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Glutamate spillover inC. eleganstriggers repetitive behavior through presynaptic activation of MGL-2/mGluR5
- Source :
- Nature Communications, Nature Communications, Nature Publishing Group, 2019, 10, pp.1882. ⟨10.1038/s41467-019-09581-4⟩, Nature Communications, Vol 10, Iss 1, Pp 1-13 (2019)
- Publication Year :
- 2018
- Publisher :
- Cold Spring Harbor Laboratory, 2018.
-
Abstract
- Glutamate is a major excitatory neurotransmitter, and impaired glutamate clearance following synaptic release promotes spillover, inducing extra-synaptic signaling. The effects of glutamate spillover on animal behavior and its neural correlates are poorly understood. We developed a glutamate spillover model in Caenorhabditis elegans by inactivating the conserved glial glutamate transporter GLT-1. GLT-1 loss drives aberrant repetitive locomotory reversal behavior through uncontrolled oscillatory release of glutamate onto AVA, a major interneuron governing reversals. Repetitive glutamate release and reversal behavior require the glutamate receptor MGL-2/mGluR5, expressed in RIM and other interneurons presynaptic to AVA. mgl-2 loss blocks oscillations and repetitive behavior; while RIM activation is sufficient to induce repetitive reversals in glt-1 mutants. Repetitive AVA firing and reversals require EGL-30/Gαq, an mGluR5 effector. Our studies reveal that cyclic autocrine presynaptic activation drives repetitive reversals following glutamate spillover. That mammalian GLT1 and mGluR5 are implicated in pathological motor repetition suggests a common mechanism controlling repetitive behaviors.<br />Katz and colleagues examine glutamate spillover effects on C. elegans behaviour. They show that impaired synaptic glutamate clearance in glial glutamate transporter mutants, causes presynaptic mgl-2/mGluR5 activation, generating postsynaptic neural activity oscillations driving repetitive behaviour.
- Subjects :
- 0301 basic medicine
[SDV.NEU.NB]Life Sciences [q-bio]/Neurons and Cognition [q-bio.NC]/Neurobiology
Mutant
Datasets as Topic
General Physics and Astronomy
02 engineering and technology
Receptors, Metabotropic Glutamate
Animals, Genetically Modified
0302 clinical medicine
Receptor
lcsh:Science
Caenorhabditis elegans
0303 health sciences
Multidisciplinary
Behavior, Animal
biology
Effector
Chemistry
Metabotropic glutamate receptor 5
Glutamate receptor
021001 nanoscience & nanotechnology
medicine.anatomical_structure
Excitatory Amino Acid Transporter 2
Gq alpha subunit
Models, Animal
0210 nano-technology
Locomotion
Interneuron
Receptor, Metabotropic Glutamate 5
Science
Presynaptic Terminals
Glutamic Acid
Neural circuits
Article
General Biochemistry, Genetics and Molecular Biology
03 medical and health sciences
Interneurons
medicine
Animals
Caenorhabditis elegans Proteins
Autocrine signalling
030304 developmental biology
Gene Expression Profiling
Glial biology
General Chemistry
biology.organism_classification
030104 developmental biology
biology.protein
lcsh:Q
Neuroscience
030217 neurology & neurosurgery
Subjects
Details
- ISSN :
- 20411723
- Database :
- OpenAIRE
- Journal :
- Nature Communications, Nature Communications, Nature Publishing Group, 2019, 10, pp.1882. ⟨10.1038/s41467-019-09581-4⟩, Nature Communications, Vol 10, Iss 1, Pp 1-13 (2019)
- Accession number :
- edsair.doi.dedup.....055601a747963a0e5c5bd942ab68f24f