Coordination of rhythmic locomotion depends upon a precisely balanced interplay between central and peripheral control mechanisms. Although poorly understood, peripheral proprioceptive mechanosensory input is thought to provide information about body position for moment-to-moment modifications of central mechanisms mediating rhythmic motor output. Pickpocket1 (PPK1) is a Drosophila subunit of the epithelial sodium channel (ENaC) family displaying limited expression in multiple dendritic (md) sensory neurons tiling the larval body wall and a small number of bipolar neurons in the upper brain. ppk1 null mutant larvae had normal external touch sensation and md neuron morphology but displayed striking alterations in crawling behavior. Loss of PPK1 function caused an increase in crawling speed and an unusual straight path with decreased stops and turns relative to wild-type. This enhanced locomotion resulted from sustained peristaltic contraction wave cycling at higher frequency with a significant decrease in pause period between contraction cycles. The mutant phenotype was rescued by a wild-type PPK1 transgene and duplicated by expressing a ppk1RNAi transgene or a dominant-negative PPK1 isoform. These results demonstrate that the PPK1 channel plays an essential role in controlling rhythmic locomotion and provide a powerful genetic model system for further analysis of central and peripheral control mechanisms and their role in movement disorders.

This study describes, for the first time, the rhythmic translational program within circadian clock cells. The results indicate that most clock cell mRNAs are translated at low-energy times of either mid-day or mid-night, and also that related cellular functions are coordinately regulated by the synchronized translation of relevant mRNAs at the same time of day.

The subcellular localization and translation of mRNA supports functional differentiation between cellular compartments. In neuronal dendrites, local translation of mRNA provides a rapid and specific mechanism for synaptic plasticity and memory formation, and might be involved in the pathophysiology of certain brain disorders. Despite the importance of dendritic mRNA translation, little is known about which mRNAs can be translated in dendrites in vivo and when their translation occurs. Here we collect ribosome-bound mRNA from the dendrites of CA1 pyramidal neurons in the adult mouse hippocampus. We find that dendritic mRNA rapidly associates with ribosomes following a novel experience consisting of a contextual fear conditioning trial. High throughput RNA sequencing followed by machine learning classification reveals an unexpected breadth of ribosome-bound dendritic mRNAs, including mRNAs expected to be entirely somatic. Our findings are in agreement with a mechanism of synaptic plasticity that engages the acute local translation of functionally diverse dendritic mRNAs.

Growth of multicellular organisms proceeds through a series of precisely timed developmental events requiring coordination between gene expression, behavioral changes, and environmental conditions. In Drosophila melanogaster larvae, the essential midthird instar transition from foraging (feeding) to wandering (non-feeding) behavior occurs prior to pupariation and metamorphosis. The timing of this key transition is coordinated with larval growth and size, but physiological mechanisms regulating this process are poorly understood. Results presented here show that Drosophila larvae associate specific environmental conditions, such as temperature, with food in order to enact appropriate foraging strategies. The transition from foraging to wandering behavior is associated with a striking reversal in the behavioral responses to food-associated stimuli that begins early in the third instar, well before food exit. Genetic manipulations disrupting expression of the Degenerin/Epithelial Sodium Channel subunit, Pickpocket1(PPK1) or function of PPK1 peripheral sensory neurons caused defects in the timing of these behavioral transitions. Transient inactivation experiments demonstrated that sensory input from PPK1 neurons is required during a critical period early in the third instar to influence this developmental transition. Results demonstrate a key role for the PPK1 sensory neurons in regulation of important behavioral transitions associated with developmental progression of larvae from foraging to wandering stage.