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Animals exhibit rhythmic patterns of behavior that are shaped by an internal circadian clock and the external environment. Although light intensity varies across the day, there are particularly robust differences at twilight (dawn/dusk). These periods are also associated with major changes in behavioral states, such as the transition from arousal to sleep. However, the neural mechanisms by which time and environmental conditions promote these behavioral transitions are poorly defined. Here, we show that the E1 subclass of Drosophila evening clock neurons promotes the transition from arousal to sleep at dusk. We first demonstrate that the cell-autonomous clocks of E2 neurons primarily drive and adjust the phase of evening anticipation, the canonical behavior associated with "evening" clock neurons. We next show that conditionally silencing E1 neurons causes a significant delay in sleep onset after dusk. However, rather than simply promoting sleep, activating E1 neurons produces time- and light-dependent effects on behavior. Activation of E1 neurons has no effect early in the day but then triggers arousal before dusk and induces sleep after dusk. Strikingly, these activation-induced phenotypes depend on the presence of light during the day. Despite their influence on behavior around dusk, in vivo voltage imaging of E1 neurons reveals that their spiking rate and pattern do not significantly change throughout the day. Moreover, E1-specific clock ablation has no effect on arousal or sleep. Thus, we suggest that, rather than specifying "evening" time, E1 neurons act, in concert with other rhythmic neurons, to promote behavioral transitions at dusk., Competing Interests: Declaration of interests The authors declare no competing interests., (Copyright © 2024 Elsevier Inc. All rights reserved.)

Mini-PCNL is one of the most effective surgical methods in the treatment of kidney stones in pediatric patients. In this study, we aimed to compare PCNL in the supine-prone position in pediatric patients (especially operation time, postop complications, hospital stay and stone-free rates).We conducted our study in a randomized and prospective manner. Patients with lower pole stones larger than 1 cm, stones larger than 1.5 cm in the pelvis, upper pole, midpole or multiple locations, and patients who did not respond to ESWL or whose family that preferred mini-PCNL to be the primary treatment were included in the study. Patients with any previous kidney stone surgery, patients with coagulation disorders and patients with retrorenal colon were excluded from the study. Between 2021 and 2023, a total of 144 patients underwent PCNL. 68 of these patients had supine PCNL and 76 prone PCNL. Postoperative Clavien grade1 complication occurred in a total of 7 patients in the prone position; Clavien grade1 complication occurred in 1 patient in the supine position. The mean operation time for prone PCNL was 119.88 ± 28.32 min, and the mean operative time for supine PCNL was 98.12 ± 14.97 the mean hospitalization time in prone PCNL was 3.56 ± 1.12 days, and 3.00 ± 0.85 days in supine PCNL. In conclusion, supine PCNL is a safe and effective method in the treatment of pediatric kidney stones and postoperative complications were observed to be less; the operation time and hospital stay were shorter in supine PCNL., (© 2024. The Author(s).)

Circadian clocks generate rhythms of arousal, but the underlying molecular and cellular mechanisms remain unclear. In Drosophila, the clock output molecule WIDE AWAKE (WAKE) labels rhythmic neural networks and cyclically regulates sleep and arousal. Here, we show, in a male mouse model, that mWAKE/ANKFN1 labels a subpopulation of dorsomedial hypothalamus (DMH) neurons involved in rhythmic arousal and acts in the DMH to reduce arousal at night. In vivo Ca 2+ imaging reveals elevated DMH mWAKE activity during wakefulness and rapid eye movement (REM) sleep, while patch-clamp recordings show that DMH mWAKE neurons fire more frequently at night. Chemogenetic manipulations demonstrate that DMH mWAKE neurons are necessary and sufficient for arousal. Single-cell profiling coupled with optogenetic activation experiments suggest that GABAergic DMH mWAKE neurons promote arousal. Surprisingly, our data suggest that mWAKE acts as a clock-dependent brake on arousal during the night, when mice are normally active. mWAKE levels peak at night under clock control, and loss of mWAKE leads to hyperarousal and greater DMH mWAKE neuronal excitability specifically at night. These results suggest that the clock does not solely promote arousal during an animal's active period, but instead uses opposing processes to produce appropriate levels of arousal in a time-dependent manner., (© 2023. Springer Nature Limited.)

Stereotyped synaptic connections define the neural circuits of the brain. In vertebrates, stimulus-independent activity contributes to neural circuit formation. It is unknown whether this type of activity is a general feature of nervous system development. Here, we report patterned, stimulus-independent neural activity in the Drosophila visual system during synaptogenesis. Using in vivo calcium, voltage, and glutamate imaging, we found that all neurons participate in this spontaneous activity, which is characterized by brain-wide periodic active and silent phases. Glia are active in a complementary pattern. Each of the 15 of over 100 specific neuron types in the fly visual system examined exhibited a unique activity signature. The activity of neurons that are synaptic partners in the adult was highly correlated during development. We propose that this cell-type-specific activity coordinates the development of the functional circuitry of the adult brain., (Copyright © 2019 Elsevier Inc. All rights reserved.)

