vesicular glutamate transport protein 2


Summary: A vesicular glutamate transporter protein that is predominately expressed in the DIENCEPHALON and lower brainstem regions of the CENTRAL NERVOUS SYSTEM.

Top Publications

  1. Doyle S, Pyndiah S, De Gois S, Erickson J. 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. J Biol Chem. 2010;285:14366-76 pubmed publisher
  2. Vetrivelan R, Fuller P, Tong Q, Lu J. Medullary circuitry regulating rapid eye movement sleep and motor atonia. J Neurosci. 2009;29:9361-9 pubmed publisher
    ..These findings, together, demonstrate that SOM glutamatergic neurons comprise key elements of the medullary circuitry mediating REM atonia. ..
  3. Nakamura K, Hioki H, Fujiyama F, Kaneko T. Postnatal changes of vesicular glutamate transporter (VGluT)1 and VGluT2 immunoreactivities and their colocalization in the mouse forebrain. J Comp Neurol. 2005;492:263-88 pubmed
  4. Hegarty D, Tonsfeldt K, Hermes S, Helfand H, Aicher S. Differential localization of vesicular glutamate transporters and peptides in corneal afferents to trigeminal nucleus caudalis. J Comp Neurol. 2010;518:3557-69 pubmed publisher
    ..Our results are consistent with a growing literature suggesting that glutamatergic and peptidergic sensory afferents may be distinct populations. ..
  5. Landry M, Bouali Benazzouz R, El Mestikawy S, Ravassard P, Nagy F. Expression of vesicular glutamate transporters in rat lumbar spinal cord, with a note on dorsal root ganglia. J Comp Neurol. 2004;468:380-94 pubmed
  6. Ottem E, Godwin J, Krishnan S, Petersen S. Dual-phenotype GABA/glutamate neurons in adult preoptic area: sexual dimorphism and function. J Neurosci. 2004;24:8097-105 pubmed
    ..Thus, we propose a new model for ovulation that includes dual-phenotype GABA/glutamate neurons as central transducers of hormonal and neural signals to GnRH neurons. ..
  7. Tordera R, Pei Q, Sharp T. Evidence for increased expression of the vesicular glutamate transporter, VGLUT1, by a course of antidepressant treatment. J Neurochem. 2005;94:875-83 pubmed
    ..These data suggest that a course of antidepressant drug or ECS treatment increases expression of VGLUT1, a key gene involved in the regulation of glutamate secretion. ..
  8. Kawano M, Kawasaki A, Sakata Haga H, Fukui Y, Kawano H, Nogami H, et al. Particular subpopulations of midbrain and hypothalamic dopamine neurons express vesicular glutamate transporter 2 in the rat brain. J Comp Neurol. 2006;498:581-92 pubmed
    ..These results indicate that VGLUT2 is expressed in subsets of A10 and A11 dopamine neurons, which might release dopamine and glutamate separately from different varicosities in the majority of their single axons. ..
  9. Morris J, Konig P, Shimizu T, Jobling P, Gibbins I. Most peptide-containing sensory neurons lack proteins for exocytotic release and vesicular transport of glutamate. J Comp Neurol. 2005;483:1-16 pubmed
    ..These data raise the possibility that most peptide-containing sensory neurons may not normally release glutamate as a transmitter. ..

More Information


  1. Maxwell D, Belle M, Cheunsuang O, Stewart A, Morris R. Morphology of inhibitory and excitatory interneurons in superficial laminae of the rat dorsal horn. J Physiol. 2007;584:521-33 pubmed
    ..Our hypothesis appears to be correct only for islet cells. Other classes of cells have mixed actions, and in the case of vertical cells, the axonal projection appears to be a more important determinant of postsynaptic action. ..
  2. Dal Bo G, Bérubé Carrière N, Mendez J, Leo D, Riad M, Descarries L, et al. Enhanced glutamatergic phenotype of mesencephalic dopamine neurons after neonatal 6-hydroxydopamine lesion. Neuroscience. 2008;156:59-70 pubmed publisher
    ..They also support the hypothesis of co-release of glutamate and DA by mesencephalic neurons in vivo, at least in the developing brain. ..
  3. Schallier A, Massie A, Loyens E, Moechars D, Drinkenburg W, Michotte Y, et al. vGLUT2 heterozygous mice show more susceptibility to clonic seizures induced by pentylenetetrazol. Neurochem Int. 2009;55:41-4 pubmed publisher
    ..The threshold for PTZ-induced clonic seizure activity was also lower in the vGLUT2 HET mice. These results indicate, for the first time, that vGLUT2 is likely involved in the epileptogenesis of generalized seizures. ..
