| RRC ID |
59517
|
| Author |
Katz M, Corson F, Keil W, Singhal A, Bae A, Lu Y, Liang Y, Shaham S.
|
| Title |
Glutamate spillover in C. elegans triggers repetitive behavior through presynaptic activation of MGL-2/mGluR5.
|
| Journal |
Nat Commun
|
| 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.
|
| Volume |
10(1)
|
| Pages |
1882
|
| Published |
2019-4-23
|
| DOI |
10.1038/s41467-019-09581-4
|
| PII |
10.1038/s41467-019-09581-4
|
| PMID |
31015396
|
| PMC |
PMC6478929
|
| MeSH |
Animals
Animals, Genetically Modified
Behavior, Animal / physiology*
Caenorhabditis elegans / physiology*
Caenorhabditis elegans Proteins / metabolism*
Datasets as Topic
Excitatory Amino Acid Transporter 2 / metabolism
Gene Expression Profiling
Glutamic Acid / metabolism*
Interneurons / metabolism
Locomotion / physiology
Models, Animal
Presynaptic Terminals / physiology*
Receptor, Metabotropic Glutamate 5
Receptors, Metabotropic Glutamate / genetics
Receptors, Metabotropic Glutamate / metabolism*
|
| IF |
11.878
|
| Times Cited |
5
|
| Resource |
| C.elegans |
tm355
tm1811 |
