Locomotor Rhythm Research Articles

An intact pituitary vasopressin system is critical for building a robust circadian clock in the suprachiasmatic nucleus

The circadian clock is a biological timekeeping system that oscillates with a circa-24-h period, reset by environmental timing cues, especially light, to the 24-h day-night cycle. In mammals, a "central" clock in the hypothalamic suprachiasmatic nucleus (SCN) synchronizes "peripheral" clocks throughout the body to regulate behavior, metabolism, and physiology. A key feature of the clock's oscillation is resistance to abrupt perturbations, but the mechanisms underlying such robustness are not well understood. Here, we probe clock robustness to unexpected photic perturbation by measuring the speed of reentrainment of the murine locomotor rhythm after an abrupt advance of the light-dark cycle. Using an intersectional genetic approach, we implicate a critical role for arginine vasopressin pathways, both central within the SCN and peripheral from the anterior pituitary.

Adaptive Locomotion Learning for Quadruped Robots by Combining DRL with a Cosine Oscillator Based Rhythm Controller

Animals have evolved to adapt to complex and uncertain environments, acquiring locomotion skills for diverse surroundings. To endow a robot’s animal-like locomotion ability, in this paper, we propose a learning algorithm for quadruped robots based on deep reinforcement learning (DRL) and a rhythm controller that is based on a cosine oscillator. For a quadruped robot, two cosine oscillators are utilized at the hip joint and the knee joint of one leg, respectively, and, finally, eight oscillators form the controller to realize the quadruped robot’s locomotion rhythm during moving. The coupling between the cosine oscillators of the rhythm controller is realized by the phase difference, which is simpler and easier to realize when dealing with the complex coupling relationship between different joints. DRL is used to help learn the controller parameters and, in the reward function design, we address the challenge of terrain adaptation without relying on the complex camera-based vision processing but based on the proprioceptive information, where a state estimator is introduced to achieve the robot’s posture and help finally utilize the food-end coordinate. Experiments are carried out in CoppeliaSim, and all of the flat, uphill and downhill conditions are considered. The results show that the robot can successfully accomplish all the above skills and, at the same time, with the reward function designed, the robot’s pitch angle, yaw angle and roll angle are very small, which means that the robot is relatively stable during walking. Then, the robot is transplanted to a new scene; the results show that although the environment is previously unencountered, the robot can still fulfill the task, which demonstrates the effectiveness and robustness of this proposed method.

Contributions of M- and Persistent Sodium Currents in Regulating Locomotor Rhythms: A Computational Modeling Study

Physiological experiments have demonstrated that M-current ([Formula: see text]) and persistent sodium current ([Formula: see text]) expressed in rhythm-generating neurons play a key role in the generation and regulation of locomotor rhythms. However, the intrinsic mechanisms by which these two ionic currents control the locomotor rhythms are poorly understood. Here, a computational model is constructed to investigate the roles of [Formula: see text] and [Formula: see text] in regulating locomotor rhythms and explain the underlying ionic mechanisms. The simulation results show that decreasing [Formula: see text] or increasing [Formula: see text] facilitates the generation of the bursting activity; during the bursting activity, the burst frequency of the model has a positive dependence on [Formula: see text], and the flexion-extension as well as left-right coordination are not affected by varying [Formula: see text]. These results accurately reproduce the experimental results. In addition, the results also show that the dependence of burst frequency-[Formula: see text] is similar to that of burst frequency-[Formula: see text], but with distinct regulation mechanisms, i.e. [Formula: see text] regulates the burst frequency by affecting the burst and interburst durations, whereas [Formula: see text] regulates the burst frequency via manipulating the interburst duration. Finally, a dynamical analysis is given to reveal the intrinsic neural mechanisms of [Formula: see text] and [Formula: see text] in regulating the burst properties. Our study provides new insights into how outward and inward currents work in tandem to set the speed of locomotion, and provides testable predictions for biological experimental studies.

