 papers cited in narrative 28 extracted findings
Cross-family judge vs UniProt: Affinage preferred faithfulness: 7/7 claims corpus-supported (100%)

Mechanistic narrative

Synthesis pass · prose summary of the discoveries below

SLC17A6 (VGLUT2) is a proton-gradient-driven vesicular glutamate transporter that loads L-glutamate into synaptic vesicles and synaptic-like microvesicles, and its expression alone is sufficient to confer glutamatergic transmission on otherwise non-glutamatergic neurons (PMID:11698620, PMID:11551935). Heterologous reconstitution established that transport occurs at the expense of a vacuolar H+-pump-generated electrochemical proton gradient and operates as an H+/L-glutamate antiporter, with an additional plasma-membrane efflux mode (PMID:11551935, PMID:18080752). VGLUT2 marks a synaptic vesicle population largely distinct from the VGLUT1 pool in mature neurons, though the two transporters can co-reside on the same vesicles early in development (PMID:11698620, PMID:16942593). Synaptic targeting and endocytic recycling depend on a C-terminal dileucine-like motif that binds the clathrin adaptors AP-1, AP-2, and AP-3; mutation of this motif abolishes synaptic localization and endocytosis (PMID:29123471). In midbrain dopamine neurons VGLUT2 enables glutamate co-release that shapes mesoaccumbal synaptic plasticity and psychostimulant and reward behaviors, regulates dopamine release and clearance, and is a determinant of dopamine-neuron survival, axonal outgrowth, and post-lesional reinnervation (PMID:20018672, PMID:21880920, PMID:29337309, PMID:30210305, PMID:32928885). In TRPV1/Nav1.8-lineage primary afferents and spinal dorsal horn interneurons, VGLUT2 is essential for thermal nociception and heat hyperalgesia and for suppression of itch (PMID:21040852, PMID:21135246, PMID:28157737, PMID:30203849). VGLUT2 expression is dynamically regulated by neuronal activity through CaMK/ERK1/2 signaling (PMID:20212045), by Wnt1/β-catenin signaling after nerve injury (PMID:31785260), and epigenetically via DNA methylation, H3K4me3, and miR-467b-5p at its locus (PMID:26421062).

Mechanistic history

Synthesis pass · year-by-year structured walk · 12 steps
  1. 2001 High

    Established that SLC17A6 is itself a functional vesicular glutamate transporter and not merely a marker, answering whether the protein could account for glutamate loading and glutamatergic transmission.

    Evidence Heterologous expression in BON and COS7 cells with ATP- and proton-gradient-dependent uptake assays, plus overexpression in GABAergic neurons driving AMPA-receptor currents, with EM/fractionation localizing it to synaptic-like microvesicles

    PMID:11551935 PMID:11698620

    Open questions at the time
    • Transport stoichiometry and ion coupling not fully quantified
    • No structural model of the transporter
  2. 2003 Medium

    Defined how VGLUT2 partitions relative to VGLUT1, showing they mark non-overlapping vesicle pools in mature neurons but can co-reside on the same vesicles developmentally.

    Evidence Subcellular fractionation, synaptic-vesicle immunoisolation, and confocal co-localization in hippocampal preparations

    PMID:11698620 PMID:16942593

    Open questions at the time
    • Mechanism of developmental vesicle sorting between VGLUT1 and VGLUT2 not defined
    • Single-lab fractionation evidence
  3. 2007 Medium

    Resolved the substrate specificity and transport modes, showing selective L-glutamate (not aspartate) handling consistent with H+/L-glutamate antiport plus an efflux mode.

    Evidence Xenopus oocyte radiolabeled influx/efflux assays with pharmacological inhibition (rose bengal, trypan blue)

    PMID:18080752

    Open questions at the time
    • Single expression system, single lab
    • Physiological relevance of the plasma-membrane efflux mode unestablished
  4. 2009 High

    Demonstrated in vivo that VGLUT2-mediated glutamate co-release from dopamine neurons is required for psychostimulant-driven behavioral activation, moving the transporter from biochemistry into circuit function.

    Evidence DAT-Cre/Vglut2-flox conditional knockout with amperometry and amphetamine locomotor behavior

    PMID:20018672

    Open questions at the time
    • Did not isolate which downstream synapses mediate the behavior
    • Developmental versus acute contribution not separated
  5. 2010 High

    Identified an essential role for VGLUT2 in primary afferent and spinal sensory circuits, establishing it as the dedicated mediator of heat nociception and heat hyperalgesia and a suppressor of itch.

    Evidence TRPV1-Cre and Nav1.8-Cre conditional knockouts with spinal in vivo electrophysiology, behavioral nociception/itch assays, injury models, and GRPR epistasis

    PMID:21040852 PMID:21135246

    Open questions at the time
    • Why mechanical hypersensitivity is VGLUT2-independent unexplained
    • Molecular basis of the itch-suppression circuit incomplete
  6. 2010 Medium

    Showed that VGLUT2 expression is activity-regulated, linking glutamatergic drive to a defined Ca2+/CaMK/ERK transcriptional cascade.

    Evidence Pharmacological pathway dissection (iGluR, L-type Ca2+ channels, calmodulin, CaMK, ERK1/2) with transcription blockade and immunostaining in neocortical culture

    PMID:20212045

    Open questions at the time
    • Transcription factors acting at the promoter not identified
    • In vivo relevance not tested
  7. 2017 High

    Defined the trafficking determinant, mapping synaptic targeting and recycling to a C-terminal dileucine-like motif that engages specific clathrin adaptors.