  4. Wallén Mackenzie A, Nordenankar K, Fejgin K, Lagerström M, Emilsson L, Fredriksson R, et al. Restricted cortical and amygdaloid removal of vesicular glutamate transporter 2 in preadolescent mice impacts dopaminergic activity and neuronal circuitry of higher brain function. J Neurosci. 2009;29:2238-51 pubmed publisher
  5. Zeng C, Nannapaneni N, Zhou J, Hughes L, Shore S. Cochlear damage changes the distribution of vesicular glutamate transporters associated with auditory and nonauditory inputs to the cochlear nucleus. J Neurosci. 2009;29:4210-7 pubmed publisher
  6. Zeng C, Shroff H, Shore S. Cuneate and spinal trigeminal nucleus projections to the cochlear nucleus are differentially associated with vesicular glutamate transporter-2. Neuroscience. 2011;176:142-51 pubmed publisher
  7. Kashani A, Lepicard E, Poirel O, Videau C, David J, Fallet Bianco C, et al. Loss of VGLUT1 and VGLUT2 in the prefrontal cortex is correlated with cognitive decline in Alzheimer disease. Neurobiol Aging. 2008;29:1619-30 pubmed
    ..Our results suggest that VGLUT1 expression in the prefrontal cortex could be used as a valuable neurochemical marker of dementia in AD. ..
  8. Tong Q, Ye C, McCrimmon R, Dhillon H, Choi B, Kramer M, et al. Synaptic glutamate release by ventromedial hypothalamic neurons is part of the neurocircuitry that prevents hypoglycemia. Cell Metab. 2007;5:383-93 pubmed
    ..Thus, glutamate release from VMH neurons is an important component of the neurocircuitry that functions to prevent hypoglycemia. ..
  9. Raju D, Shah D, Wright T, Hall R, Smith Y. Differential synaptology of vGluT2-containing thalamostriatal afferents between the patch and matrix compartments in rats. J Comp Neurol. 2006;499:231-43 pubmed
    ..These observations pave the way for understanding differential regulatory mechanisms of striatal outflow from the patch and matrix compartments by thalamostriatal afferents. ..
  10. Balschun D, Moechars D, Callaerts Vegh Z, Vermaercke B, Van Acker N, Andries L, et al. Vesicular glutamate transporter VGLUT1 has a role in hippocampal long-term potentiation and spatial reversal learning. Cereb Cortex. 2010;20:684-93 pubmed publisher
    ..Our data suggest a functional role of VGLUT1 in forms of hippocampal synaptic plasticity that are required to adapt and modify acquired spatial maps to external stimuli and changes. ..
  11. Kawasaki A, Shutoh F, Nogami H, Hisano S. VGLUT2 expression is up-regulated in neurohypophysial vasopressin neurons of the rat after osmotic stimulation. Neurosci Res. 2006;56:124-7 pubmed
    ..These results indicate that VGLUT2 is principally expressed in VP neurons and also in some OT neurons and that VGLUT2 in VP and OT neurons is involved in osmotic regulation. ..
  12. Shen Y, Liu X, Pleasure D, Deng W. Axon-glia synapses are highly vulnerable to white matter injury in the developing brain. J Neurosci Res. 2012;90:105-21 pubmed publisher
    ..More broadly, the study of white matter development and injury has general implications for a variety of neurological diseases, including PVL, stroke, spinal cord injury, and multiple sclerosis. ..
  13. Blaesse P, Ehrhardt S, Friauf E, Nothwang H. Developmental pattern of three vesicular glutamate transporters in the rat superior olivary complex. Cell Tissue Res. 2005;320:33-50 pubmed
    ..Our results imply a considerable amount of synaptic reorganization in the glutamatergic inputs to the SOC and suggest differential roles of VGLUTs during maturation and in adulthood. ..
  14. Li J, Baccei M. Pacemaker neurons within newborn spinal pain circuits. J Neurosci. 2011;31:9010-22 pubmed publisher
  15. Boulland J, Qureshi T, Seal R, Rafiki A, Gundersen V, Bergersen L, et al. Expression of the vesicular glutamate transporters during development indicates the widespread corelease of multiple neurotransmitters. J Comp Neurol. 2004;480:264-80 pubmed
    ..In skeletal muscle, VGLUT3 localizes to granular organelles in the axon terminal as well as in the muscle sarcoplasm. The results suggest novel mechanisms and roles for regulated transmitter release. ..