Simulated space environmental factors of weightlessness, noise and low atmospheric pressure differentially affect the diurnal rhythm and the gut microbiome

The circadian clock extensively regulates physiology and behavior. In space, astronauts encounter many environmental factors that are dramatically different from those on Earth; however, the effects of these factors on circadian rhythms and the mechanisms remain largely unknown. The present study aimed to investigate the changes in the mouse diurnal rhythm and gut microbiome under simulated space capsule conditions, including microgravity, noise and low atmospheric pressure (LAP). Noise and LAP were loaded in the capsule while the conditions in the animal room remained constant. The mice in the capsule showed disturbed locomotor rhythms and faster adaptation to a 6-h phase advance. RNA sequencing of hypothalamus samples containing the suprachiasmatic nucleus (SCN) revealed that microgravity simulated by hind limb unloading (HU) and exposure to noise and LAP led to decreases in the quantities of differentially expressed genes (DEGs), including circadian clock genes. Changes in the rhythmicity of genes implicated in pathways of cardiovascular deconditioning and more concentrated phases were found under HU or noise and LAP. Furthermore, 16S rRNA sequencing revealed dysbiosis in the gut microbiome, and noise and LAP may repress the temporal discrepancy in the microbiome community structure induced by microgravity. Changes in diurnal oscillations were observed in a number of gut bacteria with critical physiological consequences on metabolism and immunodefense. We also found that the superimposition of noise and LAP may repress normal changes in global gene expression and adaptation in the gut microbiome. Our data demonstrate that in addition to microgravity, exposure to noise and LAP affect the robustness of circadian rhythms and the community structure of the gut microbiome, and these factors may interfere with each other in their adaptation to respective conditions. These findings are important for furthering our understanding of the alterations in circadian rhythms in the complex environment of space.

The deleterious effects and potential therapeutic strategy of fluorene-9-bisphenol on circadian activity and liver diseases in zebrafish and mice

Increasing evidence indicates that disturbance of the clock genes, which leads to systemic endocrine perturbation, plays a crucial role in the pathogenesis of metabolic and liver diseases. Fluorene-9-bisphenol (BHPF) is utilized in the manufacturing of plastic materials but its biological effects on liver homeostasis remain unknown. The impacts and involved mechanisms of BHPF on the liver diseases, metabolism, and circadian clock were comprehensively studied by zebrafish and mouse models. The therapeutic effect of melatonin (MT) was also verified. Zebrafish and mouse models with either acute exposure (0.5 and 1 µmol/L, 1-4 days post-fertilization) or chronic oral exposure (0.5 and 50 mg/(kg·2 days), 30 days) were established with various BHPF concentrations. Herein, we identified a crucial role for estrogenic regulation in liver development and circadian locomotor rhythms damaged by BHPF in a zebrafish model. BHPF mice showed chaos in circadian activity through the imbalance of circadian clock component Brain and Muscle Aryl hydrocarbon receptor nuclear translocator-like 1 in the liver and brain. The liver sexual dimorphic alteration along with reduced growth hormone and estrogens played a critical role in damaged glucose metabolism, hepatic inflammation, and fibrosis induced by BHPF. Besides, sleep improvement by exogenous MT alleviated BHPF‐related glucose metabolism and liver injury in mice. We proposed the pathogenesis of metabolic and liver disease resulting from BHPF and promising targeted therapy for liver metabolism disorders associated with endocrine perturbation chemicals. These results might play a warning role in the administration of endocrine-disrupting chemicals in everyday life and various industry applications.