    Evidence pHluorin live imaging, motif mutagenesis, co-immunoprecipitation with AP-1/2/3, and adaptor shRNA knockdown in neurons

    PMID:29123471

    Open questions at the time
    • Structural basis of adaptor selectivity unknown
    • Single lab; no reciprocal in vivo validation of adaptor requirement
  8. 2017 High

    Extended the sensory role to spinal interneurons, showing VGLUT2 underlies glutamatergic itch transmission in GRPR neurons and broadly drives dorsal-horn nociceptive output.

    Evidence Grpr-Cre and VGluT2-Cre conditional/chemogenetic manipulations with patch-clamp, calcium imaging, and behavioral pain/itch assays

    PMID:28157737 PMID:30203849

    Open questions at the time
    • Connectivity between afferent and interneuronal VGLUT2 circuits not fully mapped
  9. 2018 High

    Established VGLUT2 expression level as a bidirectional determinant of dopamine-neuron vulnerability and a direct modulator of mesoaccumbal plasticity.

    Evidence Viral overexpression and conditional/inducible deletion in SNc/VTA DA neurons with neurotoxin challenge, optogenetics-coupled patch-clamp, and AMPA/NMDA ratio measurements

    PMID:29337309 PMID:30210305

    Open questions at the time
    • Molecular mechanism linking VGLUT2 level to survival not defined
    • Whether glutamate co-release or transporter expression per se drives protection unresolved
  10. 2020 High

    Showed a developmental and regenerative role, with VGLUT2 promoting dopaminergic axonal outgrowth and striatal reinnervation after lesion.

    Evidence Intersectional fate-mapping, embryonic immunofluorescence, conditional knockout, and 6-OHDA lesion with axon density quantification

    PMID:32928885

    Open questions at the time
    • Cell-autonomous signaling that couples VGLUT2 to axon growth not identified
  11. 2020 High

    Broadened the regulatory and circuit repertoire, implicating VGLUT2 neurons in opioid and cannabinoid reward/aversion and in autonomic/thermoregulatory control.

    Evidence Cell-type-specific receptor (MOR, CB1) deletions in VgluT2-Cre mice and chemogenetic VNC manipulations with behavioral, microdialysis, and physiological readouts

    PMID:28951549 PMID:32385401 PMID:32686251 PMID:33444596

    Open questions at the time
    • Whether effects require glutamate transport activity versus neuronal identity not always dissociated
  12. 2021 Medium

    Defined upstream regulatory inputs controlling VGLUT2 levels in disease and injury contexts (Wnt1/β-catenin, epigenetic and miRNA control, neuroprotective upregulation).

    Evidence Intrathecal shRNA epistasis with Wnt pharmacology, ChIP/bisulfite/3'UTR-reporter analyses, and correlational neuroanatomy in rotenone and ALS models

    PMID:19770042 PMID:26421062 PMID:31785260 PMID:33893220

    Open questions at the time
    • Causal manipulation of VGLUT2 absent in the rotenone study
    • Integration of activity-, Wnt-, and epigenetic regulation into a single regulatory model lacking

Open questions

Synthesis pass · forward-looking unresolved questions
  • How VGLUT2 transporter structure underlies ion coupling, substrate selectivity, and the molecular logic by which the dileucine motif selects among AP adaptors remains unresolved.
  • No structural model of the transporter
  • Adaptor-selectivity determinants undefined
  • No human Mendelian disease link established in this corpus

Mechanism profile

Synthesis pass · controlled-vocabulary classification · explore literature graph →
Molecular activity
GO:0005215 transporter activity 3 GO:0005829 cytosol 1
Localization
GO:0031410 cytoplasmic vesicle 4 GO:0005886 plasma membrane 1
Pathway
R-HSA-112316 Neuronal System 4 R-HSA-382551 Transport of small molecules 3 R-HSA-5653656 Vesicle-mediated transport 1
Partners
AP1AP2AP3

