Browsing by keyword "Circadian rhythms"
Now showing items 1-4 of 4
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Cell-type specific circadian bioluminescence rhythms recorded from Dbp reporter mice reveal circadian oscillator misalignment [preprint]Circadian rhythms are endogenously generated physiological and molecular rhythms with a cycle length of about 24 h. Bioluminescent reporters have been exceptionally useful for studying circadian rhythms in numerous species. Here, we report development of a reporter mouse generated by modification of a widely expressed and highly rhythmic gene encoding D-site albumin promoter binding protein (Dbp). In this line of mice, firefly luciferase is expressed from the Dbp locus in a Cre-recombinase- dependent manner, allowing assessment of bioluminescence rhythms in specific cellular populations. A mouse line in which luciferase expression was Cre-independent was also generated. The Dbp reporter alleles do not alter Dbp gene expression rhythms in liver or circadian locomotor activity rhythms. In vitro and in vivo studies show the utility of the reporter alleles for monitoring rhythmicity. Our studies reveal cell-type specific characteristics of rhythms among neuronal populations within the suprachiasmatic nuclei in vitro. In vivo studies show stable Dbp-driven bioluminescence rhythms in the liver of Albumin-Cre;DbpKI/+ “liver reporter” mice. After a shift of the lighting schedule, locomotor activity achieved the proper phase relationship with the new lighting cycle more rapidly than hepatic bioluminescence did. As previously shown, restricting food access to the daytime altered the phase of hepatic rhythmicity. Our model allowed assessment of the rate of recovery from misalignment once animals were provided with food ad libitum. These studies provide clear evidence for circadian misalignment following environmental perturbations and reveal the utility of this model for minimally invasive, longitudinal monitoring of rhythmicity from specific mouse tissues.
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Classification and prediction of post-trauma outcomes related to PTSD using circadian rhythm changes measured via wrist-worn research watch in a large longitudinal cohortPost-Traumatic Stress Disorder (PTSD) is a psychiatric condition resulting from threatening or horrifying events. We hypothesized that circadian rhythm changes, measured by a wrist-worn research watch are predictive of post-trauma outcomes. APPROACH: 1618 post-trauma patients were enrolled after admission to emergency departments (ED). Three standardized questionnaires were administered at week eight to measure post-trauma outcomes related to PTSD, sleep disturbance, and pain interference with daily life. Pulse activity and movement data were captured from a research watch for eight weeks. Standard and novel movement and cardiovascular metrics that reflect circadian rhythms were derived using this data. These features were used to train different classifiers to predict the three outcomes derived from week-eight surveys. Clinical surveys administered at ED were also used as features in the baseline models. RESULTS: The highest cross-validated performance of research watch-based features was achieved for classifying participants with pain interference by a logistic regression model, with an area under the receiver operating characteristic curve (AUC) of 0.70. The ED survey-based model achieved an AUC of 0.77, and the fusion of research watch and ED survey metrics improved the AUC to 0.79. SIGNIFICANCE: This work represents the first attempt to predict and classify post-trauma symptoms from passive wearable data using machine learning approaches that leverage the circadian desynchrony in a potential PTSD population.
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Neuronal circuitry controlling circadian photoreception in DrosophilaCircadian clocks are endogenous timekeeping mechanisms, which give the sense of time-of-day to most organisms. To help the organisms to adapt to daily fluctuations in the environment, circadian clocks are reset by various environmental cues. Light is one of the cardinal environmental cues that synchronize circadian clocks. In a standard 12:12 light-dark condition, Drosophila exhibits bimodal activity pattern in the anticipation of lights-on and -off. The morning peak of activity is generated by Pigment Dispersing Factor (PDF) positive small ventro-lateral neurons (sLNvs) called the M-oscillators, while the evening peak of activity is generated by the dorsolateral neurons (LNds) and the 5th sLNv together referred to as the E-oscillators. Since the Drosophila circadian clock is extremely sensitive to light, a brief light exposure can robustly shift the phase of circadian behavior. The model for this resetting posits that circadian photoreception is cell-autonomous: the photoreceptor CRYPTOCHROME (CRY) senses light, binds to TIMELESS (TIM) and promotes its degradation via JETLAG (JET). However, it was more recently proposed that interactions between circadian neurons are also required for phase resetting. The goal of my thesis was to map the neuronal circuitry controlling circadian photoreception in Drosophila. In the first half of my dissertation (Chapter II), using a novel severe jetset mutant and JET RNAi, we identified M- and E-oscillators as critical light sensing neurons. We also found that JET functions cell-autonomously to promote TIM degradation in M- and E-oscillators, and non-autonomously in E-oscillators when expressed in M-oscillators. However, JET expression was required in both groups of neurons to phase-shift locomotor rhythms in response to light input. Thus M- and E-oscillators cooperate to shift circadian behavior in response to photic cues. In chapter III, unexpectedly, we found that light can delay or advance circadian behavior even when the M- or E-oscillators are genetically ablated or incapacitated suggesting that behavioral phase shifts in response to light are largely a consequence of cell autonomous light detection by CRY and governed by the molecular properties of the pacemaker. Nevertheless, neural interactions are integral in modulating light responses. The M-oscillator neurotransmitter, PDF was important in coordinating M- and E-oscillators for circadian behavioral response to light input. Moreover, we uncover a potential role for a subset of Dorsal neurons in control of phase advances specifically. Hence, neural modulation of cell autonomous light detection contributes to plasticity of circadian behavior and facilitates its adaptation to environmental inputs.
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Studying circadian rhythms in Drosophila melanogasterCircadian rhythms have a profound influence on most bodily functions: from metabolism to complex behaviors. They ensure that all these biological processes are optimized with the time-of-day. They are generated by endogenous molecular oscillators that have a period that closely, but not exactly, matches day length. These molecular clocks are synchronized by environmental cycles such as light intensity and temperature. Drosophila melanogaster has been a model organism of choice to understand genetically, molecularly and at the level of neural circuits how circadian rhythms are generated, how they are synchronized by environmental cues, and how they drive behavioral cycles such as locomotor rhythms. This review will cover a wide range of techniques that have been instrumental to our understanding of Drosophila circadian rhythms, and that are essential for current and future research.
