Pulsatile insulin secretion into the portal vein from the many pancreatic islets of Langerhans is critical for efficient glucose homeostasis. The islets are themselves endogenous oscillators, but since they are not physically coupled it is not obvious how their oscillations are synchronized across the pancreas. It has been proposed that synchronization of islets is achieved through periodic activity of intrapancreatic ganglia, and indeed there are data supporting this proposal. Postganglionic nerves are cholinergic, and their product, acetylcholine, can influence islet β-cells through actions on M3 muscarinic receptors which are coupled to Gq type G-proteins. In addition, the neurons secrete several peptide hormones that act on β-cell receptors. The data supporting synchronization via intrapancreatic ganglia are, however, limited. In particular, it has not been shown that trains of muscarinic pulses are effective at synchronizing islets in vitro. Also, if as has been suggested, there is a ganglionic pacemaker driving islets to a preferred frequency, no neural circuitry for this pacemaker has been identified. In this study, both points are addressed using a microfluidic system that allows for the pulsed application of the muscarinic agonist carbachol. We find that murine islets are entrained and synchronized over a wide range of frequencies when the carbachol pulsing is periodic, adding support to the hypothesis that ganglia can synchronize islets in vivo. We also find that islet synchronization is very effective even if the carbachol pulses are applied at random times. This suggests that a neural pacemaker is not needed; all that is required is that islets receive occasional coordinated input from postganglionic neurons. The endogenous rhythmic activity of the islets then sets the frequency of the islet population rhythm, while the input from ganglia acts only to keep the islet oscillators in phase.

Drosophila melanogaster (Meigen) (Diptera: Drosophilidae) exhibits several welldefined sleep parameters and a sleep:wake rhythm strength cycle that fragments and deteriorates with age. Because many aspects of functional senescence may be linked to the effects of accumulated oxidative damage, and as several lines of experimental evidence indicate that sleep parameters and sleep:wake rhythm strength may be modulated by oxidative stress in D. melanogaster, it has been postulated that sleep fragmentation is driven, at least in part, by accumulated oxidative damage in this By. We investigated the contrasting effects of an enriched dietary regime that is likely to exacerbate processes associated with aging and oxidative damage accumulation, and a dietary restriction regime that has been demonstrated to delay the detectable effects of aging-related damage on lifelong sleep and activity patterns in male and female D. melanogaster. We found that female fiies on a nutrient-rich dietary regime exhibited stronger sleep:wake cycles than females on a dietary restriction regime and that dietary restriction did not seem to alter the initiation of sleep fragmentation in female or male D. melanogaster.