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Abhilash, L.

Publications and source records attributed to Abhilash, L..

6 recordsLinked to original sources

The recognition of behaviorally distinct sleep stages in Drosophila melanogaster uncovers previously obscured homeostatic and circadian control of sleep.

Understanding the mechanisms underlying homeostatic sleep regulation is a central unmet goal of sleep science. Our comprehension of such regulation in mammals has required recognizing distinct sleep stages. Drosophila melanogaster is an important genetic model system for studying sleep. Since the discovery of sleep-like states in the fly 25 years ago, the field has treated sleep as a unitary state consisting of any inactivity lasting 5 minutes or longer, despite convergent work suggesting the existence of multiple sleep states. Here, we establish that three distinct sleep states in flies can be classified based on simple inactivity duration criteria. We show that the daily initiation of these sleep states is temporally distinct, with long sleep occurring immediately following the largest daily period of wakefulness. We also report that rebound in response to mechanical sleep deprivation is present only in long sleep and comes at the expense of shorter sleep states. Deprivation-induced decreases in shorter sleep states obscure homeostatic sleep rebound, but only when sleep is measured using traditional methods. We observe distinctly timed ultradian oscillations of fly sleep states, reminiscent of mammalian sleep cycles. Our results indicate that the recognition of such sleep states will be necessary to fully realize the promise of the Drosophila model system for identifying conserved genetic mechanisms underlying such regulation.

animal behavior and cognition↗

Homeostatic control of deep sleep in Drosophila: Implications for Discovering Correlates of Sleep Pressure

Homeostatic control of sleep is typically addressed through mechanical stimulation-induced forced wakefulness and the measurement of subsequent increases in sleep. A major confound attends this approach: biological responses to deprivation may reflect a direct response to the mechanical insult rather than to the loss of sleep. Similar confounds accompany all forms of sleep deprivation and represent a major challenge to the field. Here we describe a new paradigm for sleep deprivation in Drosophila that fully accounts for sleep-independent effects. Our results reveal that deep sleep states are the primary target of homeostatic control and establish the presence of multi-cycle sleep rebound following deprivation. Furthermore, we establish that specific deprivation of deep sleep state results in state-specific homeostatic rebound. Finally, by accounting for the molecular effects of mechanical stimulation during deprivation experiments, we show that serotonin levels track sleep pressure in the flys central brain. Our results illustrate the critical need to control for sleep-independent effects of deprivation when examining the molecular correlates of sleep pressure and call for a critical reassessment of work that has not accounted for such non-specific effects.

animal behavior and cognition↗

Circadian Regulation of Sleep in Drosophila: Insights from a Two-Process Model

Sleep is controlled by two processes - a circadian clock that regulates its timing and a homeostat that regulates the drive to sleep. Drosophila has been an insightful model for understanding both processes. For four decades, Borbely and Daans two-process model has provided a powerful framework for understanding how circadian and homeostatic processes regulate sleep. However, the field of fly sleep has not employed such a model as a framework for the investigation of sleep. To this end, we have adapted the two-process model to the fly and establish its utility by showing that it can provide empirically testable predictions regarding the circadian and homeostatic control of fly sleep. We show that the ultradian rhythms previously reported for loss-of-function clock mutants are a predictable consequence of a functional sleep homeostat in the absence of a functioning circadian system. We find that a model in which the circadian clock speed and homeostatic rates act without influencing each other provides imprecise predictions regarding how clock speed influences the strength of sleep rhythms and the amount of daily sleep. We also find that quantitatively good fits between empirical values and model predictions were achieved only when clock speeds were positively correlated with rates of decay of sleep pressure. Our results indicate that longer sleep bouts better reflect the homeostatic process than the current definition of sleep as any inactivity lasting five minutes or more. This two-process model represents a powerful framework for future work on the molecular and physiological regulation of fly sleep.

animal behavior and cognition↗

Parametric effects of light acting via multiple photoreceptor types contribute significantly to circadian entrainment in Drosophila melanogaster.

