Journal ArticleDOI
The vesicular glutamate transporter VGLUT3 synergizes striatal acetylcholine tone
Christelle Gras,Bénédicte Amilhon,Bénédicte Amilhon,Eve M. Lepicard,Eve M. Lepicard,Odile Poirel,Odile Poirel,Jacqueline Vinatier,Jacqueline Vinatier,Marc Herbin,Sylvie Dumas,Eleni T. Tzavara,Eleni T. Tzavara,Mark R. Wade,George G. Nomikos,Naïma Hanoun,Françoise Saurini,M.L. Kemel,Bruno Gasnier,Bruno Giros,Bruno Giros,Bruno Giros,Salah El Mestikawy,Salah El Mestikawy,Salah El Mestikawy +24 more
TLDR
It is proposed that this vesicular synergy between two transmitters is the result of the unbalanced bioenergetics of VAChT, which requires anion co-entry for continuing vesicle filling.Abstract:
Three subtypes of vesicular transporters accumulate glutamate into synaptic vesicles to promote its vesicular release. One of the subtypes, VGLUT3, is expressed in neurons, including cholinergic striatal interneurons, that are known to release other classical transmitters. Here we showed that disruption of the Slc17a8 gene (also known as Vglut3) caused an unexpected hypocholinergic striatal phenotype. Vglut3(-/-) mice were more responsive to cocaine and less prone to haloperidol-induced catalepsy than wild-type littermates, and acetylcholine release was decreased in striatum slices lacking VGLUT3. These phenotypes were associated with a colocalization of VGLUT3 and the vesicular acetylcholine transporter (VAChT) in striatal synaptic vesicles and the loss of a synergistic effect of glutamate on vesicular acetylcholine uptake. We propose that this vesicular synergy between two transmitters is the result of the unbalanced bioenergetics of VAChT, which requires anion co-entry for continuing vesicular filling. Our study reveals a previously unknown effect of glutamate on cholinergic synapses with potential functional and pharmacological implications.read more
Citations
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Journal ArticleDOI
Pedunculopontine and laterodorsal tegmental nuclei contain distinct populations of cholinergic, glutamatergic and GABAergic neurons in the rat
Hui-Ling Wang,Marisela Morales +1 more
TL;DR: Over 95% of all PPTg/LDTg cholinergic neurons lack transcripts encoding either vGluT2 mRNA or GAD mRNA, which means co‐release of acetylcholine with either glutamate or GABA is unlikely to be a major factor in the interactions between acetyl choline, glutamate and GABA at the postsynaptic site.
Journal ArticleDOI
Injury-induced mechanical hypersensitivity requires C-low threshold mechanoreceptors
Rebecca P. Seal,Xingmei Wang,Yabo Guan,Srinivasa N. Raja,C. Jeffery Woodbury,Allan I. Basbaum,Robert H. Edwards +6 more
TL;DR: It is reported that a small subset of cells in the DRG expresses the low abundance vesicular glutamate transporter VGLUT3 (also known as SLC17A8), which impairs mechanical pain sensation and the mechanical hypersensitivity to normally innocuous stimuli that accompanies inflammation, nerve injury and trauma.
Journal ArticleDOI
Vesicular Glutamate Transport Promotes Dopamine Storage and Glutamate Corelease In Vivo
Thomas S. Hnasko,Nao Chuhma,Hui Zhang,Germaine Y. Goh,David Sulzer,Richard D. Palmiter,Stephen Rayport,Robert H. Edwards +7 more
TL;DR: The conditional knockout abolishes glutamate release from midbrain dopamine neurons in culture and severely reduces their excitatory synaptic output in mesoaccumbens slices, indicating a distinct, presynaptic mechanism to regulate quantal size.
Journal ArticleDOI
Metabolic control of vesicular glutamate transport and release.
Narinobu Juge,John A. Gray,Hiroshi Omote,Takaaki Miyaji,Tsuyoshi Inoue,Chiaki Hara,Hisayuki Uneyama,Robert H. Edwards,Roger A. Nicoll,Yoshinori Moriyama +9 more
TL;DR: An unsuspected link between metabolic state and excitatory neurotransmission through anion-dependent regulation of VGLUT activity is indicated through functional reconstitution of the purified VGLuts into proteoliposomes.
Journal ArticleDOI
From glutamate co-release to vesicular synergy: vesicular glutamate transporters
Salah El Mestikawy,Åsa Wallén-Mackenzie,Guillaume Fortin,Laurent Descarries,Louis-Eric Trudeau +4 more
TL;DR: Questions are raised about the morphological and functional organization of neuronal systems endowed with such a dual signalling capacity and the behavioural relevance of this co-phenotype is presently the focus of considerable interest.
References
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