Biology subjects

Lamaze, A.

Publications and source records attributed to Lamaze, A..

6 recordsLinked to original sources

bioRxiv2021

Nuclear Export of Drosophila PERIOD contributes to temperature compensation of the circadian clock

Circadian clocks are self-sustained molecular oscillators controlling daily changes of behavioral activity and physiology. For functional reliability and precision the frequency of these molecular oscillations must be stable at different environmental temperatures, known as temperature compensation. Despite being an intrinsic property of all circadian clocks, this phenomenon is not well understood at the molecular level. Here we use behavioral and molecular approaches to characterize a novel mutation in the period (per) clock gene of Drosophila melanogaster, which alters a predicted nuclear export sequence (NES) of the PER protein. We show that this new perI530A allele leads to progressively longer behavioral periods and clock oscillations with increasing temperature in both clock neurons and peripheral clock cells. While the mutant PERI530A protein shows normal circadian fluctuations and post-translational modifications at cool temperatures, increasing temperatures lead to both, severe amplitude dampening and hypophosphorylation of PERI530A. We further show that PERI530A displays reduced repressor activity at warmer temperatures, presumably because it cannot inactivate the transcription factor CLOCK (CLK). With increasing temperatures nuclear accumulation of PERI530A within clock neurons is increased, suggesting that PER is normally exported out of the nucleus at warm temperatures. Consequently, downregulating the nuclear export factor CRM1 also leads to temperature-dependent changes of behavioral rhythms. In summary, our results suggest that the PER NES and the nuclear export of clock proteins play an important role in temperature compensation of the Drosophila circadian clock.

neuroscience↗

bioRxiv2020

Circadian clock neurons maintain phase control over daily behavioral activity patterns under divers environmental conditions

Proper timing of rhythmic locomotor behavior is the consequence of integrating environmental conditions and internal time within the circadian clock. The 150 clock neurons in the Drosophila melanogaster brain are organized in various clusters, controlling different aspects of the daily activity rhythms. For example, during regular 12 hr light : 12 hr dark cycles at constant temperature (LD), so called Morning (M) neurons control the activity peak in the morning, while Evening (E-) neurons regulate the activity increase at the end of the day. During the remaining times of day and night, flies are inactive, giving rise to the crepuscular behavior observed in LD. Here, we investigate if the same neuronal groups also control behavioral activity under very different environmental conditions of constant light and temperature cycles (LLTC). While the morning activity is completely absent in LLTC, a single pronounced activity peak occurs at the end of the thermophase. We show that the same E-neurons operating in LD, also regulate the evening peak in LLTC. Interestingly, neuronal activity of E-neurons is inversely correlated with behavioral activity, suggesting an inhibitory action on locomotion. Surprisingly, the E-cells responsible for synchronization to temperature cycles belong to the clock neurons containing the circadian photoreceptor Cryptochrome, previously suggested to be more important for synchronization to LD. Our results therefore support a more deterministic function of the different clock neuronal subgroups, independent of specific environmental conditions. Significance statementMaster circadian clocks in the brains of mammals and fruit fly are composed of neurons expressing varying types of neuropeptides and transmitters. This diversity along with anatomical differences indicate diverse functions of different clock neurons. In Drosophila, so-called Morning (M) and Evening (E) neurons control locomotor activity at the respective time of day during normal day/night (LD) cycles. Recent reports point to a certain degree of plasticity with regard to circadian clock neuron function, depending on specific environmental conditions. Here we show that one neuronal group, the E-neurons, instead behave as if hard-wired to their output targets. Surprisingly they direct activity to occur during the evening both under LD conditions, as well as during temperature cycles in constant light.

neuroscience↗

bioRxiv2019

Antagonistic Regulation of Circadian Output and Synaptic Development by the E3 Ubiquitin Ligase JETLAG and the DYSCHRONIC-SLOWPOKE Complex

Circadian output genes act downstream of the clock to promote rhythmic changes in behavior and physiology, yet their molecular and cellular functions are not well understood. Here we characterize an interaction between regulators of circadian entrainment, output and synaptic development in Drosophila that influences clock-driven anticipatory increases in morning and evening activity. We previously showed the JETLAG (JET) E3 Ubiquitin ligase resets the clock upon light exposure, while the PDZ protein DYSCHRONIC (DYSC) regulates circadian locomotor output and synaptic development. Surprisingly, we find that JET and DYSC antagonistically regulate synaptic development at the larval neuromuscular junction, and reduced JET activity rescues arrhythmicity of dysc mutants. Consistent with our prior finding that DYSC regulates SLOWPOKE (SLO) potassium channel expression, jet mutations also rescue circadian and synaptic phenotypes in slo mutants. Collectively, our data suggest that JET, DYSC and SLO promote circadian output in part by regulating synaptic morphology.\n\nHighlightsO_LILoss of DYSC differentially impacts morning and evening oscillators\nC_LIO_LIReduced JET activity rescues the dysc and slo arrhythmic phenotype\nC_LIO_LIReduced JET activity causes synaptic defects at the larval NMJ\nC_LIO_LIJET opposes DYSC and SLO function at the NMJ synapse\nC_LI