Evidence

Reading pass · 28 per-paper findings extracted from the source corpus
Year Finding Method Journal Conf PMIDs
2001 DNPI (SLC17A6/VGLUT2) functions as a vesicular glutamate transporter: when expressed in BON cells, membrane fractions displayed ATP-dependent, FCCP-sensitive glutamate uptake; overexpression in cultured GABAergic neurons caused release of glutamate activating AMPA receptors, demonstrating that VGLUT2 expression alone is sufficient to confer glutamatergic transmission. Heterologous expression in BON cells (ATP-dependent uptake assay), overexpression in autaptic GABAergic neurons with electrophysiology (bicuculline-insensitive, NBQX-sensitive postsynaptic currents) The Journal of Neuroscience High 11698620
2001 DNPI/VGLUT2, when expressed in COS7 cells, transports L-glutamate at the expense of an electrochemical proton gradient established by the vacuolar proton pump, confirming it as a bona fide vesicular glutamate transporter. It is present on synaptic-like microvesicles (SLMVs) in pinealocytes and pancreatic alpha cells and is responsible for vesicular glutamate storage in these endocrine cells. Heterologous expression in COS7 cells (proton-gradient-dependent glutamate uptake assay), immunoelectron microscopy and subcellular fractionation showing co-fractionation with SLMVs The Journal of Biological Chemistry High 11551935
2003 VGLUT2 is highly enriched in synaptic vesicles and resides on a vesicle population distinct from those containing VGAT or VGLUT1, showing that VGLUT1 and VGLUT2 mark non-overlapping vesicle populations. Subcellular fractionation, immunoisolation of synaptic vesicles, co-immunolocalization The Journal of Neuroscience Medium 11698620
2007 VGLUT2 expressed in Xenopus oocytes mediates two independent transport modes: (1) uptake of L-glutamate (but not D-aspartate) into intracellular organelles in digitonin-permeabilized oocytes, and (2) efflux of L-glutamate (but not L-aspartate) from intact oocytes, consistent with H+/L-glutamate antiport and a potential plasma-membrane leakage mode. Transport was blocked by rose bengal and trypan blue. Heterologous expression in Xenopus oocytes, radiolabeled glutamate influx and efflux assays, pharmacological inhibition Neurochemical Research Medium 18080752
2009 Conditional deletion of VGLUT2 in dopamine neurons (DAT-Cre/Vglut2-lox mice) does not affect basal motor function but greatly blunts locomotor response to amphetamine and alters risk-taking behavior, demonstrating that VGLUT2 expression in DA neurons is required for psychostimulant-induced behavioral activation. Conditional knockout (DAT-Cre/Vglut2-flox), in vivo amperometry, behavioral assays (open-field, amphetamine locomotion) Proceedings of the National Academy of Sciences of the United States of America High 20018672
2010 Conditional deletion of VGLUT2 in TRPV1-lineage primary afferents causes dramatic increase in itch behavior and reduced responsiveness to thermal pain, establishing that VGLUT2 in these nociceptors is required for thermal nociception and suppression of itch. Conditional knockout (TRPV1-Cre/Vglut2-flox), behavioral assays (thermal pain, mechanical pain, itch), pharmacological rescue with antihistamines and GRPR-KO epistasis Neuron High 21040852
2010 Conditional knockout of Slc17a6 (VGLUT2) from the majority of DRG nociceptors profoundly decreases VGLUT2 protein, reduces lamina I spinal cord neuron firing to noxious heat and mechanical stimuli, and impairs acute noxious heat, mechanical, and capsaicin responses. Heat hyperalgesia after tissue or nerve injury is lost, but mechanical hypersensitivity is intact, revealing a VGLUT2-dependent mechanism specifically for heat pain. Conditional knockout (Nav1.8-Cre/Vglut2-flox), in vivo electrophysiology of spinal neurons, behavioral nociceptive assays, nerve injury models Proceedings of the National Academy of Sciences of the United States of America High 21135246
2010 Activity-dependent induction of VGLUT2 mRNA and synaptic protein in mature neocortical neurons is triggered by prolonged increase in glutamatergic activity and requires signaling through ionotropic glutamate receptors, L-type voltage-gated Ca2+ channels, calmodulin, CaMK, and ERK1/2. Induced VGLUT2 protein appears on synaptic vesicles at excitatory synapses onto GABAergic interneurons. Pharmacological blockade of activity, calcium signaling inhibitors, actinomycin D transcription blockade, Western blot, immunofluorescence in neocortical culture The Journal of Biological Chemistry Medium 20212045
2011 Conditional deletion of Vglut2 in DA neurons (DAT-Cre/Vglut2-flox) enhances operant self-administration of sucrose and intravenous cocaine and increases cocaine seeking maintained by drug-paired cues by 76%; it also reduces potassium-evoked DA release in striatum and increases DA receptor binding, indicating that VGLUT2-mediated glutamate co-release from DA neurons regulates reward-dependent plasticity. Conditional knockout (DAT-Cre/Vglut2-flox), operant self-administration, in vivo DA chronoamperometry, DA receptor autoradiography, immediate-early gene in situ hybridization The Journal of Neuroscience High 21880920
