Electromechanical enhancement of live jellyfish for ocean exploration.

The vast majority of the ocean's volume remains unexplored, in part because of limitations on the vertical range and measurement duration of existing robotic platforms. In light of the accelerating rate of climate change impacts on the physics and biogeochemistry of the ocean, the need for new tools that can measure more of the ocean on faster timescales is becoming pressing. Robotic platforms inspired or enabled by aquatic organisms have the potential to augment conventional technologies for ocean exploration. Recent work demonstrated the feasibility of directly stimulating the muscle tissue of live jellyfish via implanted microelectronics. We present a biohybrid robotic jellyfish that leverages this external electrical swimming control, while also using a 3D printed passive mechanical attachment to streamline the jellyfish shape, increase swimming performance, and significantly enhance payload capacity. A six-meter-tall, 13 600 l saltwater facility was constructed to enable testing of the vertical swimming capabilities of the biohybrid robotic jellyfish over distances exceeding 35 body diameters. We found that the combination of external swimming control and the addition of the mechanical forebody resulted in an increase in swimming speeds to 4.5 times natural jellyfish locomotion. Moreover, the biohybrid jellyfish were capable of carrying a payload volume up to 105% of the jellyfish body volume. The added payload decreased the intracycle acceleration of the biohybrid robots relative to natural jellyfish, which could also facilitate more precise measurements by onboard sensors that depend on consistent platform motion. While many robotic exploration tools are limited by cost, energy expenditure, and varying oceanic environmental conditions, this platform is inexpensive, highly efficient, and benefits from the widespread natural habitats of jellyfish. The demonstrated performance of these biohybrid robots suggests an opportunity to expand the set of robotic tools for comprehensive monitoring of the changing ocean.

Mechanisms underlying palmitic acid-induced disruption of locomotor activity and sleep behavior in Drosophila.

The globally prevalent of sleep disorders is partly attributed to unhealthy dietary habits. This study investigated the underlying mechanisms of elevated palmitic acid (PA) intake on locomotor activity and sleep behavior in Drosophila. Our results indicate that exposure to PA significantly elevated Drosophila's daytime and nighttime locomotor activity while concurrently reducing overall sleep duration. Utilizing 16S rRNA sequencing, we observed substantial alterations in the composition of the gut microbiota induced by PA, notably, characterized by a significant reduction in Lactobacillus plantarum. Furthermore, PA significantly increased the levels of inflammatory factors Upd3 and Eiger in Drosophila intestines, and downregulated the expression of Gad and Tph, as well as 5-HT1A. Conversely, Gdh and Hdc were significantly upregulated in the PA group. Supplementation with L. plantarum or lactic acid significantly ameliorated PA-induced disruptions in both locomotor activity and sleep behavior. This supplementation also suppressed the expression of intestinal inflammatory factors, thus restoring impaired neurotransmitter-mediated sleep-wake regulation. Moreover, specific knockdown of intestinal epithelial Upd3 or Eiger similarly restored disrupted neurotransmitter expression, ultimately improving PA-induced disturbances in Drosophila locomotor activity and sleep behavior. These findings provide important insights into the intricate interplay between dietary components and essential behaviors, highlighting potential avenues for addressing health challenges associated with modern dietary habits.

Acupuncture has potential in managing axial stiffness in steeplechase racehorses: a blinded prospective randomized preliminary study.

OBJECTIVE: Evaluate the short-term effects of acupuncture on the dynamic manifestations of axial stiffness in steeplechase racehorses. ANIMALS: 12 steeplechase racehorses presenting signs of axial stiffness during training. METHODS: Horses were randomly assigned to either an acupuncture treatment by an experienced certified acupuncturist (n = 6) or no treatment as negative controls (6). The horses' locomotion was evaluated during training before treatment (D0) and 7 (D7) and 14 (D14) days after by their rider and trainer through a questionnaire. Additionally, the improvement of their dorsal flexibility 2 days after treatment was evaluated subjectively at the trot, free jumping at the canter was evaluated by expert clinicians, and free jumping at the trot was evaluated objectively via inertial measurement units. RESULTS: Significantly more horses were improved on D7 and D14 in the acupuncture group (6/6) compared with the control group (1/5; P =.01) according to the scores set by the trainer and riders. Subjective evaluation of the dorsal flexibility also revealed a significant improvement (P = .04) for horses receiving the acupuncture treatment (median improvement score, 0.50 [reference range, 0.5 to 0.9]) compared with control horses (-0.25 [reference range, -0.5 to 0]). CLINICAL RELEVANCE: Acupuncture may be an interesting nondoping strategy to improve clinical signs of axial stiffness and performance on steeplechase racehorses.