neuroscience↗

bioRxiv2018

A sleep-regulatory circuit integrating circadian, homeostatic and environmental information in Drosophila

In the wild, when to go to sleep is a critical decision. Sleep onset is controlled by two processes: the circadian clock, and a homeostat measuring sleep drive [1, 2]. Environmental stimuli must also clearly intersect with the circadian clock and/or homeostat so that sleep is initiated only when appropriate. Yet how circadian, homeostatic and environmental cues are integrated at the circuit level is unclear. Recently, we found that DN1p clock neurons in Drosophila act to prolong morning wakefulness at elevated ambient temperatures [3]. Here we show that a subset of DN1p neurons exhibit temperature-sensitive increases in excitability, and define an output pathway linking DN1p neurons to downstream sleep-regulatory circuits. We show that DN1p neurons project axons to a subdomain of the Anterior Optic Tubercle (AOTU), and here make inhibitory synaptic connections with sleep-promoting tubercular-bulbar (TuBu) neurons. Using unbiased trans-synaptic labeling, we show that these TuBu neurons form synaptic connections with R-neurons innervating the ellipsoid body, subsets of which control homeostatic sleep drive [4]. DN1p excitability is clock-dependent, peaking in the late night and early morning [5]. Thus, integration of circadian and thermo-sensory information by DN1p neurons and subsequent inhibition of sleep-promoting TuBu neurons provides a mechanism by which an environmental stimulus can regulate sleep onset during a specific compartment of the day-night cycle. Furthermore, our results suggest that the AOTU functionally links circadian and sleep homeostat circuits in Drosophila.

neuroscience↗

bioRxiv2017

Neurocalcin acts in a clock- and light-modulated dopaminergic pathway to promote night sleep in Drosophila

Primary dystonia is a hyperkinetic movement disorder linked to altered dopaminergic signaling and synaptic plasticity in regions of the brain involved in motor control. Mutations in HPCA, encoding the neuronal calcium sensor Hippocalcin, are associated with primary dystonia, suggesting a function for Hippocalcin in regulating the initiation and/or maintenance of activity. However, such a role for Hippocalcin or Hippocalcin homologs has yet to be demonstrated in vivo. Here we investigate the cellular and organismal functions of the Drosophila Hippocalcin homolog Neurocalcin (NCA), and define a role for NCA in promoting sleep by suppressing nighttime hyperactivity. We show that NCA acts in a common pathway with the D1-type Dop1R1 dopamine receptor and facilitates sleep by inhibiting neurotransmitter release from a multi-component activity-promoting circuit. Our results suggest conserved roles for Hippocalcin homologs in modulating motor control through dopaminergic pathways, suppressing aberrant movements in humans and inappropriate nighttime locomotion in Drosophila.

neuroscience↗

bioRxiv2016

Regulation of sleep plasticity by a thermo-sensitive circuit in Drosophila

Sleep is a highly conserved and essential behaviour in many species, including the fruit fly Drosophila melanogaster. In the wild, sensory signalling encoding environmental information must be integrated with sleep drive to ensure that sleep is not initiated during detrimental conditions. However, the molecular and circuit mechanisms by which sleep timing is modulated by the environment are unclear. Here we introduce a novel behavioural paradigm to study this issue. We show that in male fruit flies, onset of the daytime siesta is delayed by ambient temperatures above 29{degrees}C. We term this effect Prolonged Morning Wakefulness (PMW). We show that signalling through the TrpA1 thermo-sensor is required for PMW, and that TrpA1 specifically impacts siesta onset, but not night sleep onset, in response to elevated temperatures. We identify two critical TrpA1-expressing circuits and show that both contact DN1p clock neurons, the output of which is also required for PMW. Finally, we identify the circadian blue-light photoreceptor CRYPTOCHROME as a molecular regulator of PMW. We propose a model in which the Drosophila nervous system integrates information encoding temperature, light, and time to dynamically control when sleep is initiated. Our results provide a platform to investigate how environmental inputs co-ordinately regulate sleep plasticity.

neuroscience↗