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TheDrosophilaMetabotropic Glutamate Receptor DmGluRA Regulates Activity-Dependent Synaptic Facilitation and Fine Synaptic Morphology

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Title: TheDrosophilaMetabotropic Glutamate Receptor DmGluRA Regulates Activity-Dependent Synaptic Facilitation and Fine Synaptic Morphology
Authors: Bogdanik, Laurent, Mohrmann, Ralf, Ramaekers, Ariane, Bockaert, Joël, Grau, Yves, Broadie, Kendal, Parmentier, Marie-Laure
Source: The Journal of Neuroscience. 24:9105-9116
Publisher Information: Society for Neuroscience, 2004.
Publication Year: 2004
Subject Terms: 0301 basic medicine, Patch-Clamp Techniques, Action Potentials -- physiology, Neuromuscular Junction, Presynaptic Terminals, Action Potentials, Glutamic Acid, Genetically Modified, Synapses -- metabolism -- physiology -- ultrastructure, Receptors, Metabotropic Glutamate, Synaptic Transmission, Feedback, Animals, Genetically Modified, 03 medical and health sciences, Receptors, Animals, Drosophila Proteins, Drosophila Proteins -- genetics -- metabolism, Physiological -- physiology, GTP-Binding Protein beta Subunits -- metabolism, Neuronal Plasticity -- genetics -- physiology, Feedback, Physiological, 0303 health sciences, Neuronal Plasticity, Glutamic Acid -- metabolism, Neuromuscular Junction -- metabolism -- physiology -- ultrastructure, GTP-Binding Protein beta Subunits, Synaptic Transmission -- physiology, Electric Stimulation, Drosophila melanogaster, Larva, Mutation, Synapses, Presynaptic Terminals -- metabolism -- ultrastructure, Biologie, Metabotropic Glutamate -- genetics -- metabolism -- physiology
Description: In vertebrates, several groups of metabotropic glutamate receptors (mGluRs) are known to modulate synaptic properties. In contrast, theDrosophilagenome encodes a single functional mGluR (DmGluRA), an ortholog of vertebrate group II mGluRs, greatly expediting the functional characterization of mGluR-mediated signaling in the nervous system. We show here that DmGluRA is expressed at the glutamatergic neuromuscular junction (NMJ), localized in periactive zones of presynaptic boutons but excluded from active sites. NullDmGluRAmutants are completely viable, and all of the basal NMJ synaptic transmission properties are normal. In contrast,DmGluRAmutants display approximately a threefold increase in synaptic facilitation during short stimulus trains. Prolonged stimulus trains result in very strongly increased (∼10-fold) augmentation, including the appearance of asynchronous, bursting excitatory currents never observed in wild type. Both defects are rescued by expression of DmGluRA only in the neurons, indicating a specific presynaptic requirement. These phenotypes are reminiscent of hyperexcitable mutants, suggesting a role of DmGluRA signaling in the regulation of presynaptic excitability properties. The mutant phenotypes could not be replicated by acute application of mGluR antagonists, suggesting that DmGluRA regulates the development of presynaptic properties rather than directly controlling short-term modulation.DmGluRAmutants also display mild defects in NMJ architecture: a decreased number of synaptic boutons accompanied by an increase in mean bouton size. These morphological changes bidirectionally correlate with DmGluRA levels in the presynaptic terminal. These data reveal the following two roles for DmGluRA in presynaptic mechanisms: (1) modulation of presynaptic excitability properties important for the control of activity-dependent neurotransmitter release and (2) modulation of synaptic architecture.
Document Type: Article
File Description: 1 full-text file(s): application/pdf
Language: English
ISSN: 1529-2401
0270-6474
DOI: 10.1523/jneurosci.2724-04.2004
Access URL: https://europepmc.org/articles/pmc6730051?pdf=render
https://pubmed.ncbi.nlm.nih.gov/15483129
https://europepmc.org/article/MED/15483129
https://www.jneurosci.org/content/24/41/9105.full.pdf
https://www.jneurosci.org/content/jneuro/24/41/9105.full.pdf
http://www.jneurosci.org/content/24/41/9105.abstract
http://www.ncbi.nlm.nih.gov/pubmed/15483129
https://www.jneurosci.org/content/24/41/9105
Rights: CC BY NC SA
Accession Number: edsair.doi.dedup.....e37ed1677be3634b087bc4d4741ecc9e
Database: OpenAIRE
Description
Abstract:In vertebrates, several groups of metabotropic glutamate receptors (mGluRs) are known to modulate synaptic properties. In contrast, theDrosophilagenome encodes a single functional mGluR (DmGluRA), an ortholog of vertebrate group II mGluRs, greatly expediting the functional characterization of mGluR-mediated signaling in the nervous system. We show here that DmGluRA is expressed at the glutamatergic neuromuscular junction (NMJ), localized in periactive zones of presynaptic boutons but excluded from active sites. NullDmGluRAmutants are completely viable, and all of the basal NMJ synaptic transmission properties are normal. In contrast,DmGluRAmutants display approximately a threefold increase in synaptic facilitation during short stimulus trains. Prolonged stimulus trains result in very strongly increased (∼10-fold) augmentation, including the appearance of asynchronous, bursting excitatory currents never observed in wild type. Both defects are rescued by expression of DmGluRA only in the neurons, indicating a specific presynaptic requirement. These phenotypes are reminiscent of hyperexcitable mutants, suggesting a role of DmGluRA signaling in the regulation of presynaptic excitability properties. The mutant phenotypes could not be replicated by acute application of mGluR antagonists, suggesting that DmGluRA regulates the development of presynaptic properties rather than directly controlling short-term modulation.DmGluRAmutants also display mild defects in NMJ architecture: a decreased number of synaptic boutons accompanied by an increase in mean bouton size. These morphological changes bidirectionally correlate with DmGluRA levels in the presynaptic terminal. These data reveal the following two roles for DmGluRA in presynaptic mechanisms: (1) modulation of presynaptic excitability properties important for the control of activity-dependent neurotransmitter release and (2) modulation of synaptic architecture.
ISSN:15292401
02706474
DOI:10.1523/jneurosci.2724-04.2004