AbstractInhibition plays important roles in modulating the neural activities of sensory and motor systems at different levels from synapses to brain regions. To achieve coordinated movement, motor systems produce alternating contraction of antagonist muscles, whether along the body axis or within and among limbs. In the nematode C. elegans, a small network involving excitatory cholinergic and inhibitory GABAergic motoneurons generates the dorsoventral alternation of body-wall muscles that supports undulatory locomotion. Inhibition has been suggested to be necessary for backward undulation because mutants that are defective in GABA transmission exhibit a shrinking phenotype in response to a harsh touch to the head, whereas wild-type animals produce a backward escape response. Here, we demonstrate that the shrinking phenotype is exhibited by wild-type as well as mutant animals in response to harsh touch to the head or tail, but only GABA transmission mutants show slow locomotion after stimulation. Impairment of GABA transmission, either genetically or optogenetically, induces lower undulation frequency and lower translocation speed during crawling and swimming in both directions. The activity patterns of GABAergic motoneurons are different during low and high undulation frequencies. During low undulation frequency, GABAergic VD and DD motoneurons show similar activity patterns, while during high undulation frequency, their activity alternates. The experimental results suggest at least three non-mutually exclusive roles for inhibition that could underlie fast undulatory locomotion in C. elegans, which we tested with computational models: cross-inhibition or disinhibition of body-wall muscles, or inhibitory reset.Significance StatementInhibition serves multiple roles in the generation, maintenance, and modulation of the locomotive program and supports the alternating activation of antagonistic muscles. When the locomotor frequency increases, more inhibition is required. To better understand the role of inhibition in locomotion, we used C. elegans as an animal model, and challenged a prevalent hypothesis that cross-inhibition supports the dorsoventral alternation. We find that inhibition is related to the speed rather than the direction of locomotion and demonstrate that inhibition is unnecessary for muscle alternation during slow undulation in either direction but crucial to sustain rapid dorsoventral alternation. We combined calcium imaging of motoneurons and muscle with computational models to test hypotheses for the role of inhibition in locomotion.
Fission and PINK-1-mediated mitophagy are required for Insulin/IGF-1 signaling mutant reproductive longevity
