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Glutamate spillover in C. elegans triggers repetitive behavior through presynaptic activation of MGL-2/mGluR5

Menachem Katz, Francis Corson, Wolfgang Keil, Anupriya Singhal, Andrea Bae, Yun Lu, Yupu Liang, Shai Shaham
doi: https://doi.org/10.1101/415828
Menachem Katz
The Rockefeller University;
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Francis Corson
Ecole Normale Superieure, CNRS, Universite Pierre et Marie Curie, Universite Paris Diderot
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Wolfgang Keil
The Rockefeller University;
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Anupriya Singhal
The Rockefeller University;
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Andrea Bae
The Rockefeller University;
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Yun Lu
The Rockefeller University;
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Yupu Liang
The Rockefeller University;
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Shai Shaham
The Rockefeller University;
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  • For correspondence: shaham@mail.rockefeller.edu
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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.

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The copyright holder for this preprint is the author/funder, who has granted bioRxiv a license to display the preprint in perpetuity. It is made available under a CC-BY-NC-ND 4.0 International license.
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Posted September 13, 2018.
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Glutamate spillover in C. elegans triggers repetitive behavior through presynaptic activation of MGL-2/mGluR5
Menachem Katz, Francis Corson, Wolfgang Keil, Anupriya Singhal, Andrea Bae, Yun Lu, Yupu Liang, Shai Shaham
bioRxiv 415828; doi: https://doi.org/10.1101/415828
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Glutamate spillover in C. elegans triggers repetitive behavior through presynaptic activation of MGL-2/mGluR5
Menachem Katz, Francis Corson, Wolfgang Keil, Anupriya Singhal, Andrea Bae, Yun Lu, Yupu Liang, Shai Shaham
bioRxiv 415828; doi: https://doi.org/10.1101/415828

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