2012 Conditional deletion of VGLUT2 throughout development using Emx1-Cre reduces evoked glutamate transmission, release probability, and LTD at hippocampal CA3-CA1 synapses during postnatal days 11-14. In adults, it causes reduced dendritic arbor and spine density of CA1 pyramidal neurons, impaired LTP, and spatial learning/memory deficits that are partially rescued by enhancing NMDA receptor-mediated transmission with D-serine. Conditional knockout (Emx1-Cre/Vglut2-flox), whole-cell patch-clamp electrophysiology, Golgi staining for dendritic morphology, behavioral spatial memory tests, pharmacological NMDAR enhancement The Journal of Neuroscience High 23136427
2014 Conditional reduction of Vglut2 in a Pitx2-co-expressing subpopulation of subthalamic nucleus neurons reduces glutamatergic transmission to substantia nigra pars reticulata and entopeduncular nucleus, causes hyperlocomotion and decreased movement initiation latency, and reduces dopamine transporter binding with slower dopamine clearance in vivo, demonstrating that VGLUT2-expressing STN neurons regulate both motor output and dopaminergic transmission. Conditional knockout (Pitx2-Cre subpopulation targeting/Vglut2-flox), electrophysiology in STN targets, behavioral locomotion assays, DAT binding assay, in vivo voltammetry Proceedings of the National Academy of Sciences of the United States of America High 24821804
2017 VGLUT2 trafficking to synaptic vesicles depends on a C-terminal dileucine-like motif; disruption of this motif abolishes synaptic targeting and essentially eliminates endocytosis. VGLUT2 interacts biochemically with clathrin adaptor proteins AP-1, AP-2, and AP-3 at this motif. VGLUT2 recycling is slower than VGLUT1 and relies on AP-1 and AP-3 (not just AP-2), as shown by shRNA knockdown of individual adaptors. pHluorin-reporter live imaging, site-directed mutagenesis of dileucine-like motif, co-immunoprecipitation with AP-1/2/3, shRNA knockdown of adaptors in hippocampal and thalamic neurons Frontiers in Cellular Neuroscience High 29123471
2018 Overexpression of VGLUT2 specifically in murine SNc DA neurons causes neuronal loss and Parkinsonian behaviors; conditional deletion of VGLUT2 from DA neurons increases their susceptibility to Parkinsonian neurotoxins. These opposing effects establish VGLUT2 expression level as a crucial determinant of DA neuron survival and selective vulnerability. Viral-vector VGLUT2 overexpression in SNc, conditional knockout (DA neuron-specific), neurotoxin challenge, behavioral Parkinsonism assays, histological DA neuron counts The Journal of Clinical Investigation High 29337309
2018 Tamoxifen-inducible conditional deletion of Vglut2 in mature DA neurons reduces glutamatergic transmission from DA axons to nucleus accumbens medium spiny neurons (optogenetics-coupled patch clamp), and increases the baseline AMPA/NMDA ratio in DRD1-expressing MSNs, occluding subsequent cocaine-induced synaptic potentiation. This identifies VGLUT2-mediated glutamate co-release as a direct modulator of synaptic plasticity in the mesoaccumbal circuit. Tamoxifen-inducible Cre-LoxP (adult-stage deletion), optogenetics-coupled patch-clamp in nucleus accumbens, AMPA/NMDA ratio measurements Frontiers in Neural Circuits High 30210305
2017 Spinal cord interneurons expressing GRPR use VGLUT2-mediated signaling to transmit itch: conditional deletion of Vglut2 in Grpr-Cre cells (Vglut2-lox;Grpr-Cre mice) reduces spontaneous itch and attenuated responses to both histaminergic and nonhistaminergic pruritogens. Gastrin-releasing peptide induces spike responses and natriuretic polypeptide B induces calcium influx in this population. Conditional knockout (Grpr-Cre/Vglut2-lox), behavioral itch assays, patch-clamp electrophysiology, calcium imaging Pain High 28157737
2018 VGluT2-expressing excitatory neurons in spinal dorsal horn lamina II are required for nociceptive transmission: chemogenetic activation of hM3D-DREADD in VGluT2-Cre neurons increases neuronal firing and synaptic glutamate release, whereas inhibitory KORD activation reduces them. Chemogenetic silencing reverses inflammatory and neuropathic pain hypersensitivity. Chemogenetic (DREADD) activation and inhibition via AAV-Cre-dependent vectors in VGluT2-Cre mice, patch-clamp recording of dorsal horn neurons, behavioral pain assays Journal of Neurochemistry High 30203849
2004 Dopamine neurons in postnatal rat mesencephalic cultures express VGLUT2 (but not VGLUT1 or VGLUT3), as confirmed by single-cell RT-PCR, providing the molecular basis for glutamate co-release by DA neurons. Only a proportion of terminals from individual DA neurons are VGLUT2-positive, indicating heterogeneous axonal phenotype. Immunocytochemistry, single-cell RT-PCR in isolated DA neurons Journal of Neurochemistry Medium 15009640
2020 VGluT2 expression in DA neurons promotes axonal outgrowth and striatal reinnervation after neurotoxin lesion: >98% of DA neurons have a VGluT2+ developmental lineage (intersectional fate-mapping), VGluT2 is detected in developing DA axons at E11.5, and conditional removal of VGluT2 from DA neurons reduces striatal connections 7 weeks post-lesion. Intersectional genetic lineage mapping, embryonic immunofluorescence, conditional knockout (DA-Cre/Vglut2-flox), 6-OHDA lesion model, axon density quantification The Journal of Neuroscience High 32928885
