scholarly journals Molecular and circuit mechanisms mediating circadian clock output in the Drosophila brain

2018 ◽  
Vol 51 (1) ◽  
pp. 268-281 ◽  
Author(s):  
Anna N. King ◽  
Amita Sehgal
Keyword(s):  
Circadian Clock ◽  
Drosophila Brain ◽  
Circadian Clock Output

scholarly journals Regulation of olfactory associative memory by the circadian clock output signal Pigment-dispersing factor (PDF)

2020 ◽  
Author(s):  
Johanna G. Flyer-Adams ◽  
Emmanuel J. Rivera-Rodriguez ◽  
Jacob D. Mardovin ◽  
Junwei Yu ◽  
Leslie C. Griffith
Keyword(s):  
Circadian Clock ◽  
Associative Memory ◽  
Short Term Memory ◽  
Internal Clock ◽  
Time Of Day ◽  
Memory Formation ◽  
Pigment Dispersing Factor ◽  
Odor Memory ◽  
Circadian Clock Output ◽  
Circuit Output

ABSTRACTDissociation between the output of the circadian clock and external environmental cues is a major cause of human cognitive dysfunction. While the effects of ablation of the molecular clock on memory have been studied in many systems, little has been done to test the role of specific clock circuit output signals. To address this gap, we examined the effects of mutation of Pigment-dispersing factor (Pdf) and its receptor, Pdfr on associative memory in male and female Drosophila. Loss of PDF signaling significantly decreases the ability to form associative memory. Appetitive short-term memory (STM), which in wildtype is time-of-day (TOD)-independent, is decreased across the day by mutation of Pdf or Pdfr, but more substantially in the morning than in the evening. This defect is due to PDFR expression in adult neurons outside the core clock circuit and the mushroom body Kenyon cells. The acquisition of a TOD difference in mutants implies the existence of multiple oscillators that act to normalize memory formation across the day for appetitive processes. Interestingly, aversive STM requires PDF but not PDFR, suggesting that there are valence-specific pathways downstream of PDF that regulate memory formation. These data argue that the circadian clock uses circuit-specific and molecularly diverse output pathways to enhance the ability of animals to optimize responses to changing conditions.SIGNIFICANCE STATEMENTFrom humans to invertebrates, cognitive processes are influenced by organisms’ internal circadian clocks, the pace of which is linked to the solar cycle. Disruption of this link is increasingly common (e.g. jetlag, social jetlag disorders) and causes cognitive impairments that are costly and long-lasting. A detailed understanding of how the internal clock regulates cognition is critical for the development of therapeutic methods. Here, we show for the first time that olfactory associative memory in Drosophila requires signaling by Pigment-dispersing factor (PDF), a neuromodulatory signaling peptide produced only by circadian clock circuit neurons. We also find a novel role for the clock circuit in stabilizing appetitive sucrose/odor memory across the day.

The Paralogous Krüppel-like Factors 9 and 13 Regulate the Mammalian Cellular Circadian Clock Output Gene Dbp

2020 ◽  
Vol 35 (3) ◽  
pp. 257-274 ◽  
Author(s):  
Joseph R. Knoedler ◽  
José Ávila-Mendoza ◽  
Arasakumar Subramani ◽  
Robert J. Denver
Keyword(s):  
Circadian Clock ◽  
Transcriptional Activation ◽  
Mutational Analysis ◽  
Direct Interaction ◽  
Circadian Oscillation ◽  
Ht22 Cells ◽  
The Core ◽  
Mouse Hippocampus ◽  
E Boxes ◽  
Circadian Clock Output

An intricate transcription-translation feedback loop (TTFL) governs cellular circadian rhythms in mammals. Here, we report that the zinc finger transcription factor Krüppel-like factor 9 (KLF9) is regulated by this TTFL, it associates in chromatin at the core circadian clock and clock-output genes, and it acts to modulate transcription of the clock-output gene Dbp. Our earlier genome-wide analysis of the mouse hippocampus-derived cell line HT22 showed that KLF9 associates in chromatin with Per1, Per3, Dbp, Tef, Bhlhe40, Bhlhe41, Nr1d1, and Nr1d2. Of the 3514 KLF9 peaks identified in HT22 cells, 1028 contain E-box sequences to which the transcriptional activators CLOCK and BMAL1 may bind, a frequency significantly greater than expected by chance. Klf9 mRNA showed circadian oscillation in synchronized HT22 cells, mouse hippocampus, and liver. At the clock-output gene Dbp, KLF9 exhibited circadian rhythmicity in its association in chromatin in HT22 cells and hippocampus. Forced expression of KLF9 in HT22 cells repressed basal Dbp transcription and strongly inhibited CLOCK+BMAL1-dependent transcriptional activation of a transfected Dbp reporter. Mutational analysis showed that this action of KLF9 depended on 2 intact KLF9-binding motifs within the Dbp locus that are in close proximity to E-boxes. Knockout of Klf9 or the paralogous gene Klf13 using CRISPR/Cas9 genome editing in HT22 cells had no effect on Dbp expression, but combined knockout of both genes strongly impaired circadian Dbp mRNA oscillation. Like KLF9, KLF13 also showed association in chromatin with clock- and clock-output genes, and forced expression of KLF13 inhibited the actions of CLOCK+BMAL1 on Dbp transcription. Our results suggest novel and partly overlapping roles for KLF9 and KLF13 in modulating cellular circadian clock output by a mechanism involving direct interaction with the core TTFL.