Continuous Lower Limb Multi‐Intent Prediction for Electromyography‐Driven Intrinsic and Extrinsic Control

Currently, electromyography (EMG)‐driven lower limb control can be divided into computational intrinsic control and interactive extrinsic control based on the participation of neural information in the controllers. However, the former method lacks detailed measurements of the expected motion, whereas the latter is prone to errors in diverse movement situations. Based on this problem, a multi‐intent prediction scheme is proposed that analyzes both rhythmic locomotion and volitional movement intent for AI‐based intrinsic and extrinsic hybrid control (AIEC). A 1D residual shrinkage convolutional network is designed to extract EMG features. The motion state is continuously predicted with an accuracy of 91.66% and the angle completion is also estimated with of 0.9540 and 0.9456 for left and right knee angles, respectively. Additionally, the comparison test further indicates that the motion state classification is significantly improved in the multitask analysis compared with the single‐task approach. This work demonstrates and verifies a novel method in EMG studies that multi‐intent recognition not only compensates for the lack of information in the analysis of single rhythmic or volitional movement, but also enhances the comprehensive performance and makes AIEC feasible, which optimizes the current EMG‐driven control for ampler intent collection and more practical robotic control.

Reversible suppression of circadian-driven locomotor rhythms in mice using a gradual fragmentation of the day-night cycle

Circadian rhythms are regulated by molecular clockwork and drive 24-h behaviors such as locomotor activity, which can be rendered non-functional through genetic knockouts of clock genes. Circadian rhythms are robust in constant darkness (DD) but are modulated to become exactly 24 h by the external day-night cycle. Whether ill-timed light and dark exposure can render circadian behaviors non-functional to the extent of genetic knockouts is less clear. In this study, we discovered an environmental approach that led to a reduction or lack in rhythmic 24-h-circadian wheel-running locomotor behavior in mice (referred to as arrhythmicity). We first observed behavioral circadian arrhythmicity when mice were gradually exposed to a previously published disruptive environment called the fragmented day-night cycle (FDN-G), while maintaining activity alignment with the four dispersed fragments of darkness. Remarkably, upon exposure to constant darkness (DD) or constant light (LL), FDN-G mice lost any resemblance to the FDN-G-only phenotype and instead, exhibited sporadic activity bursts. Circadian rhythms are maintained in control mice with sudden FDN exposure (FDN-S) and fully restored in FDN-G mice either spontaneously in DD or after 12 h:12 h light–dark exposure. This is the first study to generate a light–dark environment that induces reversible suppression of circadian locomotor rhythms in mice.

Persistent Nav1.1 and Nav1.6 currents drive spinal locomotor functions through nonlinear dynamics

Persistent sodium current (INaP) in the spinal locomotor network promotes two distinct nonlinear firing patterns: a self-sustained spiking triggered by a brief excitation in bistable motoneurons and bursting oscillations in interneurons of the central pattern generator (CPG). Here, we identify the NaV channels responsible for INaP and their role in motor behaviors. We report the axonal Nav1.6 as the main molecular player for INaP in lumbar motoneurons. The inhibition of Nav1.6, but not of Nav1.1, in motoneurons impairs INaP, bistability, postural tone, and locomotor performance. In interneurons of the rhythmogenic CPG region, both Nav1.6 and Nav1.1 equally mediate INaP. Inhibition of both channels is required to abolish oscillatory bursting activities and the locomotor rhythm. Overall, Nav1.6 plays a significant role both in posture and locomotion by governing INaP-dependent bistability in motoneurons and working in tandem with Nav1.1 to provide INaP-dependent rhythmogenic properties of the CPG.

Locomotion rhythm makes power and speed

This article addresses two questions, why certain animals (frogs, breaststroke swimmers, hovering fliers, jellyfish) push rapidly against the surrounding fluid and then reach forward slowly, and whether this rhythm of propulsion is a manifestation of the universal phenomenon of design evolution in nature. Emphasis is on the distribution of time periods of locomotion in which, during the driving phase of cyclic movement (the motive stroke, phases 1 and 2, in alternating sequence with the dissipative stroke, phase 3), the work is generated (phase 1) and dissipated (phase 2). The relative lengths of the characteristic times t1 and t2 of the phases 1 and 2, are predicted. The relative duration of the proposed three phases of a cycle is the ‘rhythm’. The analysis is based on a model of how the effective cross-sections of the stroking body parts impact the surrounding medium, water, or air, and the total power required to account for the kinetic energy losses during phases 2 and 3, which are due to drag forces posed by the surrounding medium. The body configuration (limbs' cross-sections) determines the limbs' velocities that maximize mean power, and the times t1 and t2 within the motive stroke. Emphasis is placed on the freedom to change the evolving design. Freedom is represented in two ways: the number of degrees of freedom in changing the dimensions of the model and its deformation in time, and the effect that evolutionary changes have on the access that the body has to its available space. Freedom to change the locomotion design leads to greater power and speed.