  16. Schuske K, Jorgensen E. Neuroscience. Vesicular glutamate transporter--shooting blanks. Science. 2004;304:1750-2 pubmed
  17. Fremeau R, Voglmaier S, Seal R, Edwards R. VGLUTs define subsets of excitatory neurons and suggest novel roles for glutamate. Trends Neurosci. 2004;27:98-103 pubmed
    ..VGLUT3 also differs from VGLUT1 and VGLUT2 in its subcellular location, with somatodendritic as well as axonal expression. ..
  18. Liu Y, Abdel Samad O, Zhang L, Duan B, Tong Q, Lopes C, et al. VGLUT2-dependent glutamate release from nociceptors is required to sense pain and suppress itch. Neuron. 2010;68:543-56 pubmed publisher
    ..Our studies suggest that synaptic glutamate release from a group of peripheral nociceptors is required to sense pain and suppress itch. Elimination of VGLUT2 in these nociceptors creates a mouse model of chronic neurogenic itch. ..
  19. Schnell S, Wessendorf M. Coexpression of the mu-opioid receptor splice variant MOR1C and the vesicular glutamate transporter 2 (VGLUT2) in rat central nervous system. J Comp Neurol. 2008;508:542-64 pubmed publisher
    ..We hypothesize that activation of MOR(1C) by mu-opioid agonists at some glutamatergic terminals may be a mechanism by which glutamate release is inhibited. ..
  20. Fremeau R, Kam K, Qureshi T, Johnson J, Copenhagen D, Storm Mathisen J, et al. Vesicular glutamate transporters 1 and 2 target to functionally distinct synaptic release sites. Science. 2004;304:1815-9 pubmed
    ..The loss of VGLUT1 also reduced the reserve pool of synaptic vesicles. Thus, VGLUT1 plays an unanticipated role in membrane trafficking at the nerve terminal. ..
  21. Barroso Chinea P, Castle M, Aymerich M, Perez Manso M, Erro E, Tuñon T, et al. Expression of the mRNAs encoding for the vesicular glutamate transporters 1 and 2 in the rat thalamus. J Comp Neurol. 2007;501:703-15 pubmed
    ..These results call for a reappraisal of the previously held concept regarding the mutually exclusive distribution of VGLUT transporters in the central nervous system. ..
  22. Moechars D, Weston M, Leo S, Callaerts Vegh Z, Goris I, Daneels G, et al. Vesicular glutamate transporter VGLUT2 expression levels control quantal size and neuropathic pain. J Neurosci. 2006;26:12055-66 pubmed
  23. De Gois S, Schafer M, Defamie N, Chen C, Ricci A, Weihe E, et al. Homeostatic scaling of vesicular glutamate and GABA transporter expression in rat neocortical circuits. J Neurosci. 2005;25:7121-33 pubmed
  24. Real M, Dávila J, Guirado S. Immunohistochemical localization of the vesicular glutamate transporter VGLUT2 in the developing and adult mouse claustrum. J Chem Neuroanat. 2006;31:169-77 pubmed
    ..These VGLUT2-immunoreactive boutons are observed as early as E16.5 and may be related to thalamo-claustral incoming fibers. ..
  25. Wallén Mackenzie A, Gezelius H, Thoby Brisson M, Nygård A, Enjin A, Fujiyama F, et al. Vesicular glutamate transporter 2 is required for central respiratory rhythm generation but not for locomotor central pattern generation. J Neurosci. 2006;26:12294-307 pubmed
    ..Hence, the present study identifies VGLUT2-mediated signaling as an obligatory component of the developing respiratory rhythm generator. ..
  26. Hur E, Zaborszky L. Vglut2 afferents to the medial prefrontal and primary somatosensory cortices: a combined retrograde tracing in situ hybridization study [corrected]. J Comp Neurol. 2005;483:351-73 pubmed
    ..The extrathalamic Vglut2 corticopetal projections, together with the thalamic intralaminar-midline Vglut2 corticopetal projections, may participate in diffuse activation of the neocortex...
  27. Li T, Bai L, Li J, Igarashi S, Ghishan F. Sp1 is required for glucose-induced transcriptional regulation of mouse vesicular glutamate transporter 2 gene. Gastroenterology. 2008;134:1994-2003 pubmed publisher
    ..This leads to increased binding activity of Sp1 to the mVGLUT2 promoter and results in activation of the gene. We cloned the mouse VGLUT2 promoter and showed a novel molecular mechanism of glucose-induced mVGLUT2 transcription. ..