Get to the point: Claw morphology impacts frictional interactions on rough substrates.

Claws are a common anatomical feature among limbed amniotes and contribute to a variety of functions including prey capture, locomotion, and attachment. Previous studies of both avian and non-avian reptiles have found correlations between habitat use and claw morphology, suggesting that variation in claw shape permits effective functioning in different microhabitats. How, or if, claw morphology influences attachment performance, particularly in isolation from the rest of the digit, has received little attention. To examine the effects of claw shape on frictional interactions, we isolated the claws of preserved specimens of Cuban knight anoles (Anolis equestris), quantified variation in claw morphology via geometric morphometrics, and measured friction on four different substrates that varied in surface roughness. We found that multiple aspects of claw shape influence frictional interactions, but only on substrates for which asperities are large enough to permit mechanical interlocking with the claw. On such substrates, the diameter of the claw's tip is the most important predictor of friction, with narrower claw tips inducing greater frictional interactions than wider ones. We also found that claw curvature, length, and depth influence friction, but that these relationships depend on the substrate's surface roughness. Our findings suggest that although claw shape plays a critical role in the effective clinging ability of lizards, its relative importance is dependent upon the substrate. Description of mechanical function, as well as ecological function, is critical for a holistic understanding of claw shape variation.

Effects of maternal and offspring treatment with two dietary sources of vitamin D on the mineral homeostasis, bone metabolism and locomotion of offspring fed protein- and phosphorus-reduced diets.

The present study aims to compare the effects of maternal and offspring treatment with 25-hydroxycholecalciferol (25-OHD3) and vitamin D3 on vitamin D status, mineral homoeostasis, bone metabolism and locomotion in the offspring. Either vitamin D3 (50 µg/kg diet) or 25-OHD3 (50 µg/kg diet) was supplemented to the gestation and lactation diets of 49 multiparous sows and/or to the diets of their growing offspring. Treatment of the sows did not affect plasma concentrations of 25-OHD3 of the offspring. Pigs fed 25-OHD3 had higher plasma concentrations of 25-OHD3 than pigs that received vitamin D3 during rearing and fattening. However, neither plasma concentrations of calcium, phosphate and bone markers during the observation period nor bone ash and bone mineral density at slaughter were clearly affected by the treatment. Maternal and offspring treatment with 25-OHD3 instead of vitamin D3 resulted in a slight reduction in the prevalence of leg swelling. In addition, more pigs walked with even steps and normal stride length. Further studies are needed to test whether the slight effects observed in the present experiment are reproducible and of relevance for animal health and welfare. In that case, the underlying mechanisms should be revealed in order to take advantage of potentially beneficial influences especially under certain feeding regimes.

Automatically tracking feeding behavior in populations of foraging C. elegans.

Caenorhabditis elegans feeds on bacteria and other small microorganisms which it ingests using its pharynx, a neuromuscular pump. Currently, measuring feeding behavior requires tracking a single animal, indirectly estimating food intake from population-level metrics, or using restrained animals. To enable large throughput feeding measurements of unrestrained, crawling worms on agarose plates at a single worm resolution, we developed an imaging protocol and a complementary image analysis tool called PharaGlow. We image up to 50 unrestrained crawling worms simultaneously and extract locomotion and feeding behaviors. We demonstrate the tool's robustness and high-throughput capabilities by measuring feeding in different use-case scenarios, such as through development, with genetic and chemical perturbations that result in faster and slower pumping, and in the presence or absence of food. Finally, we demonstrate that our tool is capable of long-term imaging by showing behavioral dynamics of mating animals and worms with different genetic backgrounds. The low-resolution fluorescence microscopes required are readily available in C. elegans laboratories, and in combination with our python-based analysis workflow makes this methodology easily accessible. PharaGlow therefore enables the observation and analysis of the temporal dynamics of feeding and locomotory behaviors with high-throughput and precision in a user-friendly system.