Vasculature of the Suprachiasmatic Nucleus: Pathways for Diffusible Output Signals.

Transplant studies demonstrate unequivocally that the suprachiasmatic nucleus (SCN) produces diffusible signals that can sustain circadian locomotor rhythms. There is a vascular portal pathway between the SCN and the organum vasculosum of the lamina terminalis in mouse brain. Portal pathways enable low concentrations of neurosecretions to reach specialized local targets without dilution in the systemic circulation. To explore the SCN vasculature and the capillary vessels whereby SCN neurosecretions might reach portal vessels, we investigated the blood vessels (BVs) of the core and shell SCN. The arterial supply of the SCN differs among animals, and in some animals, there are differences between the 2 sides. The rostral SCN is supplied by branches from either the superior hypophyseal artery (SHpA) or the anterior cerebral artery or the anterior communicating artery. The caudal SCN is consistently supplied by the SHpA. The rostral SCN is drained by the preoptic vein, while the caudal is drained by the basal vein, with variations in laterality of draining vessels. In addition, several key features of the core and shell SCN regions differ: Median BV diameter is significantly smaller in the shell than the core based on confocal image measurements, and a similar trend occurs in iDISCO-cleared tissue. In the cleared tissue, whole BV length density and surface area density are significantly greater in the shell than the core. Finally, capillary length density is also greater in the shell than the core. The results suggest three hypotheses: First, the distinct arterial and venous systems of the rostral and caudal SCN may contribute to the in vivo variations of metabolic and neural activities observed in SCN networks. Second, the dense capillaries of the SCN shell are well positioned to transport blood-borne signals. Finally, variations in SCN vascular supply and drainage may contribute to inter-animal differences.

Influence of coronary artery disease on cardiolocomotor coupling during walking: a preliminary study

The mechanisms involved in the coupling between cardiac and locomotor rhythms in patients with heart disease remain unclear. It was speculated that reduced function of the cardiovascular and/or locomotor systems would increase the coupling of these systems to increase energy efficiency in response to increased energy demand during exercise. We investigated the development of cardiolocomotor coupling (CLC) in patients with coronary artery disease. Eight outpatients with coronary artery disease (CAD group) and eight healthy individuals (control group) underwent cardiopulmonary exercise testing involving a cycle ergometer ramp protocol and treadmill walk test to record CLC strength. The coefficient of determination (R2 value) of the interval between R waves on the electrocardiograph and step interval reflects CLC strength intensity. The Student’s t-test was used to compare cardiopulmonary exercise testing data and R2 values between the study groups. The R2 value was significantly higher in the CAD group than the control group. Peak oxygen uptake and oxygen uptake at the anaerobic threshold were significantly lower in the CAD group than the control group. Our findings showed that CLC intensity was higher in patients with CAD, suggesting that CLC is more likely to occur in individuals with reduced exercise tolerance due to cardiorespiratory deterioration. Key highlights Eight outpatients with coronary artery disease and eight healthy individuals underwent cardiopulmonary exercise and treadmill walk tests to determine cardiolocomotor coupling strength and physiological characteristics. This study reports a stronger cardiolocomotor coupling during exercise in patients with coronary artery disease compared with healthy individuals, suggesting that cardiolocomotor coupling is more likely to occur in people with reduced exercise tolerance attributed to impaired cardiorespiratory function. Our results support the theory that patients with cardiorespiratory impairment due to coronary artery disease have greater dynamic interaction between the locomotor and cardiovascular systems during exercise, which is concurrent with the hypothesis that cardiolocomotor coupling is a compensatory phenomenon for exercise maintenance.

