Glutamate spillover in C. elegans triggers repetitive behavior through presynaptic activation of MGL-2/mGluR5 - Sorbonne Université Access content directly
Journal Articles Nature Communications Year : 2019

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

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 inter-neuron 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.

Domains

Neurobiology
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Dates and versions

hal-02122223 , version 1 (07-05-2019)

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Menachem Katz, Francis Corson, Wolfgang Keil, Anupriya Singhal, Andrea Bae, et al.. Glutamate spillover in C. elegans triggers repetitive behavior through presynaptic activation of MGL-2/mGluR5. Nature Communications, 2019, 10, pp.1882. ⟨10.1038/s41467-019-09581-4⟩. ⟨hal-02122223⟩
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