Circadian rhythms in physiology and behavior have near 24-hour periodicities that must adjust to the exact 24-hour geophysical cycles on earth to ensure adaptive daily timing. Such adjustment is called entrainment. One major mode of entrainment is via the continuous modulation of circadian period by the prolonged presence of light. Although Drosophila melanogaster is a prominent insect model of chronobiology, there is little evidence for such continuous effects of light in the species. In this study, we demonstrate that prolonged light exposure at specific times of the day shapes the daily timing of activity in flies. We also establish that continuous blue- and UV-blocked light lengthens the circadian period of Drosophila and provide evidence that this is produced by the combined action of multiple photoreceptors which, includes the cell autonomous photoreceptor cryptochrome. Finally, we introduce ramped light cycles as an entrainment paradigm that produces light entrainment that lacks the large light-driven startle responses typically displayed by flies and requires multiple days for entrainment to shifted cycles. These features are reminiscent of entrainment in mammalian models systems and make possible new experimental approaches to understanding the mechanisms underlying entrainment in the fly.

genetics↗

PHASE: A MATLAB Based Program for the Analysis of Drosophila Phase, Activity, and Sleep under Entrainment

The problem of entrainment is central to circadian biology. In this regard, Drosophila has been an important model system. Owing to the simplicity of its nervous system and the availability of powerful genetic tools, the system has shed significant light on the molecular and neural underpinnings of entrainment. However, much remains to be learned regarding the molecular and physiological mechanisms underlying this important phenomenon. Under cyclic light/dark conditions, Drosophila melanogaster displays crepuscular patterns of locomotor activity with one peak anticipating dawn and the other anticipating dusk. These peaks are characterized through an estimation of their phase relative to the environmental light cycle and the extent of their anticipation of light transitions. In Drosophila chronobiology, estimations of phases are often subjective, and anticipation indices vary significantly between studies. Though there is increasing interest in building flexible analysis software tools in the field, none incorporates objective measures of Drosophila activity peaks in combination with the analysis of fly activity/sleep in the same program. To this end, we have developed PHASE, a MATLAB-based program that is simple and easy to use and (i) supports the visualization and analysis of activity and sleep under entrainment, (ii) allows analysis of both activity and sleep parameters within user-defined windows within a diurnal cycle, (iii) uses a smoothing filter for the objective identification of peaks of activity (and therefore can be used to quantitatively characterize them), and (iv) offers a series of analyses for the assessment of behavioral anticipation of environmental transitions.

animal behavior and cognition↗

Activity/rest rhythms of Drosophila populations selected for divergent eclosion timing under temperature cues

Despite the fact that the rhythm in adult emergence and rhythm in locomotor activity are two different rhythmic phenomena that occur at distinct life-stages of the fly life cycle, previous studies have hinted at similarities in certain aspects of the organisation of the circadian clock driving these two rhythms. In an earlier study, we have shown that selection on timing of adult emergence behaviour in populations of Drosophila melanogaster leads to the co-evolution of temperature sensitivity of circadian clocks driving eclosion. In this study, we were interested in asking if temperature sensitivity of the locomotor activity rhythm has evolved in our populations with divergent timing of adult emergence rhythm, with the goal of understanding the extent of similarity (or lack of it) in circadian organisation between the two rhythms. We found that in response to simulated jetlag with temperature cycles, late chronotypes (populations selected for predominant emergence during dusk) indeed re-entrain faster than early chronotypes (populations selected for predominant emergence during dawn), thereby indicating enhanced sensitivity of the activity/rest clock to temperature cues in these stocks (entrainment is the synchronisation of internal rhythms to cyclic environmental time-cues). Additionally, we found that late chronotypes show higher plasticity of phases across regimes, day-to-day stability in phases and amplitude of entrainment, all indicative of enhanced temperature sensitive activity/rest rhythms. Our results highlight remarkably similar organisation principles between emergence and activity/rest rhythms.

animal behavior and cognition↗