A small worm called C. elegans is constantly hungry. It spends all its time looking for food or eating. Hunger and environmental factors, like light, influence its feeding behavior. Studying these worms has helped scientists learn how feeding affects health, longevity, and aging. Feeding studies might also help scientists learn how the nervous system works and how it controls feeding. Most studies have used one of two approaches. Scientists may measure how much food a group of C. elegans eat by measuring food before and after it is offered to the worms. Or they restrain individual worms and measure the movement of a tube-like muscle, called the pharynx, which the animals use to vacuum up food. Restraining the worms can alter their behavior or brain activity, and studying group feeding habits may miss individual differences, so neither is optimal. Ideally, scientists could measure the feeding activity of many free-ranging worms, but because the movements of the pharynx are small, that too can be a challenge. Bonnard, Liu et al. developed a software tool that automatically detects and measures feeding behavior in a group of about 30 free-ranging C. elegans simultaneously. In the experiments, Bonnard, Liu et al. genetically engineered worms expressing a fluorescent protein in their pharynx, making it possible to measure its movements with a microscope. They used the microscope to capture images of 30-50 animals at a time as they foraged for food in a dish. Then, they used the software to analyze the data they collected. Over three days and five imaging sessions, Bonnard and Liu et al. tracked the feeding behavior of about 1,000 animals under different conditions. The experiments show that the pharynx grows rapidly during early worm development when the worms quadruple their length, but the rate of pharynx muscle contractions stays the same. They also showed the technique could measure feeding behaviors in animals with different genetic backgrounds, ages, or those engaged in behaviors like mating. The tool allows for larger and longer-term studies of worm feeding behaviors than previous approaches. Bonnard, Liu et al. made their software, called PharaGlow, available for use by other researchers. The tool may make feeding measurements a routine part of C. elegans studies. It will allow scientists to gain new insights into the role of feeding in a range of processes, including aging, fitness, mating, and overall health. Follow-up studies could determine if these findings are general strategies that also apply to other animals.

[Central Pattern Generators for Breathing and Gait and Possible Medical Application of Oriental BodyWork: Access to Extrapyramidal and Body Trunk Movement System Through Breathing Methods].

The neurophysiological background of oriental bodywork based on breathing methods is poorly understood. Recently, experimental techniques using genetically engineered animals have been applied to identify and analyze the functions of motor columns such as medial motor column (MMC), known as evolutionarily old locomotion central pattern generators (CPGs) in lamprey. In oriental bodywork between two individuals, locomotion-related body reactions are often observed. In Nishino Breathing Methods (NBM), the extrapyramidal system is likely to be accessed through the practice of Sokushin-kokyu (whole body awareness with breathing), Karin (body axis rotation and reactivation with breathing), and Taiki (body trunk mutual signaling with breathing; the coordination of two individual body trunks). In addition, kinesiological discussions of ancient oriental traditions, such as the practice of mysterious hand-back contact and the active expiration that relates to music and body trunk reaction, are presented. Based on the hypothesis that oriental bodywork is accessing the extrapyramidal body trunk motor system (basal ganglia to spiral locomotion CPGs), this paper discusses the inter-individual body reactions coexisting through different evolutionary levels in multilayered motor systems, and their possible medical applications.

Puffball-Inspired Microrobotic Systems with Robust Payload, Strong Protection, and Targeted Locomotion for On-Demand Drug Delivery.