2021 In the rotenone rat model of Parkinson's disease, VGLUT2-expressing DA neurons are more resilient to neurodegeneration than VGLUT2-negative neurons; rotenone also increases the density of VGLUT2-detectable DA neurons in VTA and SNc, suggesting upregulation of VGLUT2 as part of a neuroprotective response. Rotenone rat model, immunofluorescence double-labeling for TH/VGLUT2, stereological neuron counting, analysis of striatal terminal density The Journal of Neuroscience Medium 33893220
2009 Genetic reduction of VGLUT2 protein in SOD1(G93A) ALS mice rescues motor neurons in the lumbar spinal cord and brainstem and preserves neuromuscular junctions in tibialis anterior, without altering disease onset or lifespan, establishing that VGLUT2-mediated glutamate release at motor neuron synapses contributes to excitotoxic degeneration in ALS. Genetic reduction of Vglut2 on SOD1(G93A) background, histological motor neuron counts, NMJ morphology, survival analysis Neurobiology of Disease Medium 19770042
2003 VGLUT2 co-localizes with VGLUT1 in the same synaptic vesicles in young hippocampal mossy fibers, demonstrating that co-expressing neurons do not sort the two transporters into separate vesicle pools at early developmental stages. Immunofluorescence, confocal microscopy, and immunoisolation of synaptic vesicles showing co-fractionation of VGLUT1 and VGLUT2 Journal of Neurochemistry Medium 16942593
2005 VGLUT2 expression in hypothalamic-neurohypophysial vasopressin (and some oxytocin) magnocellular neurons is up-regulated by osmotic challenge (water deprivation or salt loading), and VGLUT2 immunoreactivity in vasopressin terminals of the neurohypophysis is reduced after stimulation, suggesting regulated vesicular glutamate co-release in response to osmotic stress. In situ hybridization for VGLUT2 mRNA, immunohistochemistry for VGLUT2 protein, double-label with vasopressin/oxytocin markers, osmotic challenge paradigms The European Journal of Neuroscience Medium 16101749 16842872
2015 Prenatal ethanol exposure upregulates Slc17a6 (VGLUT2) mRNA in male offspring hippocampus correlated with decreased DNA methylation and enrichment of active histone H3K4me3 at the Slc17a6 promoter. Despite mRNA upregulation, hippocampal VGLUT2 protein is decreased, due in part to miR-467b-5p, which was confirmed to interact with the 3'UTR of Slc17a6 in a reporter assay. ChIP for H3K4me3, bisulfite sequencing for DNA methylation, microRNA profiling, luciferase 3'UTR reporter assay, Western blot and qRT-PCR Epigenetics & Chromatin Medium 26421062
2020 Deletion of VGLUT2 from midbrain DA neurons attenuates both dopamine and glutamate release in the nucleus accumbens induced by methamphetamine (measured by microdialysis) and reduces METH-induced locomotion, demonstrating that VGLUT2-mediated glutamate co-release from DA neurons contributes to METH-induced NAc glutamate increases. Conditional knockout (DAT-Cre/Vglut2-flox), in vivo brain microdialysis for DA and glutamate, locomotor behavioral assay Pharmacology, Biochemistry, and Behavior Medium 33444596
2020 VGLUT2-expressing neurons in the vestibular nuclear complex mediate hypergravity (2g)-induced hypothermia via sympathoinhibition: bilateral chemogenetic activation of VNC VGLUT2 neurons alone induces hypothermia, and their conditional deletion suppresses 2g-induced hypothermia, whereas VGAT-expressing VNC neuron manipulation does not affect this phenotype. Conditional deletion of VGLUT2 in VNC neurons, DREADD-based chemogenetic activation, plasma catecholamine measurement, brown adipose tissue thermography, behavioral assay under 2g load Communications Biology High 32385401
2019 Wnt1/β-catenin signaling upregulates spinal VGLUT2 protein after nerve injury. Blocking Wnt1 with a targeting antibody or inhibiting β-catenin with XAV939 reduces VGLUT2 levels and attenuates mechanical allodynia; pretreatment with VGLUT2 shRNA abolishes Wnt-agonist-induced allodynia, placing VGLUT2 downstream of Wnt1/β-catenin signaling in neuropathic pain. Intrathecal shRNA knockdown, Wnt agonist/antagonist pharmacology, Western blot for VGLUT2 and β-catenin pathway proteins, behavioral pain assays Neuropharmacology Medium 31785260
2017 CB1 receptors on VgluT2-expressing glutamatergic neurons in the VTA mediate Δ9-THC-induced conditioned place aversion and reduction in optical intracranial self-stimulation: selective deletion of CB1Rs in VgluT2-expressing neurons (VgluT2-CB1-/-) abolishes THC-induced aversion but not reward, establishing that CB1R activation on glutamatergic (VGLUT2+) VTA neurons produces aversive effects. Cre-loxP selective CB1R deletion in VgluT2-Cre mice, optogenetic activation of VTA glutamatergic neurons, conditioned place aversion, intracranial self-stimulation, DA receptor antagonist pharmacology Scientific Reports High 28951549
2020 Mu opioid receptors (MOR) on vGluT2-expressing neurons directly mediate inhibition of glutamate transmission: MORflox-vGluT2cre mice (lacking MORs selectively on vGluT2 neurons) fail to acquire conditioned place preference for low-dose oxycodone and display conditioned place aversion at higher dose; they also fail to show oxycodone-induced locomotion and consume less oxycodone, demonstrating that MOR-mediated regulation of VGLUT2-neuron glutamate release is critical for opioid reward. Conditional knockout of MOR in vGluT2-Cre neurons, conditioned place preference/aversion, oral consumption assay, locomotor assay Addiction Biology Medium 32686251