It is well established that perception is largely multisensory; often served by modalities such as touch, vision, and hearing that detect stimuli emanating from a common point in space; and processed by brain tissue maps that are spatially aligned. However, the neural interactions among modalities that share no spatial stimulus domain yet are essential for robust perception within noisy environments remain uncharacterized. Drosophila melanogaster makes its living navigating food odor plumes. Odor acts to increase the strength of gaze-stabilizing optomotor reflexes to keep the animal aligned within an invisible plume, facilitating odor localization in free flight. Here, we investigate the cellular mechanism for cross-modal behavioral interactions. We characterize a wide-field motion-selective interneuron of the lobula plate that shares anatomical and physiological similarities with the "Hx" neuron identified in larger flies. Drosophila Hx exhibits cross-modal enhancement of visual responses by paired odor, and presynaptic inputs to the lobula plate are required for behavioral odor tracking but are not themselves the target of odor modulation, nor is the neighboring wide-field "HSE" neuron. Octopaminergic neurons mediating increased visual responses upon flight initiation also show odor-evoked calcium modulations and form connections with Hx dendrites. Finally, restoring synaptic vesicle trafficking within the octopaminergic neurons of animals carrying a null mutation for all aminergic signaling is sufficient to restore odor-tracking behavior. These results are the first to demonstrate cellular mechanisms underlying visual-olfactory integration required for odor localization in fruit flies, which may be representative of adaptive multisensory interactions across taxa., (Copyright © 2015 The Authors. Published by Elsevier Ltd.. All rights reserved.)

A moving visual figure may contain first-order signals defined by variation in mean luminance, as well as second-order signals defined by constant mean luminance and variation in luminance envelope, or higher-order signals that cannot be estimated by taking higher moments of the luminance distribution. Separating these properties of a moving figure to experimentally probe the visual subsystems that encode them is technically challenging and has resulted in debated mechanisms of visual object detection by flies. Our prior work took a white noise systems identification approach using a commercially available electronic display system to characterize the spatial variation in the temporal dynamics of two distinct subsystems for first- and higher-order components of visual figure tracking. The method relied on the use of single pixel displacements of two visual stimuli according to two binary maximum length shift register sequences (m-sequences) and cross-correlation of each m-sequence with time-varying flight steering measurements. The resultant spatio-temporal action fields represent temporal impulse responses parameterized by the azimuthal location of the visual figure, one STAF for first-order and another for higher-order components of compound stimuli. Here we review m-sequence and reverse correlation procedures, then describe our application in detail, provide Matlab code, validate the STAFs, and demonstrate the utility and robustness of STAFs by predicting the results of other published experimental procedures. This method has demonstrated how two relatively modest innovations on classical white noise analysis--the inclusion of space as a way to organize response kernels and the use of linear decoupling to measure the response to two channels of visual information simultaneously--could substantially improve our basic understanding of visual processing in the fly.

AMPA-type glutamate receptors mediate fast, excitatory neurotransmission in the brain, and their concentrations at synapses are important determinants of synaptic strength. We investigated the post-transcriptional regulation of GluA2, the calcium-impermeable AMPA receptor subunit, by examining the subcellular distribution of its mRNA and evaluating its translational regulation by microRNA in cultured mouse hippocampal neurons. Using computational approaches, we identified a conserved microRNA-124 (miR-124) binding site in the 3'UTR of GluA2 and demonstrated that miR-124 regulated the translation of GluA2 mRNA reporters in a sequence-specific manner in luciferase assays. While we hypothesized that this regulation might occur in dendrites, our biochemical and fluorescent in situ hybridization (FISH) data indicate that GluA2 mRNA does not localize to dendrites or synapses of mouse hippocampal neurons. In contrast, we detected significant concentrations of miR-124 in dendrites. Overexpression of miR-124 in dissociated neurons results in a 30% knockdown of GluA2 protein, as measured by immunoblot and quantitative immunocytochemistry, without producing any changes in GluA2 mRNA concentrations. While total GluA2 concentrations are reduced, we did not detect any changes in the concentration of synaptic GluA2. We conclude from these results that miR-124 interacts with GluA2 mRNA in the cell body to downregulate translation. Our data support a model in which GluA2 is translated in the cell body and subsequently transported to neuronal dendrites and synapses, and suggest that synaptic GluA2 concentrations are modified primarily by regulated protein trafficking rather than by regulated local translation., (Copyright © 2014 Elsevier Inc. All rights reserved.)