Microrobots are recognized as transformative solutions for drug delivery systems (DDSs) because they can navigate through the body to specific locations and enable targeted drug release. However, their realization is substantially limited by insufficient payload capacity, unavoidable drug leakage/deactivation, and strict modification/stability criteria for drugs. Natural puffballs possess fascinating features that are highly desirable for DDSs, including a large fruitbody for storing spores, a flexible protective cap, and environmentally triggered release mechanisms. This report presents a puffball-inspired microrobotic system which incorporates an internal chamber for loading large drug quantities and spatial drug separation, and a near-infrared-responsive top-sealing layer offering strong drug protection and on-demand release. These puffball-inspired microrobots (PIMs) display tunable loading capacities up to high concentrations and enhanced drug protection with minimal drug leakage. Upon near-infrared laser irradiation, on-demand drug delivery with rapid release efficiency is achieved. The PIMs also demonstrate translational motion velocities, switchable motion modes, and precise locomotion under a rotating magnetic field. This work provides strong proof-of-concept for a DDS that combines the superior locomotion capability of microrobots with the unique characteristics of puffballs, thereby illustrating a versatile avenue for development of a new generation of microrobots for targeted drug delivery.

Neuroprotective effect of Biochanin a against Bisphenol A-induced prenatal neurotoxicity in zebrafish by modulating oxidative stress and locomotory defects.

Exogenous toxicants cause oxidative stress and damage to brain cells, resulting in inflammation. Neuroinflammation is important in the pathobiology of various neurological illnesses, including Alzheimer's disease (AD). In this context, Bisphenol A (BPA), a common toxin, causes oxidative damage and has been linked to neurological problems. An O-methylated isoflavone known as Biochanin A (5,7-dihydroxy-4'-methoxy-isoflavone, BCA) is considered to be a phytoestrogen, which is abundant in some legume plants and soy which have preventive effects against cancer, osteoporosis, menopausal symptoms and oxidative stress. However, the mechanism by which BCA protected the prenatal neurological stress are not known. So that, in this study we investigated the BCA neuroprotective effect against BPA-induced neuroinflammation in zebrafish embryo models. For this study, fertilized zebrafish embryos are exposed to BPA (1 µM) with or without BCA. Our finding suggested that BCA co-exposure prevented the depletion of antioxidant defense enzymes by BPA and reduced the production of intracellular ROS production, superoxide anion (O2-), lipid peroxidation (LPO), lactate dehydrogenase (LDH) and nitric oxide (NO) levels in the head that aided in safeguarding neuronal development. Baseline locomotion was rendered and a total distance was calculated to assess the motor function. Exposure to BCA increased acetylcholinestrase (AChE) and improved motor neuron functions. It also reduced the pro-inflammatory response expression and prevented neuroinflammation. Our study suggests that BCA has a positive role in the attenuation or amelioration of neuronal oxidative damage and locomotory behaviour induced by BPA.

Dynamic control of visually guided locomotion through corticosubthalamic projections.

Goal-directed locomotion requires control signals that propagate from higher order areas to regulate spinal mechanisms. The corticosubthalamic hyperdirect pathway offers a short route for cortical information to reach locomotor centers in the brainstem. We developed a task in which head-fixed mice run to a visual landmark and then stop and wait to collect the reward and examined the role of secondary motor cortex (M2) projections to the subthalamic nucleus (STN) in controlling locomotion. Our behavioral modeling, calcium imaging, and optogenetics manipulation results suggest that the M2-STN pathway can be recruited during visually guided locomotion to rapidly and precisely control the pedunculopontine nucleus (PPN) of the mesencephalic locomotor region through the basal ganglia. By capturing the physiological dynamics through a feedback control model and analyzing neuronal signals in M2, PPN, and STN, we find that the corticosubthalamic projections potentially control PPN activity by differentiating an M2 error signal to ensure fast input-output dynamics.

Functional Electrical Stimulation (FES) in the Diagnosis and Treatment of Musculoskeletal and Neuromuscular Control Abnormalities in Horses - Selected Case Studies.

When diagnosing neuromuscular injury and pain, the use of biomechanical evaluations to assess the mechanics of movement patterns has been useful in the human population. Functional electrical stimulation (FES) is a technology that can create action potentials to produce musculoskeletal movement that is almost indistinguishable from the voluntary kinematics produced by the nervous system. To create controlled and precise musculoskeletal movements in humans and in horses, FES has been shown to be effective. In humans, the kinematic information obtained from FES data has been utilized to direct further diagnostics, and/or to assist in the development of specific treatment protocols. In addition, since FES creates dynamic movement while in a static position, the ability to isolate the regions of dysfunction improves without the confounding factors of over-the-ground movement and other artifacts caused by environmental stimuli. This paper explores the transfer of the use of FES in human diagnostics to clinical use in horses. Three equine case studies discuss how FES was employed as a tool in the diagnosis and treatment of equine musculoskeletal and neuromuscular control disorders.

