Neuropeptide dynamics coordinate layered plasticity mechanisms adapting circadian behavior to changing environment.

The brain contains distinct circadian oscillators responsible for generating the morning and evening bouts of locomotor activity in light-dark cycles. We lack a mechanistic understanding of how environmental changes reshape the resulting bimodal rest-activity pattern. Here, we uncover a seasonal switch mechanism that remodels the evening bout of activity.

A single photoreceptor splits perception and entrainment by cotransmission.

Vision enables both image-forming perception, driven by a contrast-based pathway, and unconscious non-image-forming circadian photoentrainment, driven by an irradiance-based pathway. Although two distinct photoreceptor populations are specialized for each visual task, image-forming photoreceptors can additionally contribute to photoentrainment of the circadian clock in different species. However, it is unknown how the image-forming photoreceptor pathway can functionally implement the segregation of irradiance signals required for circadian photoentrainment from contrast signals required for image perception.

Enhanced neuroimaging with a calcium sensor in brains using closed-loop adaptive optics light-sheet fluorescence microscopy.

Significance: Adaptive optics (AO) has been implemented on several microscopy setups and has proven its ability to increase both signal and resolution. However, reported configurations are not suited for fast imaging of live samples or are based on an invasive or complex implementation method.

Aim: Provide a fast aberration correction method with an easy to implement AO module compatible with light-sheet fluorescence microscopy (LSFM) for enhanced imaging of live samples.

Circadian Clocks: Structural Plasticity on the Input Side.

Key Drosophila clock neurons remodel their axonal arborization on a daily basis. The current view is that remodelling is part of the control of clock neuron output but new data support a major role in modulating sensory inputs.

Adaptive optics light-sheet microscopy based on direct wavefront sensing without any guide star.

We propose an adaptive optics light-sheet fluorescence microscope (AO-LSFM) for closed-loop aberrations' correction at the emission path, providing intrinsic instrumental simplicity and high accuracy when compared to previously reported schemes. The approach is based on direct wavefront sensing, i.e.

PERIOD-controlled deadenylation of the transcript in the circadian clock.

The circadian oscillator relies on a negative transcriptional feedback loop, in which the PERIOD (PER) and TIMELESS (TIM) proteins repress the expression of their own gene by inhibiting the activity of the CLOCK (CLK) and CYCLE (CYC) transcription factors. A series of posttranslational modifications contribute to the oscillations of the PER and TIM proteins but few posttranscriptional mechanisms have been described that affect mRNA stability. Here we report that down-regulation of the POP2 deadenylase, a key component of the CCR4-NOT deadenylation complex, alters behavioral rhythms.

The HisCl1 histamine receptor acts in photoreceptors to synchronize Drosophila behavioral rhythms with light-dark cycles.

In Drosophila, the clock that controls rest-activity rhythms synchronizes with light-dark cycles through either the blue-light sensitive cryptochrome (Cry) located in most clock neurons, or rhodopsin-expressing histaminergic photoreceptors. Here we show that, in the absence of Cry, each of the two histamine receptors Ort and HisCl1 contribute to entrain the clock whereas no entrainment occurs in the absence of the two receptors. In contrast to Ort, HisCl1 does not restore entrainment when expressed in the optic lobe interneurons.

Low-intensity electromagnetic fields induce human cryptochrome to modulate intracellular reactive oxygen species.

Exposure to man-made electromagnetic fields (EMFs), which increasingly pollute our environment, have consequences for human health about which there is continuing ignorance and debate. Whereas there is considerable ongoing concern about their harmful effects, magnetic fields are at the same time being applied as therapeutic tools in regenerative medicine, oncology, orthopedics, and neurology. This paradox cannot be resolved until the cellular mechanisms underlying such effects are identified.

Reconfiguration of a Multi-oscillator Network by Light in the Drosophila Circadian Clock.

The brain clock that drives circadian rhythms of locomotor activity relies on a multi-oscillator neuronal network. In addition to synchronizing the clock with day-night cycles, light also reformats the clock-driven daily activity pattern. How changes in lighting conditions modify the contribution of the different oscillators to remodel the daily activity pattern remains largely unknown.

Ubiquitylation Dynamics of the Clock Cell Proteome and TIMELESS during a Circadian Cycle.

Circadian clocks have evolved as time-measuring molecular devices to help organisms adapt their physiology to daily changes in light and temperature. Transcriptional oscillations account for a large fraction of rhythmic protein abundance. However, cycling of various posttranslational modifications, such as ubiquitylation, also contributes to shape the rhythmic protein landscape.

A Statistically Representative Atlas for Mapping Neuronal Circuits in the Adult Brain.

Imaging the expression patterns of reporter constructs is a powerful tool to dissect the neuronal circuits of perception and behavior in the adult brain of , one of the major models for studying brain functions. To date, several brain templates and digital atlases have been built to automatically analyze and compare collections of expression pattern images. However, there has been no systematic comparison of performances between alternative atlasing strategies and registration algorithms.