Source papers

Stage 0 corpus · 100 papers · ranked by NIH iCite citations
Year Title Journal Citations PMID
2000 Regional expression of a gene encoding a neuron-specific Na(+)-dependent inorganic phosphate cotransporter (DNPI) in the rat forebrain. Brain research. Molecular brain research 671 11072093
2003 The expression of vesicular glutamate transporters VGLUT1 and VGLUT2 in neurochemically defined axonal populations in the rat spinal cord with emphasis on the dorsal horn. The European journal of neuroscience 363 12534965
2001 Identification of differentiation-associated brain-specific phosphate transporter as a second vesicular glutamate transporter (VGLUT2). The Journal of neuroscience : the official journal of the Society for Neuroscience 298 11698620
2003 Hypothalamic orexin (hypocretin) neurons express vesicular glutamate transporters VGLUT1 or VGLUT2. The Journal of comparative neurology 209 12975818
2002 Vesicular glutamate transporter DNPI/VGLUT2 mRNA is present in C1 and several other groups of brainstem catecholaminergic neurons. The Journal of comparative neurology 196 11840474
2010 VGLUT2-dependent sensory neurons in the TRPV1 population regulate pain and itch. Neuron 168 21040852
2002 Vesicular glutamate transporter DNPI/VGLUT2 is expressed by both C1 adrenergic and nonaminergic presympathetic vasomotor neurons of the rat medulla. The Journal of comparative neurology 159 11840475
2007 Loss of VGLUT1 and VGLUT2 in the prefrontal cortex is correlated with cognitive decline in Alzheimer disease. Neurobiology of aging 137 17531353
2004 Dopamine neurons in culture express VGLUT2 explaining their capacity to release glutamate at synapses in addition to dopamine. Journal of neurochemistry 132 15009640
2005 VGluT2 immunochemistry identifies thalamocortical terminals in layer 4 of adult and developing visual cortex. The Journal of comparative neurology 113 15770654
2009 VGLUT2 in dopamine neurons is required for psychostimulant-induced behavioral activation. Proceedings of the National Academy of Sciences of the United States of America 110 20018672
2006 Synaptic and vesicular co-localization of the glutamate transporters VGLUT1 and VGLUT2 in the mouse hippocampus. Journal of neurochemistry 108 16942593
2003 Expression of vesicular glutamate transporters, VGluT1 and VGluT2, in axon terminals of nociceptive primary afferent fibers in the superficial layers of the medullary and spinal dorsal horns of the rat. The Journal of comparative neurology 102 12541308
2006 Altered expression of vesicular glutamate transporters VGLUT1 and VGLUT2 in Parkinson disease. Neurobiology of aging 101 16563567
2010 VGLUT2 expression in primary afferent neurons is essential for normal acute pain and injury-induced heat hypersensitivity. Proceedings of the National Academy of Sciences of the United States of America 100 21135246
2001 Differentiation-associated Na+-dependent inorganic phosphate cotransporter (DNPI) is a vesicular glutamate transporter in endocrine glutamatergic systems. The Journal of biological chemistry 96 11551935
2002 Expression of inorganic phosphate/vesicular glutamate transporters (BNPI/VGLUT1 and DNPI/VGLUT2) in the cerebellum and precerebellar nuclei of the rat. Brain research. Molecular brain research 93 12414120
2018 Role for VGLUT2 in selective vulnerability of midbrain dopamine neurons. The Journal of clinical investigation 84 29337309
2014 vglut2 and gad expression reveal distinct patterns of dual GABAergic versus glutamatergic cotransmitter phenotypes of dopaminergic and noradrenergic neurons in the zebrafish brain. The Journal of comparative neurology 79 24374659
2011 Enhanced sucrose and cocaine self-administration and cue-induced drug seeking after loss of VGLUT2 in midbrain dopamine neurons in mice. The Journal of neuroscience : the official journal of the Society for Neuroscience 78 21880920
2004 Differential co-localisation of the P2X7 receptor subunit with vesicular glutamate transporters VGLUT1 and VGLUT2 in rat CNS. Neuroscience 75 14706788
2004 Expression of vesicular glutamate transporters, VGLUT1 and VGLUT2, in cholinergic spinal motoneurons. The European journal of neuroscience 72 15379996
2015 Prenatal ethanol exposure alters adult hippocampal VGLUT2 expression with concomitant changes in promoter DNA methylation, H3K4 trimethylation and miR-467b-5p levels. Epigenetics & chromatin 63 26421062
2003 Vesicular glutamate transporters, VGluT1 and VGluT2, in the trigeminal ganglion neurons of the rat, with special reference to coexpression. The Journal of comparative neurology 62 12815758
2011 Parasagittal compartmentation of cerebellar mossy fibers as revealed by the patterned expression of vesicular glutamate transporters VGLUT1 and VGLUT2. Brain structure & function 60 21814870
2017 CB1 Receptor Activation on VgluT2-Expressing Glutamatergic Neurons Underlies Δ9-Tetrahydrocannabinol (Δ9-THC)-Induced Aversive Effects in Mice. Scientific reports 58 28951549
2012 Neurodevelopmental role for VGLUT2 in pyramidal neuron plasticity, dendritic refinement, and in spatial learning. The Journal of neuroscience : the official journal of the Society for Neuroscience 58 23136427
2010 Origins of Glutamatergic Terminals in the Inferior Colliculus Identified by Retrograde Transport and Expression of VGLUT1 and VGLUT2 Genes. Frontiers in neuroanatomy 58 21048892
2007 VGLUT1 and VGLUT2 innervation in autonomic regions of intact and transected rat spinal cord. The Journal of comparative neurology 56 17570127
2019 Audiogenic Seizures in the Fmr1 Knock-Out Mouse Are Induced by Fmr1 Deletion in Subcortical, VGlut2-Expressing Excitatory Neurons and Require Deletion in the Inferior Colliculus. The Journal of neuroscience : the official journal of the Society for Neuroscience 53 31666356
2004 Vesicular glutamate transporters in the lateral geniculate nucleus: expression of VGLUT2 by retinal terminals. Brain research 53 14697503
2010 VGLUT1 and VGLUT2 mRNA expression in the primate auditory pathway. Hearing research 49 21111036