Visual recognition of social signals by a tectothalamic neural circuit.

Social affiliation emerges from individual-level behavioural rules that are driven by conspecific signals1-5. Long-distance attraction and short-distance repulsion, for example, are rules that jointly set a preferred interanimal distance in swarms6-8. However, little is known about their perceptual mechanisms and executive neural circuits3. Here we trace the neuronal response to self-like biological motion9,10, a visual trigger for affiliation in developing zebrafish2,11. Unbiased activity mapping and targeted volumetric two-photon calcium imaging revealed 21 activity hotspots distributed throughout the brain as well as clustered biological-motion-tuned neurons in a multimodal, socially activated nucleus of the dorsal thalamus. Individual dorsal thalamus neurons encode local acceleration of visual stimuli mimicking typical fish kinetics but are insensitive to global or continuous motion. Electron microscopic reconstruction of dorsal thalamus neurons revealed synaptic input from the optic tectum and projections into hypothalamic areas with conserved social function12-14. Ablation of the optic tectum or dorsal thalamus selectively disrupted social attraction without affecting short-distance repulsion. This tectothalamic pathway thus serves visual recognition of conspecifics, and dissociates neuronal control of attraction from repulsion during social affiliation, revealing a circuit underpinning collective behaviour.

Targeting thalamic circuits rescues motor and mood deficits in PD mice.

Although bradykinesia, tremor and rigidity are the hallmark motor defects in patients with Parkinson's disease (PD), patients also experience motor learning impairments and non-motor symptoms such as depression1. The neural circuit basis for these different symptoms of PD are not well understood. Although current treatments are effective for locomotion deficits in PD2,3, therapeutic strategies targeting motor learning deficits and non-motor symptoms are lacking4-6. Here we found that distinct parafascicular (PF) thalamic subpopulations project to caudate putamen (CPu), subthalamic nucleus (STN) and nucleus accumbens (NAc). Whereas PF→CPu and PF→STN circuits are critical for locomotion and motor learning, respectively, inhibition of the PF→NAc circuit induced a depression-like state. Whereas chemogenetically manipulating CPu-projecting PF neurons led to a long-term restoration of locomotion, optogenetic long-term potentiation (LTP) at PF→STN synapses restored motor learning behaviour in an acute mouse model of PD. Furthermore, activation of NAc-projecting PF neurons rescued depression-like phenotypes. Further, we identified nicotinic acetylcholine receptors capable of modulating PF circuits to rescue different PD phenotypes. Thus, targeting PF thalamic circuits may be an effective strategy for treating motor and non-motor deficits in PD.

Planktos: An Agent-Based Modeling Framework for Small Organism Movement and Dispersal in a Fluid Environment with Immersed Structures.

Multiscale modeling of marine and aerial plankton has traditionally been difficult to address holistically due to the challenge of resolving individual locomotion dynamics while being carried with larger-scale flows. However, such problems are of paramount importance, e.g., dispersal of marine larval plankton is critical for the health of coral reefs, and aerial plankton (tiny arthropods) can be used as effective agricultural biocontrol agents. Here we introduce the open-source, agent-based modeling software Planktos targeted at 2D and 3D fluid environments in Python. Agents in this modeling framework are relatively tiny organisms in sufficiently low densities that their effect on the surrounding fluid motion can be considered negligible. This library can be used for scientific exploration and quantification of collective and emergent behavior, including interaction with immersed structures. In this paper, we detail the implementation and functionality of the library along with some illustrative examples. Functionality includes arbitrary agent behavior obeying either ordinary differential equations, stochastic differential equations, or coded movement algorithms, all under the influence of time-dependent fluid velocity fields generated by computational fluid dynamics, experiments, or analytical models in domains with static immersed mesh structures with sliding or sticky collisions. In addition, data visualization tools provide images or animations with kernel density estimation and velocity field analysis with respect to deterministic agent behavior via the finite-time Lyapunov exponent.

