The NCA sodium leak channel is required for persistent motor circuit activity that sustains locomotion.

Shangbang Gao,Sihui Guan,Jennifer K Pirri,Mei Zhen,Mark J Alkema,Taizo Kawano,Michelle D Po,Lin Xie

doi:10.1038/ncomms7323

Abstract

Persistent neural activity, a sustained circuit output that outlasts the stimuli, underlies short-term or working memory, as well as various mental representations. Molecular mechanisms that underlie persistent activity are not well understood. Combining in situ whole-cell patch clamping and quantitative locomotion analyses, we show here that the Caenorhabditis elegans neuromuscular system exhibits persistent rhythmic activity, and such an activity contributes to the sustainability of basal locomotion, and the maintenance of acceleration after stimulation. The NALCN family sodium leak channel regulates the resting membrane potential and excitability of invertebrate and vertebrate neurons. Our molecular genetics and electrophysiology analyses show that the C. elegans NALCN, NCA, activates a premotor interneuron network to potentiate persistent motor circuit activity and to sustain C. elegans locomotion. Collectively, these results reveal a mechanism for, and physiological function of, persistent neural activity using a simple animal model, providing potential mechanistic clues for working memory in other systems.

Highlights

Persistent neural activity, a sustained circuit output that outlasts the stimuli, underlies shortterm or working memory, as well as various mental representations
A C. elegans electrophysiology preparation was developed[42], modified and optimized in recent years, including the adaption of optogenetic stimulation of sensory, motor and premotor interneurons[43,44,45,46], to allow for quantitative assessment of the physiological properties of the C. elegans motor system. These studies determined that the C. elegans musculatures receive excitatory cholinergic inputs to activate calcium-driven action potential bursts in body wall muscles and sustained muscle contraction, whereas inhibitory GABAergic inputs lead to the hyperpolarization of the muscle membrane potential, inhibition of action potential firing and muscle relaxation
Electrophysiology analyses on both in vivo and in vitro vertebrate preparations have mainly relied on pharmacological interventions to reveal mechanisms for persistent neural activity

Summary

Introduction

Persistent neural activity, a sustained circuit output that outlasts the stimuli, underlies shortterm or working memory, as well as various mental representations. Our molecular genetics and electrophysiology analyses show that the C. elegans NALCN, NCA, activates a premotor interneuron network to potentiate persistent motor circuit activity and to sustain C. elegans locomotion These results reveal a mechanism for, and physiological function of, persistent neural activity using a simple animal model, providing potential mechanistic clues for working memory in other systems. Single unit recordings from the primate prefrontal cortex neurons detected sustained neuronal firing during the late phase of a delayed response task[2,3] Since these initial findings, persistent neural activities that outlast the input stimuli have been found in multiple brain regions, and implicated in working memory and motor planning[4,5,6,7]. Its absence leads to the hyperpolarization of mouse hippocampal and cortical neurons[34,40], Caenorhabditis elegans premotor interneurons[37] and snail respiratory pacemaker neurons[36], revealing its conserved role in establishing neuronal resting membrane potential

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Results

Conclusion