2003 Co-expression of vesicular glutamate transporters (VGLUT1 and VGLUT2) and their association with synaptic-like microvesicles in rat pinealocytes. Journal of neurochemistry 48 12559000
2017 The role of miR-190a-5p contributes to diabetic neuropathic pain via targeting SLC17A6. Journal of pain research 47 29042815
2006 Expression of the vesicular glutamate transporter vGluT2 in a subset of cones of the mouse retina. The Journal of comparative neurology 46 16572432
2022 Parkinson's disease-associated, sex-specific changes in DNA methylation at PARK7 (DJ-1), SLC17A6 (VGLUT2), PTPRN2 (IA-2β), and NR4A2 (NURR1) in cortical neurons. NPJ Parkinson's disease 45 36151217
2017 Spinal cord interneurons expressing the gastrin-releasing peptide receptor convey itch through VGLUT2-mediated signaling. Pain 45 28157737
2008 VGluT2 expression in painful Achilles and patellar tendinosis: evidence of local glutamate release by tenocytes. Journal of orthopaedic research : official publication of the Orthopaedic Research Society 41 18050306
2008 Large projection neurons in lamina I of the rat spinal cord that lack the neurokinin 1 receptor are densely innervated by VGLUT2-containing axons and possess GluR4-containing AMPA receptors. The Journal of neuroscience : the official journal of the Society for Neuroscience 41 19052206
2003 Vesicular glutamate transporters VGLUT1 and VGLUT2 define two subsets of unipolar brush cells in organotypic cultures of mouse vestibulocerebellum. Neuroscience 41 14614902
2013 Confocal laser scanning microscopy and ultrastructural study of VGLUT2 thalamic input to striatal projection neurons in rats. The Journal of comparative neurology 40 23047588
2007 Vesicular glutamate transporters VGLUT1 and VGLUT2 in the developing mouse barrel cortex. International journal of developmental neuroscience : the official journal of the International Society for Developmental Neuroscience 40 17289331
2014 Limiting glutamate transmission in a Vglut2-expressing subpopulation of the subthalamic nucleus is sufficient to cause hyperlocomotion. Proceedings of the National Academy of Sciences of the United States of America 38 24821804
2018 Regulating nociceptive transmission by VGluT2-expressing spinal dorsal horn neurons. Journal of neurochemistry 37 30203849
2010 Excitation-transcription coupling via calcium/calmodulin-dependent protein kinase/ERK1/2 signaling mediates the coordinate induction of VGLUT2 and Narp triggered by a prolonged increase in glutamatergic synaptic activity. The Journal of biological chemistry 37 20212045
2009 Regional and laminar distribution of the vesicular glutamate transporter, VGluT2, in the macaque monkey auditory cortex. Journal of chemical neuroanatomy 37 19446630
2012 Acoustic overexposure increases the expression of VGLUT-2 mediated projections from the lateral vestibular nucleus to the dorsal cochlear nucleus. PloS one 36 22570693
2010 Vesicular glutamate transporter 2 (VGLUT2) is co-stored with PACAP in projections from the rat melanopsin-containing retinal ganglion cells. Cell and tissue research 36 20339872
2009 Reduced VGLUT2 expression increases motor neuron viability in Sod1(G93A) mice. Neurobiology of disease 35 19770042
2008 Comparison of the ontogeny of the vesicular glutamate transporter 3 (VGLUT3) with VGLUT1 and VGLUT2 in the rat retina. Brain research 34 18482716
2018 Targeting VGLUT2 in Mature Dopamine Neurons Decreases Mesoaccumbal Glutamatergic Transmission and Identifies a Role for Glutamate Co-release in Synaptic Plasticity by Increasing Baseline AMPA/NMDA Ratio. Frontiers in neural circuits 32 30210305
2007 Antipsychotics increase vesicular glutamate transporter 2 (VGLUT2) expression in thalamolimbic pathways. Neuropharmacology 31 18155072
2020 Mu opioid receptors on vGluT2-expressing glutamatergic neurons modulate opioid reward. Addiction biology 30 32686251
2004 Independent inputs by VGLUT2- and VGLUT3-positive glutamatergic terminals onto rat sympathetic preganglionic neurons. Neuroreport 30 15094498
2020 VGluT2 Expression in Dopamine Neurons Contributes to Postlesional Striatal Reinnervation. The Journal of neuroscience : the official journal of the Society for Neuroscience 29 32928885
2012 Ultrastructural characterization of the mesostriatal dopamine innervation in mice, including two mouse lines of conditional VGLUT2 knockout in dopamine neurons. The European journal of neuroscience 29 22330100
2021 VGLUT2 Is a Determinant of Dopamine Neuron Resilience in a Rotenone Model of Dopamine Neurodegeneration. The Journal of neuroscience : the official journal of the Society for Neuroscience 28 33893220
2019 Developmental Co-expression of Vglut2 and Nurr1 in a Mes-Di-Encephalic Continuum Preceeds Dopamine and Glutamate Neuron Specification. Frontiers in cell and developmental biology 28 31850343
2018 VGAT and VGLUT2 expression in MCH and orexin neurons in double transgenic reporter mice. IBRO reports 28 30155524
2018 VGLUT2 Functions as a Differential Marker for Hippocampal Output Neurons. Frontiers in cellular neuroscience 28 30333731
2010 Coexpression of VGLUT1 and VGLUT2 in trigeminothalamic projection neurons in the principal sensory trigeminal nucleus of the rat. The Journal of comparative neurology 28 20533365
2007 Morphology and electrophysiological properties of hamster spinal dorsal horn neurons that express VGLUT2 and enkephalin. The Journal of comparative neurology 27 17299755
2015 Changes in VGLUT2 expression and function in pain-related supraspinal regions correlate with the pathogenesis of neuropathic pain in a mouse spared nerve injury model. Brain research 26 26300222
2019 Differential Expression of VGLUT2 in Mouse Mesopontine Cholinergic Neurons. eNeuro 23 31366590
2017 VGLUT2 Trafficking Is Differentially Regulated by Adaptor Proteins AP-1 and AP-3. Frontiers in cellular neuroscience 22 29123471
2011 Immunohistochemical localization of vesicular glutamate transporter 2 (vGluT2) in the central nervous system of the pigeon (Columba livia). The Journal of comparative neurology 22 21618220