Four of the six Drosophila rhodopsin-expressing photoreceptors can mediate circadian entrainment in low light.

Light is the major stimulus for the synchronization of circadian clocks with day-night cycles. The light-driven entrainment of the clock that controls rest-activity rhythms in Drosophila relies on different photoreceptive molecules. Cryptochrome (CRY) is expressed in most brain clock neurons, whereas six different rhodopsins (RH) are present in the light-sensing organs.

Clock genes: from Drosophila to humans.

The circadian clock that governs sleep-wake rhythms stems from a small set of genes, called clock genes, that are highly conserved during evolution. In insects as in mammals, a transcriptional feedback loop generates 24 h molecular oscillations. Two major transcrip- tional activators direct the expression of genes encoding repressors the accumulation of which leads afew hours later to transcriptional inhibition.

Daytime CLOCK Dephosphorylation Is Controlled by STRIPAK Complexes in Drosophila.

In the Drosophila circadian oscillator, the CLOCK/CYCLE complex activates transcription of period (per) and timeless (tim) in the evening. PER and TIM proteins then repress CLOCK (CLK) activity during the night. The pace of the oscillator depends upon post-translational regulation that affects both positive and negative components of the transcriptional loop.

The CK2 kinase stabilizes CLOCK and represses its activity in the Drosophila circadian oscillator.

Phosphorylation is a pivotal regulatory mechanism for protein stability and activity in circadian clocks regardless of their evolutionary origin. It determines the speed and strength of molecular oscillations by acting on transcriptional activators and their repressors, which form negative feedback loops. In Drosophila, the CK2 kinase phosphorylates and destabilizes the PERIOD (PER) and TIMELESS (TIM) proteins, which inhibit CLOCK (CLK) transcriptional activity.

CULLIN-3 controls TIMELESS oscillations in the Drosophila circadian clock.

Eukaryotic circadian clocks rely on transcriptional feedback loops. In Drosophila, the PERIOD (PER) and TIMELESS (TIM) proteins accumulate during the night, inhibit the activity of the CLOCK (CLK)/CYCLE (CYC) transcriptional complex, and are degraded in the early morning. The control of PER and TIM oscillations largely depends on post-translational mechanisms.

Human cryptochrome-1 confers light independent biological activity in transgenic Drosophila correlated with flavin radical stability.

Cryptochromes are conserved flavoprotein receptors found throughout the biological kingdom with diversified roles in plant development and entrainment of the circadian clock in animals. Light perception is proposed to occur through flavin radical formation that correlates with biological activity in vivo in both plants and Drosophila. By contrast, mammalian (Type II) cryptochromes regulate the circadian clock independently of light, raising the fundamental question of whether mammalian cryptochromes have evolved entirely distinct signaling mechanisms.

Identifying specific light inputs for each subgroup of brain clock neurons in Drosophila larvae.

In Drosophila, opsin visual photopigments as well as blue-light-sensitive cryptochrome (CRY) contribute to the synchronization of circadian clocks. We focused on the relatively simple larval brain, with nine clock neurons per hemisphere: five lateral neurons (LNs), four of which express the pigment-dispersing factor (PDF) neuropeptide, and two pairs of dorsal neurons (DN1s and DN2s). CRY is present only in the PDF-expressing LNs and the DN1s.

The E3 ubiquitin ligase CTRIP controls CLOCK levels and PERIOD oscillations in Drosophila.

In the Drosophila circadian clock, the CLOCK/CYCLE complex activates the period and timeless genes that negatively feedback on CLOCK/CYCLE activity. The 24-h pace of this cycle depends on the stability of the clock proteins. RING-domain E3 ubiquitin ligases have been shown to destabilize PERIOD or TIMELESS.

PDF-modulated visual inputs and cryptochrome define diurnal behavior in Drosophila.

Morning and evening circadian oscillators control the bimodal activity of Drosophila in light-dark cycles. The lateral neurons evening oscillator (LN-EO) is important for promoting diurnal activity at dusk. We found that the LN-EO autonomously synchronized to light-dark cycles through either the cryptochrome (CRY) that it expressed or the visual system.

Period gene expression in four neurons is sufficient for rhythmic activity of Drosophila melanogaster under dim light conditions.

The clock gene expressing lateral neurons (LN) is crucial for Drosophila 's rhythmic locomotor activity under constant conditions. Among the LN, the PDF expressing small ventral lateral neurons (s-LN(v)) are thought to control the morning activity of the fly (M oscillators) and to drive rhythmic activity under constant darkness. In contrast, a 5th PDF-negative s-LN( v) and the dorsal lateral neurons (LN(d)) appeared to control the fly's evening activity (E oscillators) and to drive rhythmic activity under constant light.