The Compound Eye Regulates Free-Running Period and Stability of the Circadian Locomotor Rhythm in the Cricket Gryllus bimaculatus.

The circadian system of many multicellular organisms consists of a hierarchical structure of multiple clocks, including central and peripheral clocks. The temporal structure has been analyzed in terms of central-to-peripheral regulation but rarely from the opposite perspective. In this study, the potential control of the central clock in the optic lobe by the peripheral clock in the compound eye was investigated in the cricket Gryllus bimaculatus. The locomotor activity rhythm of crickets in which one of the two bilateral optic lobe clocks was surgically removed was tested in constant darkness at three environmental temperatures (20°C, 25°C, and 30°C) and compared with that of crickets in which the optic nerve connecting between the compound eye and optic lobe of the intact side was also severed. When the optic nerve was severed at 30°C, the free-running period and its stability were significantly increased and decreased, respectively, compared to those of intact and sham-operated crickets, whereas at 20°C, only the free-running period was significantly lengthened, and at 25°C, no significant changes were observed in these parameters. At 30°C, the changes in these two parameters were reproduced when the anterior half of the compound eye was removed, while the removal of the posterior half induced period lengthening only. Together with previous data, these results suggest that the free-running period and stability of the locomotor rhythm are regulated through reciprocal coupling between the clocks in the compound eye and the optic lobe.

Sensory conflict disrupts circadian rhythms in the sea anemone Nematostella vectensis.

Circadian clocks infer time of day by integrating information from cyclic environmental factors called zeitgebers, including light and temperature. Single zeitgebers entrain circadian rhythms, but few studies have addressed how multiple, simultaneous zeitgeber cycles interact to affect clock behavior. Misalignment between zeitgebers ('sensory conflict') can disrupt circadian rhythms, or alternatively clocks may privilege information from one zeitgeber over another. Here, we show that temperature cycles modulate circadian locomotor rhythms in Nematostella vectensis, a model system for cnidarian circadian biology. We conduct behavioral experiments across a comprehensive range of light and temperature cycles and find that Nematostella's circadian behavior is disrupted by chronic misalignment between light and temperature, which involves disruption of the endogenous clock itself rather than a simple masking effect. Sensory conflict also disrupts the rhythmic transcriptome, with numerous genes losing rhythmic expression. However, many metabolic genes remained rhythmic and in-phase with temperature, and other genes even gained rhythmicity, implying that some rhythmic metabolic processes persist even when behavior is disrupted. Our results show that a cnidarian clock relies on information from light and temperature, rather than prioritizing one signal over the other. Although we identify limits to the clock's ability to integrate conflicting sensory information, there is also a surprising robustness of behavioral and transcriptional rhythmicity.

Reaction of human walking to transient block of vision: analysis in the context of indirect, referent control of motor actions.

Human locomotion may result from monotonic shifts in the referent position, R, of the body in the environment. R is also the spatial threshold at which muscles can be quiescent but are activated depending on the deflection of the current body configuration Q from R. Shifts in R are presumably accomplished with the participation of proprioceptive and visual feedback and responsible for transferring stable body balance (equilibrium) from one place in the environment to another, resulting in rhythmic activity of multiple muscles by a central pattern generator (CPG). We tested predictions of this two-level control scheme. In particular, in response to a transient block of vision during locomotion, the system can temporarily slow shifts in R. As a result, the phase of rhythmical movements of all four limbs will be changed for some time, even though the rhythm and other characteristics of locomotion will be fully restored after perturbation, a phenomenon called long-lasting phase resetting. Another prediction of the control scheme is that the activity of multiple muscles of each leg can be minimized reciprocally at specific phases of the gait cycle both in the presence and absence of vision. Speed of locomotion is related to the rate of shifts in the referent body position in the environment. Results confirmed that human locomotion is likely guided by feedforward shifts in the referent body location, with subsequent changes in the activity of multiple muscles by the CPG. Neural structures responsible for shifts in the referent body configuration causing locomotion are suggested.

