Excitatory motor neurons are local oscillators for backward locomotion.

Cell- or network-driven oscillators underlie motor rhythmicity. The identity of C. elegans oscillators remains unknown. Through cell ablation, electrophysiology, and calcium imaging, we show: (1) forward and backward locomotion is driven by different oscillators; (2) the cholinergic and excitatory A-class motor neurons exhibit intrinsic and oscillatory activity that is sufficient to drive backward locomotion in the absence of premotor interneurons; (3) the UNC-2 P/Q/N high-voltage-activated calcium current underlies A motor neuron's oscillation; (4) descending premotor interneurons AVA, via an evolutionarily conserved, mixed gap junction and chemical synapse configuration, exert state-dependent inhibition and potentiation of A motor neuron's intrinsic activity to regulate backward locomotion. Thus, motor neurons themselves derive rhythms, which are dually regulated by the descending interneurons to control the reversal motor state. These and previous findings exemplify compression: essential circuit properties are conserved but executed by fewer numbers and layers of neurons in a small locomotor network.

NLF-1 delivers a sodium leak channel to regulate neuronal excitability and modulate rhythmic locomotion.

A cation channel NCA/UNC-79/UNC-80 affects neuronal activity. We report here the identification of a conserved endoplasmic reticulum protein NLF-1 (NCA localization factor-1) that regulates neuronal excitability and locomotion through the NCA channel. In C. elegans, the loss of either NLF-1 or NCA leads to a reduced sodium leak current, and a hyperpolarized resting membrane potential in premotor interneurons. This results in a decreased premotor interneuron activity that reduces the initiation and sustainability of rhythmic locomotion. NLF-1 promotes axonal localization of all NCA reporters. Its mouse homolog mNLF-1 functionally substitutes for NLF-1 in C. elegans, interacts with the mammalian sodium leak channel NALCN in vitro, and potentiates sodium leak currents in primary cortical neuron cultures. Taken together, an ER protein NLF-1 delivers a sodium leak channel to maintain neuronal excitability and potentiates a premotor interneuron network critical for C. elegans rhythmic locomotion.