title: The NCA sodium leak channel is required for persistent motor circuit activity that sustains locomotion.
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.
authors.affiliation: Lunenfeld-Tanenbaum Research Institute, Mount Sinai Hospital, Toronto, Ontario, Canada M5G 1X5.
authors.forename: Shangbang
authors.initials: S
authors.lastname: Gao
authors.affiliation: 1] Lunenfeld-Tanenbaum Research Institute, Mount Sinai Hospital, Toronto, Ontario, Canada M5G 1X5 [2] Institute of Medical Science, University of Toronto, Toronto, Ontario, Canada M5S 1A8.
authors.forename: Lin
authors.initials: L
authors.lastname: Xie
authors.affiliation: Lunenfeld-Tanenbaum Research Institute, Mount Sinai Hospital, Toronto, Ontario, Canada M5G 1X5.
authors.forename: Taizo
authors.initials: T
authors.lastname: Kawano
authors.affiliation: 1] Lunenfeld-Tanenbaum Research Institute, Mount Sinai Hospital, Toronto, Ontario, Canada M5G 1X5 [2] Department of Physiology, University of Toronto, Toronto, Ontario, Canada M5S 1A8.
authors.forename: Michelle D
authors.initials: MD
authors.lastname: Po
authors.affiliation: 1] Lunenfeld-Tanenbaum Research Institute, Mount Sinai Hospital, Toronto, Ontario, Canada M5G 1X5 [2] Institute of Medical Science, University of Toronto, Toronto, Ontario, Canada M5S 1A8.
authors.forename: Sihui
authors.initials: S
authors.lastname: Guan
authors.affiliation: 1] Lunenfeld-Tanenbaum Research Institute, Mount Sinai Hospital, Toronto, Ontario, Canada M5G 1X5 [2] Institute of Medical Science, University of Toronto, Toronto, Ontario, Canada M5S 1A8 [3] Department of Physiology, University of Toronto, Toronto, Ontario, Canada M5S 1A8 [4] Department of Molecular Genetics, University of Toronto, Toronto, Ontario, Canada M5S 1A8.
authors.forename: Mei
authors.initials: M
authors.lastname: Zhen
authors.forename: Jennifer K
authors.initials: JK
authors.lastname: Pirri
authors.forename: Mark J
authors.initials: MJ
authors.lastname: Alkema
mesh_terms: D000818:Animals; D017173:Caenorhabditis elegans; D007395:Interneurons / Q000378:metabolism*; D008124:Locomotion; D009043:Motor Activity; D009154:Mutation; D015222:Sodium Channels / Q000235:genetics / Q000378:metabolism*; D055366:Synaptic Potentials
chemical_list: D015222:Sodium Channels