Disruption of synaptic transmission or clock-gene-product oscillations in circadian pacemaker cells of Drosophila cause abnormal behavioral rhythms.

Jun 8, 2000Journal of neurobiology

Disrupting communication or internal clocks in fruit fly time-keeping cells causes irregular behavior patterns

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Abstract

The proportion of rhythmic Drosophila in constant darkness was reduced when expressing active tetanus-toxin light chain (TeTxLC).

TeTxLC disrupted the rhythmic behavior of adult Drosophila without affecting the gross cycling of clock-gene products.
Flies expressing active TeTxLC were less synchronized to light:dark cycles compared to controls.
Limited expression of TeTxLC in pdf-expressing neurons had little impact on behavioral rhythms, suggesting involvement of other per/tim-expressing neurons.
Increased expression of period gene products disrupted the transcriptional feedback loop essential for circadian rhythms.
Flies with altered PER expression under tim-gal4 exhibited abnormal behavior in light:dark cycles.

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To study the function of clock-gene-expressing neurons, the tetanus-toxin light chain (TeTxLC), which blocks chemical synaptic transmission, was expressed under the control of promoters of the clock genes period (per) and timeless (tim), each fused to GAL4-encoding sequences. Although TeTxLC did not affect cycling of a clock-gene product at the gross level, it disrupted the rhythmic behavior of adult Drosophila. In constant darkness, the proportion of rhythmic flies was reduced in flies expressing active TeTxLC compared to controls, including those expressing inactive toxin. The behavior of TeTxLC-expressing flies was less synchronized to light:dark cycles than that of controls. To determine which neurons are responsible for these effects on behavior, the toxin was also expressed in restricted subsets of per/tim-expressing, laterally located pacemaker neurons by expressing TeTxLC under the control of a driver in which GAL4-encoding sequences are fused to the promoter of the pigment dispersing factor (pdf) gene. pdf-gal4-driven TeTxLC expression had relatively little effect on behavioral rhythms, implying that per/tim neurons other than pdf-expressing lateral neurons participate in the generation of rhythmic behavior. In another set of experiments, period gene products were expressed under the control of per-gal4 or tim-gal4. This resulted in an increased level of PER protein in many brain cells and reduction of bioluminescence cycling reported by a per-luciferase transgene, especially in the case of per expression affected by tim-gal4. This indicates a disruption of the transcriptional feedback loop that is a part of the oscillatory mechanism underlying Drosophila's circadian rhythms. Consistent with this molecular defect, the proportion of rhythmic individuals in constant darkness was subnormal in flies expressing PER under the control of tim-gal4, and their behavior in light:dark cycles was abnormal.

Disruption of synaptic transmission or clock-gene-product oscillations in circadian pacemaker cells of Drosophila cause abnormal behavioral rhythms.

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