The vesicular glutamate transporter VGLUT3 synergizes striatal acetylcholine tone
| Autor: | M.L. Kemel, George G. Nomikos, Naïma Hanoun, Christelle Gras, Salah El Mestikawy, Mark R. Wade, Françoise Saurini, Marc Herbin, Jacqueline Vinatier, Eve M. Lepicard, Eleni T. Tzavara, Bruno Gasnier, Bruno Giros, Bénédicte Amilhon, Sylvie Dumas, Odile Poirel |
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| Rok vydání: | 2007 |
| Předmět: |
Amino Acid Transport Systems
Acidic Vesicular Acetylcholine Transport Proteins Drug Resistance Presynaptic Terminals Down-Regulation Glutamic Acid Motor Activity Synaptic vesicle Synaptic Transmission Mice Organ Culture Techniques Dopamine Uptake Inhibitors Interneurons Vesicular acetylcholine transporter medicine Animals Mice Knockout Chemistry General Neuroscience Acetylcholine uptake Glutamate receptor Acetylcholine Corpus Striatum Rats SLC17A8 Cholinergic Synaptic Vesicles Neuroscience medicine.drug Antipsychotic Agents |
| Zdroj: | Nature neuroscience. 11(3) |
| ISSN: | 1097-6256 |
| Popis: | 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. |
| Databáze: | OpenAIRE |
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