Search bioRxiv⌕ Search

Biology subjects

Frenkel, L.

Publications and source records attributed to Frenkel, L..

2 recordsLinked to original sources

High frequency neuronal bursting is essential for circadian and sleep behaviors in Drosophila

Circadian rhythms have been extensively studied in Drosophila, however, still little is known about how the electrical properties of clock neurons are specified. We have performed a behavioral genetic screen through the downregulation of candidate ion channels in the lateral ventral neurons (LNvs) and show that the hyperpolarization-activated cation current Ih is important for the behaviors that the LNvs command: temporal organization of locomotor activity and sleep. Using whole-cell patch clamp electrophysiology we demonstrate that small LNvs are bursting neurons, and that Ih is necessary to achieve the high frequency bursting firing pattern characteristic of both types of LNvs. Since firing in bursts has been associated to neuropeptide release, we hypothesized that Ih would be important for LNvs communication. Indeed, herein we demonstrate that Ih is fundamental for the recruitment of PDF filled dense core vesicles to the terminals at the dorsal protocerebrum and for their timed release, and hence for the temporal coordination of circadian behaviors.

neuroscience↗

Plasma Membrane Calcium Atpase downregulation in dopaminergic neurons alters cellular physiology and behavior in Drosophila melanogaster

Accumulation of calcium is proposed to account for selective dopaminergic neuron (DN) dysfunctionality, a characteristic of Parkinsons Disease (PD). To test the in vivo impact of calcium increment in DN physiology we downregulated the Plasma Membrane Calcium ATPase (PMCA), a bomb that extrudes cytosolic calcium, in those neurons in Drosophila melanogaster. Using th-GAL4>PMCARNAi, PMCA was selectively reduced, leading to increased cytosolic calcium and mitochondrial oxidative stress with no neurodegeneration. In the eye, PMCARNAi expression provoked a subtle disorganization, suggesting scarce toxicity. Interestingly, we observed several locomotor alterations and a higher level of dopamine in brains. Finally, flies presented a reduction of lifespan and a perimortem non-motor phenotype characterized by abdominal swelling, possibly due to constipation. We conclude that elevated cytosolic calcium in DN could trigger cellular dysfunction generating mitochondrial oxidative stress and motor and non-motor symptoms, typical of PD.

neuroscience↗