Impact of Atorvastatin on Skeletal Muscle Mitochondrial Activity, Locomotion and Axonal Excitability-Evidence from ApoE-/- Mice.

The cardiovascular benefit of statins is well established. However, only 20% of high-risk patients remain adequately adherent after 5 years of treatment. Among reasons for discontinuation, statin associated-muscle pain symptoms are the most prevalent. Aim of the present study was to evaluate the impact of high dose atorvastatin on skeletal muscle mitochondrial activity, aerobic and anaerobic exercise, and axonal excitability in a murine model of atherosclerosis. ApoE-/- mice were fed 12 weeks a high-fat high-cholesterol diet alone or containing atorvastatin (40 mg/Kg/day). Outcomes were the evaluation of muscle mitochondrial functionality, locomotion, grip test, and axonal excitability (compound action potential recording analysis of Aα motor propioceptive, Aß mechanoceptive and C nociceptive fibres). Atorvastatin led to a reduction in muscle mitochondrial biogenesis and mitochondrial ATP production. It did not affect muscular strength but led to a time-dependent motor impairment. Atorvastatin altered the responsiveness of mechanoceptive and nociceptive fibres, respectively, the Aß and C fibres. These findings point out to a mild sensitization on mechanical, tactile and pain sensitivity. In conclusion, although the prevalence of muscular side effects from statins may be overestimated, understanding of the underlying mechanisms can help improve the therapeutic approach and reassure adherence in patients needing-to-be-treated.

Subject-Independent Continuous Locomotion Mode Classification for Robotic Hip Exoskeleton Applications.

Autonomous lower-limb exoskeletons must modulate assistance based on locomotion mode (e.g., ramp or stair ascent) to adapt to the corresponding changes in human biological joint dynamics. However, current mode classification strategies for exoskeletons often require user-specific tuning, have a slow update rate, and rely on additional sensors outside of the exoskeleton sensor suite. In this study, we introduce a deep convolutional neural network-based locomotion mode classifier for hip exoskeleton applications using an open-source gait biomechanics dataset with various wearable sensors. Our approach removed the limitations of previous systems as it is 1) subject-independent (i.e., no user-specific data), 2) capable of continuously classifying for smooth and seamless mode transitions, and 3) only utilizes minimal wearable sensors native to a conventional hip exoskeleton. We optimized our model, based on several important factors contributing to overall performance, such as transition label timing, model architecture, and sensor placement, which provides a holistic understanding of mode classifier design. Our optimized DL model showed a 3.13% classification error (steady-state: 0.80 ± 0.38% and transitional: 6.49 ± 1.42%), outperforming other machine learning-based benchmarks commonly practiced in the field (p<0.05). Furthermore, our multi-modal analysis indicated that our model can maintain high performance in different settings such as unseen slopes on stairs or ramps. Thus, our study presents a novel locomotion mode framework, capable of advancing robotic exoskeleton applications toward assisting community ambulation.

Stimulation of Gs signaling in MC4R cells by DREADD increases energy expenditure, suppresses food intake, and increases locomotor activity in mice.

The melanocortin 4 receptor (MC4R) plays an important role in the regulation of appetite and energy expenditure in humans and rodents. Impairment of MC4R signaling causes severe obesity. MC4R mainly couples to the G-protein Gs. Ligand binding to MC4R activates adenylyl cyclase resulting in increased intracellular cAMP levels. cAMP acts as a secondary messenger, regulating various cellular processes. MC4R can also couple with Gq and other signaling pathways. Therefore, the contribution of MC4R/Gs signaling to energy metabolism and appetite remains unclear. To study the effect of Gs signaling activation in MC4R cells on whole body energy metabolism and appetite, we generated a novel mouse strain that expresses a Gs-coupled designer receptors exclusively activated by designer drugs [Gs-DREADD (GsD)] selectively in MC4R-expressing cells (GsD-MC4R mice). Chemogenetic activation of the GsD by a designer drug [deschloroclozapine (DCZ); 0.01∼0.1 mg/kg body wt] in MC4R-expressing cells significantly increased oxygen consumption and locomotor activity. In addition, GsD activation significantly reduced the respiratory exchange ratio, promoting fatty acid oxidation, but did not affect core (rectal) temperature. A low dose of DCZ (0.01 mg/kg body wt) did not suppress food intake, but a high dose of DCZ (0.1 mg/kg body wt) suppressed food intake in MC4R-GsD mice, although either DCZ dose (0.01 or 0.1 mg/kg body wt) did not affect food intake in the control mice. In conclusion, the current study demonstrated that the stimulation of Gs signaling in MC4R-expressing cells increases energy expenditure and locomotor activity and suppresses appetite.NEW & NOTEWORTHY We report that Gs signaling in melanocortin 4 receptor (MC4R)-expressing cells regulates energy expenditure, appetite, and locomotor activity. These findings shed light on the mechanism underlying the regulation of energy metabolism and locomotor activity by MC4R/cAMP signaling.