  28. Stella S, Li S, Sabatini A, Vila A, Brecha N. Comparison of the ontogeny of the vesicular glutamate transporter 3 (VGLUT3) with VGLUT1 and VGLUT2 in the rat retina. Brain Res. 2008;1215:20-9 pubmed publisher
  29. Neal Perry G, Zeevalk G, Shu J, Etgen A. Restoration of the luteinizing hormone surge in middle-aged female rats by altering the balance of GABA and glutamate transmission in the medial preoptic area. Biol Reprod. 2008;79:878-88 pubmed publisher
  30. Polgár E, Al Ghamdi K, Todd A. Two populations of neurokinin 1 receptor-expressing projection neurons in lamina I of the rat spinal cord that differ in AMPA receptor subunit composition and density of excitatory synaptic input. Neuroscience. 2010;167:1192-204 pubmed publisher
  31. Brumovsky P, Watanabe M, Hokfelt T. Expression of the vesicular glutamate transporters-1 and -2 in adult mouse dorsal root ganglia and spinal cord and their regulation by nerve injury. Neuroscience. 2007;147:469-90 pubmed
    ..J Comp Neurol 483:1-16], we speculate that virtually all DRG neurons in adult mouse express VGLUTs and use glutamate as transmitter. ..
  32. Billups B. Colocalization of vesicular glutamate transporters in the rat superior olivary complex. Neurosci Lett. 2005;382:66-70 pubmed
    ..As the abundance of VGLUT determines the quantal size, this up-regulation will increase excitatory postsynaptic currents (EPSCs) and have influences on synaptic physiology. ..
  33. Alvarez F, Villalba R, Zerda R, Schneider S. Vesicular glutamate transporters in the spinal cord, with special reference to sensory primary afferent synapses. J Comp Neurol. 2004;472:257-80 pubmed
    ..These results indicate a diversity of VGLUT isoform combinations expressed in different spinal primary afferents. ..
  34. Polgár E, Al Khater K, Shehab S, Watanabe M, Todd A. 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. J Neurosci. 2008;28:13150-60 pubmed publisher
    ..Our results also provide the first evidence that postsynaptic GluR4-containing AMPA receptors are involved in spinal nociceptive transmission. ..
  35. Fuller P, Fuller P, Sherman D, Pedersen N, Saper C, Lu J. Reassessment of the structural basis of the ascending arousal system. J Comp Neurol. 2011;519:933-56 pubmed publisher
  36. Wootz H, Enjin A, Wallén Mackenzie A, Lindholm D, Kullander K. Reduced VGLUT2 expression increases motor neuron viability in Sod1(G93A) mice. Neurobiol Dis. 2010;37:58-66 pubmed publisher
    ..Taken together, this suggests that reduced levels of VGLUT2 decrease motor neuron degeneration but do not prevent loss of motor neuron function in the SOD1(G93A) mouse model for ALS. ..
  37. He H, Mahnke A, Doyle S, Fan N, Wang C, Hall B, et al. Neurodevelopmental role for VGLUT2 in pyramidal neuron plasticity, dendritic refinement, and in spatial learning. J Neurosci. 2012;32:15886-901 pubmed publisher
  38. Scherrer G, Low S, Wang X, Zhang J, Yamanaka H, Urban R, et al. VGLUT2 expression in primary afferent neurons is essential for normal acute pain and injury-induced heat hypersensitivity. Proc Natl Acad Sci U S A. 2010;107:22296-301 pubmed publisher
  39. Ito T, Bishop D, Oliver D. Expression of glutamate and inhibitory amino acid vesicular transporters in the rodent auditory brainstem. J Comp Neurol. 2011;519:316-40 pubmed publisher
    ..These data show that the expression of the VGLUT1/2 and VIAAT genes can identify different subsets of auditory neurons. This may facilitate the identification of different components in auditory circuits. ..
  40. Yasaka T, Tiong S, Hughes D, Riddell J, Todd A. Populations of inhibitory and excitatory interneurons in lamina II of the adult rat spinal dorsal horn revealed by a combined electrophysiological and anatomical approach. Pain. 2010;151:475-88 pubmed publisher
    ..Combining this approach with identification of other neurochemical markers should allow further clarification of neuronal circuitry in the superficial dorsal horn. ..
  41. Hägglund M, Borgius L, Dougherty K, Kiehn O. Activation of groups of excitatory neurons in the mammalian spinal cord or hindbrain evokes locomotion. Nat Neurosci. 2010;13:246-52 pubmed publisher
  42. Leo S, Moechars D, Callaerts Vegh Z, D Hooge R, Meert T. Impairment of VGLUT2 but not VGLUT1 signaling reduces neuropathy-induced hypersensitivity. Eur J Pain. 2009;13:1008-17 pubmed publisher
    ..Together, these data suggest that VGLUT2, but not VGLUT1, plays a role in neuropathy-induced allodynia and hypersensitivity, and might be a therapeutic target to prevent and/or treat neuropathic pain. ..
