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 and Shai Shaham ()
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Menachem Katz: The Rockefeller University
Francis Corson: Université Paris Diderot
Wolfgang Keil: The Rockefeller University
Anupriya Singhal: The Rockefeller University
Andrea Bae: The Rockefeller University
Yun Lu: The Rockefeller University
Yupu Liang: The Rockefeller University
Shai Shaham: The Rockefeller University

Nature Communications, 2019, vol. 10, issue 1, 1-13

Abstract: 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.

Date: 2019
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DOI: 10.1038/s41467-019-09581-4

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