2005 Up-regulation of VGLUT2 expression in hypothalamic-neurohypophysial neurons of the rat following osmotic challenge. The European journal of neuroscience 22 16101749
2018 Eliminating the VGlut2-Dependent Glutamatergic Transmission of Parvalbumin-Expressing Neurons Leads to Deficits in Locomotion and Vocalization, Decreased Pain Sensitivity, and Increased Dominance. Frontiers in behavioral neuroscience 20 30072881
2013 Differential expression of VGLUT1 or VGLUT2 in the trigeminothalamic or trigeminocerebellar projection neurons in the rat. Brain structure & function 20 23380804
2002 Transporters in the neurohypophysial neuroendocrine system, with special reference to vesicular glutamate transporters (BNPI and DNPI): a review. Microscopy research and technique 20 11810715
2020 Heterogeneous expression of dopaminergic markers and Vglut2 in mouse mesodiencephalic dopaminergic nuclei A8-A13. The Journal of comparative neurology 19 32869307
2006 Immunohistochemical localization of the vesicular glutamate transporter VGLUT2 in the developing and adult mouse claustrum. Journal of chemical neuroanatomy 19 16434168
2020 Dysregulation of EAAT2 and VGLUT2 Spinal Glutamate Transports via Histone Deacetylase 2 (HDAC2) Contributes to Paclitaxel-induced Painful Neuropathy. Molecular cancer therapeutics 18 32847971
2019 SNAP-25 Contributes to Neuropathic Pain by Regulation of VGLuT2 Expression in Rats. Neuroscience 18 31705888
2016 Changes in VGLUT1 and VGLUT2 expression in rat dorsal root ganglia and spinal cord following spared nerve injury. Neurochemistry international 18 27210824
2014 Increased hippocampal excitability and impaired spatial memory function in mice lacking VGLUT2 selectively in neurons defined by tyrosine hydroxylase promoter activity. Brain structure & function 18 24802380
2011 The metabotropic glutamate receptor antagonist 2-methyl-6-(phenylethynyl) pyridine decreases striatal VGlut2 expression in association with an attenuation of L-DOPA-induced dyskinesias. Synapse (New York, N.Y.) 18 21484883
2011 Some lumbar sympathetic neurons develop a glutamatergic phenotype after peripheral axotomy with a note on VGLUT₂-positive perineuronal baskets. Experimental neurology 17 21596036
2022 Roles of VGLUT2 and Dopamine/Glutamate Co-Transmission in Selective Vulnerability to Dopamine Neurodegeneration. ACS chemical neuroscience 16 34994539
2017 Blockade of TrkB receptors in the nucleus accumbens prior to heterotypic stress alters corticotropin-releasing hormone (CRH), vesicular glutamate transporter 2 (vGluT2) and glucocorticoid receptor (GR) within the mesolimbic pathway. Hormones and behavior 16 28257759
2019 Wnt1/β-catenin signaling upregulates spinal VGLUT2 expression to control neuropathic pain in mice. Neuropharmacology 15 31785260
2014 Expression of vesicular glutamate transporters VGLUT1 and VGLUT2 in the rat dental pulp and trigeminal ganglion following inflammation. PloS one 15 25290694
2015 mTOR signaling controls VGLUT2 expression to maintain pain hypersensitivity after tissue injury. Neuroscience 14 26362885
2012 VGluT2 and NMDAR1 expression in cells in the inflammatory infiltrates in experimentally induced myositis: evidence of local glutamate signaling suggests autocrine/paracrine effects in an overuse injury model. Inflammation 14 21193952
2019 SLC17A6/7/8 Vesicular Glutamate Transporter Homologs in Nematodes. Genetics 13 31776169
2013 Haploinsufficiency of VGluT1 but not VGluT2 impairs extinction of spatial preference and response suppression. Behavioural brain research 13 23396167
2017 Optogenetic activation of VGLUT2-expressing excitatory neurons blocks epileptic seizure-like activity in the mouse entorhinal cortex. Scientific reports 12 28230208
2015 Expression of Vesicular Glutamate Transporter 2 (vGluT2) on Large Dense-Core Vesicles within GnRH Neuroterminals of Aging Female Rats. PloS one 12 26053743
2021 Deletion of VGLUT2 in midbrain dopamine neurons attenuates dopamine and glutamate responses to methamphetamine in mice. Pharmacology, biochemistry, and behavior 11 33444596
2018 VGLUT1 or VGLUT2 mRNA-positive neurons in spinal trigeminal nucleus provide collateral projections to both the thalamus and the parabrachial nucleus in rats. Molecular brain 11 29650024
2011 Non-peptidergic small diameter primary afferents expressing VGluT2 project to lamina I of mouse spinal dorsal horn. Molecular pain 11 22152428
2008 Coexpression of the mu-opioid receptor splice variant MOR1C and the vesicular glutamate transporter 2 (VGLUT2) in rat central nervous system. The Journal of comparative neurology 11 18381590
2007 Analysis of a vesicular glutamate transporter (VGLUT2) supports a cell-leakage mode in addition to vesicular packaging. Neurochemical research 11 18080752
2019 VGLUT2 rs2290045 genotype moderates environmental sensitivity to alcohol-related problems in three samples of youths. European child & adolescent psychiatry 10 30805764
2010 Resequencing of the vesicular glutamate transporter 2 gene (VGLUT2) reveals some rare genetic variants that may increase the genetic burden in schizophrenia. Schizophrenia research 10 20541370
2024 VGluT2 neuron subtypes in the paraventricular thalamic nucleus regulate depression in paraquat-induced Parkinson's disease. Journal of hazardous materials 9 38735189
2022 Dysregulation of Vesicular Glutamate Transporter VGluT2 via BDNF/TrkB Pathway Contributes to Morphine Tolerance in Mice. Frontiers in pharmacology 9 35559256
2020 VGLUT2-expressing neurons in the vestibular nuclear complex mediate gravitational stress-induced hypothermia in mice. Communications biology 9 32385401
2020 Coexpression of VGLUT1 and VGLUT2 in precerebellar neurons in the lateral reticular nucleus of the rat. Brain research bulletin 9 32562720
2006 VGLUT2 expression is up-regulated in neurohypophysial vasopressin neurons of the rat after osmotic stimulation. Neuroscience research 9 16842872

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