Behavioral circatidal rhythms require Bmal1 in Parhyale hawaiensis

Organisms living in the intertidal zone are exposed to a particularly challenging environment. In addition to daily changes in light intensity and seasonal changes in photoperiod and weather patterns, they experience dramatic oscillations in environmental conditions due to the tides. To anticipate tides, and thus optimize their behavior and physiology, animals occupying intertidal ecological niches have acquired circatidal clocks. Although the existence of these clocks has long been known, their underlying molecular components have proven difficult to identify, in large part because of the lack of an intertidal model organism amenable to genetic manipulation. In particular, the relationship between the circatidal and circadian molecular clocks, and the possibility of shared genetic components, has been a long-standing question. Here, we introduce the genetically tractable crustacean Parhyale hawaiensis as a system for the study of circatidal rhythms. First, we show that P.hawaiensis exhibits robust 12.4-h rhythms of locomotion that can be entrained to an artificial tidal regimen and are temperature compensated. Using CRISPR-Cas9 genome editing, we then demonstrate that the core circadian clock gene Bmal1 is required for circatidal rhythms. Our results thus demonstrate that Bmal1 is a molecular link between circatidal and circadian clocks and establish P.hawaiensis as a powerful system to study the molecular mechanisms underlying circatidal rhythms and their entrainment.

Acquisition of bipedal locomotion in a neuromusculoskeletal model with unilateral transtibial amputation.

Adaptive locomotion is an essential behavior for animals to survive. The central pattern generator in the spinal cord is responsible for the basic rhythm of locomotion through sensory feedback coordination, resulting in energy-efficient locomotor patterns. Individuals with symmetrical body proportions exhibit an energy-efficient symmetrical gait on flat ground. In contrast, individuals with lower limb amputation, who have morphologically asymmetrical body proportions, exhibit asymmetrical gait patterns. However, it remains unclear how the nervous system adjusts the control of the lower limbs. Thus, in this study, we investigated how individuals with unilateral transtibial amputation control their left and right lower limbs during locomotion using a two-dimensional neuromusculoskeletal model. The model included a musculoskeletal model with 7 segments and 18 muscles, as well as a neural model with a central pattern generator and sensory feedback systems. Specifically, we examined whether individuals with unilateral transtibial amputation acquire prosthetic gait through a symmetric or asymmetric feedback control for the left and right lower limbs. After acquiring locomotion, the metabolic costs of transport and the symmetry of the spatiotemporal gait factors were evaluated. Regarding the metabolic costs of transportation, the symmetric control model showed values approximately twice those of the asymmetric control model, whereas both scenarios showed asymmetry of spatiotemporal gait patterns. Our results suggest that individuals with unilateral transtibial amputation can reacquire locomotion by modifying sensory feedback parameters. In particular, the model reacquired reasonable locomotion for activities of daily living by re-searching asymmetric feedback parameters for each lower limb. These results could provide insight into effective gait assessment and rehabilitation methods to reacquire locomotion in individuals with unilateral transtibial amputation.

Adult Neurogenesis Is Altered by Circadian Phase Shifts and the Duper Mutation in Female Syrian Hamsters.

Cell birth and survival in the adult hippocampus are regulated by a circadian clock. Rotating shift work and jet lag disrupt circadian rhythms and aggravate disease. Internal misalignment, a state in which abnormal phase relationships prevail between and within organs, is proposed to account for adverse effects of circadian disruption. This hypothesis has been difficult to test because phase shifts of the entraining cycle inevitably lead to transient desynchrony. Thus, it remains possible that phase shifts, regardless of internal desynchrony, account for adverse effects of circadian disruption and alter neurogenesis and cell fate. To address this question, we examined cell birth and differentiation in the duper Syrian hamster (Mesocricetus auratus), a Cry1-null mutant in which re-entrainment of locomotor rhythms is greatly accelerated. Adult females were subjected to alternating 8 h advances and delays at eight 16 d intervals. BrdU, a cell birth marker, was given midway through the experiment. Repeated phase shifts decreased the number of newborn non-neuronal cells in WT, but not in duper hamsters. The duper mutation increased the number of BrdU-IR cells that stained for NeuN, which marks neuronal differentiation. Immunocytochemical staining for proliferating cell nuclear antigen indicated no overall effect of genotype or repeated shifts on cell division rates after 131 days. Cell differentiation, assessed by doublecortin, was higher in duper hamsters but was not significantly altered by repeated phase shifts. Our results support the internal misalignment hypothesis and indicate that Cry1 regulates cell differentiation. Phase shifts may determine neuronal stem cell survival and time course of differentiation after cell birth. Figure created with BioRender.

