Circadian rhythms in the morphology of neurons in Drosophila.

Neurons have an enormous capacity to adapt to changing conditions through the regulation of gene expression, morphology, and physiology. In the fruit fly Drosophila melanogaster, this plasticity includes recurrent changes taking place within intervals of a few hours during the day. The rhythmic alterations in the morphology of neurons described so far include changes in axonal diameter, branching complexity, synapse numbers, and the number of synaptic vesicles. The cycles of these changes have larger amplitude when the fly is exposed to light, but they persist in constant darkness and require the expression of the clock genes period and timeless, leading to the concept of circadian plasticity. The molecular mechanisms driving these cycles appear to require the expression of these genes either inside the neurons themselves or in other peripheral pacemaker cells. Loss-of-function mutations in period and timeless not only abolish the morphological rhythms, but also often cause abnormal axonal branching suggesting that circadian plasticity is relevant for the maintenance of normal morphology. Research into whether (1) circadian plasticity is a common feature of neurons in all animals and (2) our own neurons change shape between day and night will be of interest.

A peripheral pacemaker drives the circadian rhythm of synaptic boutons in Drosophila independently of synaptic activity.

Circadian rhythms in the morphology of neurons have been demonstrated in the fly Drosophila melanogaster. One such rhythm is characterized by changes in the size of synaptic boutons of an identified flight motor neuron, with larger boutons during the day compared with those at night. A more detailed temporal resolution of this rhythm shows here that boutons grow at a time of increased locomotor activity during the morning but become gradually smaller during the day and second period of increased locomotor activity in the evening. We have experimentally manipulated the synaptic activity of the fly during short periods of the day to investigate whether changes in bouton size might be a consequence of the different levels of synaptic activity associated with the locomotion rhythm of the fly. In the late night and early morning, when the flies normally have an intense period of locomotion, the boutons grow independently of whether the flies are active or completely paralyzed. Bouton size is not affected by sleep-deprivation during the early night. The cycle in bouton size persists for 2 days even in decapitated flies, which do not move, reinforcing the notion that it is largely independent of synaptic activity, and showing that a pacemaker other than the main biological clock can drive it.

Circadian changes in Drosophila motor terminals.

In Drosophila melanogaster, as in most other higher organisms, a circadian clock controls the rhythmic distribution of rest/sleep and locomotor activity. Here we report that the morphology of Drosophila flight neuromuscular terminals changes between day and night, with a rhythm in synaptic bouton size that continues in constant darkness, but is abolished during aging. Furthermore, arrhythmic mutations in the clock genes timeless and period also disrupt this circadian rhythm. Finally, these clock mutants also have an opposing effect on the nonrhythmic phenotype of neuronal branching, with tim mutants showing a dramatic hyperbranching morphology and per mutants having fewer branches than wild-type flies. These unexpected results reveal further circadian as well as nonclock related pleiotropic effects for these classic behavioral mutants.