scholarly journals Larval optic nerve and adult extra-retinal photoreceptors sequentially associate with clock neurons during Drosophila brain development

Development ◽  
2002 ◽  
Vol 129 (6) ◽  
pp. 1443-1453 ◽  
Author(s):  
Sébastien Malpel ◽  
André Klarsfeld ◽  
François Rouyer
Keyword(s):  
Optic Nerve ◽  
Visual System ◽  
Circadian Clock ◽  
Brain Development ◽  
Dendritic Morphology ◽  
Retinal Photoreceptors ◽  
Severe Reduction ◽  
Drosophila Brain ◽  
Light Input ◽  
Lateral Neurons

The visual system is one of the input pathways for light into the circadian clock of the Drosophila brain. In particular, extra-retinal visual structures have been proposed to play a role in both larval and adult circadian photoreception. We have analyzed the interactions between extra-retinal structures of the visual system and the clock neurons during brain development. We first show that the larval optic nerve, or Bolwig nerve, already contacts clock cells (the lateral neurons) in the embryonic brain. Analysis of visual system-defective genotypes showed that the absence of the afferent Bolwig nerve resulted in a severe reduction of the lateral neurons dendritic arborization, and that the inhibition of nerve activity induced alterations of the dendritic morphology. During wild-type development, the loss of a functional Bolwig nerve in the early pupa was also accompanied by remodeling of the arborization of the lateral neurons. Approximately 1.5 days later, visual fibers that came from the Hofbauer-Buchner eyelet, a putative photoreceptive organ for the adult circadian clock, were seen contacting the lateral neurons. Both types of extra-retinal photoreceptors expressed rhodopsins RH5 and RH6, as well as the norpA-encoded phospholipase C. These data strongly suggest a role for RH5 and RH6, as well as NORPA, signaling in both larval and adult extra-retinal circadian photoreception. The Hofbauer-Buchner eyelet therefore does not appear to account for the previously described norpA-independent light input to the adult clock. This supports the existence of yet uncharacterized photoreceptive structures in Drosophila.

scholarly journals Oscillating molecules and circadian clock output mechanisms

1998 ◽  
Vol 3 (5) ◽  
pp. 381-385 ◽  
Author(s):  
F R Jackson ◽  
X Zhang ◽  
G P McNeil
Keyword(s):  
Circadian Clock ◽  
Circadian Clock Output

scholarly journals USP2-45 Is a Circadian Clock Output Effector Regulating Calcium Absorption at the Post-Translational Level

PLoS ONE ◽  
2016 ◽  
Vol 11 (1) ◽  
pp. e0145155 ◽  
Author(s):  
Daniel Pouly ◽  
Sébastien Chenaux ◽  
Virginie Martin ◽  
Maja Babis ◽  
Rafael Koch ◽  
...  
Keyword(s):  
Circadian Clock ◽  
Calcium Absorption ◽  
Circadian Clock Output ◽  
Translational Level

scholarly journals Genetic loci mediating circadian clock output plasticity and crop productivity under barley domestication.

2021 ◽  
Author(s):  
Manas R. Prusty ◽  
Eyal Bdolach ◽  
Eiji Yamamoto ◽  
Lalit D. Tiwari ◽  
Roi Silberman ◽  
...  
Keyword(s):  
Circadian Clock ◽  
Crop Productivity ◽  
Genetic Loci ◽  
Circadian Clock Output ◽  
Barley Domestication

scholarly journals A Molecular Rhythm Mediating Circadian Clock Output in Drosophila

Neuron ◽  
1998 ◽  
Vol 20 (2) ◽  
pp. 297-303 ◽  
Author(s):  
Gerard P McNeil ◽  
Xiaolan Zhang ◽  
Ginka Genova ◽  
F.Rob Jackson
Keyword(s):  
Circadian Clock ◽  
Circadian Clock Output
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