  43. Herzog E, Gilchrist J, Gras C, Muzerelle A, Ravassard P, Giros B, et al. Localization of VGLUT3, the vesicular glutamate transporter type 3, in the rat brain. Neuroscience. 2004;123:983-1002 pubmed
    ..The distribution of VGLUT3 in the rat brain suggests an unsuspected function of vesicular glutamate transport in subsets of interneurons and in neuromodulatory neurons. ..
  44. Herzog E, Takamori S, Jahn R, Brose N, Wojcik S. Synaptic and vesicular co-localization of the glutamate transporters VGLUT1 and VGLUT2 in the mouse hippocampus. J Neurochem. 2006;99:1011-8 pubmed
    ..As the number of transporter molecules per vesicle affects quantal size, the developmental window where VGLUT1 and VGLUT2 are co-expressed may allow for greater plasticity in the control of quantal release. ..
  45. Wojcik S, Rhee J, Herzog E, Sigler A, Jahn R, Takamori S, et al. An essential role for vesicular glutamate transporter 1 (VGLUT1) in postnatal development and control of quantal size. Proc Natl Acad Sci U S A. 2004;101:7158-63 pubmed
    ..These results show that the expression level of VGLUTs determines the amount of glutamate that is loaded into vesicles and released and thereby regulates the efficacy of neurotransmission. ..
  46. Mangin J, Li P, Scafidi J, Gallo V. Experience-dependent regulation of NG2 progenitors in the developing barrel cortex. Nat Neurosci. 2012;15:1192-4 pubmed publisher
    ..Thus, early sensory experience regulates thalamocortical innervation on NG2 cells, as well as their proliferation and distribution during development. ..
  47. Oliveira A, Hydling F, Olsson E, Shi T, Edwards R, Fujiyama F, et al. Cellular localization of three vesicular glutamate transporter mRNAs and proteins in rat spinal cord and dorsal root ganglia. Synapse. 2003;50:117-29 pubmed
    ..VGLUT1 is mainly present in primary afferents from large, CGRP-negative DRG neurons, VGLUT2 has mainly a local origin, and VGLUT3 fibers probably have a supraspinal origin. ..
  48. Miyazaki T, Fukaya M, Shimizu H, Watanabe M. Subtype switching of vesicular glutamate transporters at parallel fibre-Purkinje cell synapses in developing mouse cerebellum. Eur J Neurosci. 2003;17:2563-72 pubmed
  49. Li J, Xiong K, Dong Y, Fujiyama F, Kaneko T, Mizuno N. Vesicular glutamate transporters, VGluT1 and VGluT2, in the trigeminal ganglion neurons of the rat, with special reference to coexpression. J Comp Neurol. 2003;463:212-20 pubmed
    ..Some of these axon terminals were confirmed to form the central core of the synaptic glomerulus. These results indicated that VGluT1 and VGluT2 are coexpressed in the cell bodies and axon terminals in most trigeminal ganglion neurons. ..
  50. Ziegler D, Cullinan W, Herman J. Distribution of vesicular glutamate transporter mRNA in rat hypothalamus. J Comp Neurol. 2002;448:217-29 pubmed
    ..Our data support a major role for hypothalamic glutamatergic neurons in regulation of all aspects of hypothalamic function. ..
  51. Kaneko T, Fujiyama F. Complementary distribution of vesicular glutamate transporters in the central nervous system. Neurosci Res. 2002;42:243-50 pubmed
    ..This complementary distribution might suggest that the two VGluTs have an as yet unknown difference in functions. ..
  52. Todd A, Hughes D, Polgar E, Nagy G, Mackie M, Ottersen O, et al. 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. Eur J Neurosci. 2003;17:13-27 pubmed
    ..As all primary afferents are thought to be glutamatergic, this raises the possibility that unmyelinated afferents, most of which are nociceptors, express a different vesicular glutamate transporter. ..
  53. Stornetta R, Rosin D, Wang H, Sevigny C, Weston M, Guyenet P. A group of glutamatergic interneurons expressing high levels of both neurokinin-1 receptors and somatostatin identifies the region of the pre-Bötzinger complex. J Comp Neurol. 2003;455:499-512 pubmed
    ..A subgroup of these cells contains high levels of SST and NK1R immunoreactivity in their somata. These glutamatergic interneurons identify a narrow region of the RVLM that appears to be coextensive with the pre-BötC of adult rats. ..