Evidence of ancestral nocturnality, locomotor clock regression, and cave zone-adjusted sleep duration modes in a cave beetle

The small carrion beetle Ptomaphagus hirtus is an abundant inhabitant of the exceptionally biodiverse Mammoth Cave system. Previous studies revealed negative phototaxis and the expression of biological clock genes in this microphthalmic cave beetle. Here we present results from probing P. hirtus for the entrainment of locomotor rhythms using the TriKinetics activity monitor setup. Although curtailed by low adjustment frequency of animals to the test environment, the data obtained from successfully monitoring two animals in constant darkness (DD) and six animals exposed to 12 hour light-dark cycles (LD) revealed a strong effect of light on locomotor activity in P. hirtus. In LD, activity was prevalent during the artificial night phases while close to absent during the presumptive day phases, suggesting conserved nocturnality. Upon transitioning LD animals to constant darkness, none displayed detectable evidence of free-running activity rhythms, suggesting complete regression of the central circadian clock. Equally notable, overall locomotor activity of the two DD-monitored animals was about three-fold lower compared to LD animals due to longer rest durations in the former. We, therefore, propose the existence of cave zone-specific energy expenditure modes that are mediated through light schedule responsive modification of sleep duration in P. hirtus.

Deconstructing the modular organization and real-time dynamics of mammalian spinal locomotor networks

Locomotion empowers animals to move. Locomotor-initiating signals from the brain are funneled through descending neurons in the brainstem that act directly on spinal locomotor circuits. Little is known in mammals about which spinal circuits are targeted by the command and how this command is transformed into rhythmicity in the cord. Here we address these questions leveraging a mouse brainstem-spinal cord preparation from either sex that allows locating the locomotor command neurons with simultaneous Ca2+ imaging of spinal neurons. We show that a restricted brainstem area – encompassing the lateral paragigantocellular nucleus (LPGi) and caudal ventrolateral reticular nucleus (CVL) – contains glutamatergic neurons which directly initiate locomotion. Ca2+ imaging captures the direct LPGi/CVL locomotor initiating command in the spinal cord and visualizes spinal glutamatergic modules that execute the descending command and its transformation into rhythmic locomotor activity. Inhibitory spinal networks are recruited in a distinctly different pattern. Our study uncovers the principal logic of how spinal circuits implement the locomotor command using a distinct modular organization.

Dysfunction of Prkcaa Links Social Behavior Defects with Disturbed Circadian Rhythm in Zebrafish.

Protein kinase Cα (PKCα/PRKCA) is a crucial regulator of circadian rhythm and is associated with human mental illnesses such as autism spectrum disorders and schizophrenia. However, the roles of PRKCA in modulating animal social behavior and the underlying mechanisms remain to be explored. Here we report the generation and characterization of prkcaa-deficient zebrafish (Danio rerio). The results of behavioral tests indicate that a deficiency in Prkcaa led to anxiety-like behavior and impaired social preference in zebrafish. RNA-sequencing analyses revealed the significant effects of the prkcaa mutation on the expression of the morning-preferring circadian genes. The representatives are the immediate early genes, including egr2a, egr4, fosaa, fosab and npas4a. The downregulation of these genes at night was attenuated by Prkcaa dysfunction. Consistently, the mutants demonstrated reversed day-night locomotor rhythm, which are more active at night than in the morning. Our data show the roles of PRKCA in regulating animal social interactions and link the social behavior defects with a disturbed circadian rhythm.