Neurobehavioral Differences of Valproate and Risperidone on MK-801 Inducing Acute Hyperlocomotion in Mice.

OBJECTIVE: The glutamate system plays a major role in the development of neuropsychiatric disorders such as addiction, epilepsy, dementia, and psychosis. MK-801 (dizocilpine), an uncompetitive N-methyl-D-aspartate (NMDA) receptor antagonist, could increase locomotor activity and stereotyped neurobehaviors mimicking schizophrenic-like features in the mouse model. The study would explore the neuropharmacological differences of risperidone and valproic acid on the MK-801-induced neurobehavioral changes. METHODS: The subjects were male C57BL/6J mice obtained from the National Laboratory Animal Center. Drug effects were assessed using the open field with a video-tracking system and gaiting tests. After habitation, risperidone (0, 0.1 mg/kg) or valproic acid (0, 200 mg/kg) was injected and ran locomotion for 30 mins. Sequentially, mice were followed by intraperitoneal injection (i.p.) with MK-801 (0, 0.2 mg/kg) and ran locomotion for 60 mins. Gaiting behaviors such as step angles, stride lengths, and stance widths were measured following the study drugs. RESULTS: The results showed that risperidone and valproic acid alone could not alter the locomotor activities. Following the MK-801 injection, the travelled distance and speed in the entire open field dramatically increased. The dose 0.1 mg/kg of risperidone could totally inhibit the MK-801-induced hyperlocomotion compared with that of the saline-injected group (p < 0.001). The valproic acid (200 mg/kg) partially suppressed the hyperlocomotion which is induced by MK801. CONCLUSION: The more dominant effect of risperidone to rescue MK-801 induced hyperlocomotion compared with that of valproic acid. The partial suppression of valproic acid may imply the psychopharmacological evidence as adjuvant effect to treat psychotic patients through tuning glutamatergic neurotransmission.

Complementary encoding of spatial information in hippocampal astrocytes.

Calcium dynamics into astrocytes influence the activity of nearby neuronal structures. However, because previous reports show that astrocytic calcium signals largely mirror neighboring neuronal activity, current information coding models neglect astrocytes. Using simultaneous two-photon calcium imaging of astrocytes and neurons in the hippocampus of mice navigating a virtual environment, we demonstrate that astrocytic calcium signals encode (i.e., statistically reflect) spatial information that could not be explained by visual cue information. Calcium events carrying spatial information occurred in topographically organized astrocytic subregions. Importantly, astrocytes encoded spatial information that was complementary and synergistic to that carried by neurons, improving spatial position decoding when astrocytic signals were considered alongside neuronal ones. These results suggest that the complementary place dependence of localized astrocytic calcium signals may regulate clusters of nearby synapses, enabling dynamic, context-dependent variations in population coding within brain circuits.

Co-transmission of neuropeptides and monoamines choreograph the C. elegans escape response.

Co-localization and co-transmission of neurotransmitters and neuropeptides is a core property of neural signaling across species. While co-transmission can increase the flexibility of cellular communication, understanding the functional impact on neural dynamics and behavior remains a major challenge. Here we examine the role of neuropeptide/monoamine co-transmission in the orchestration of the C. elegans escape response. The tyraminergic RIM neurons, which coordinate distinct motor programs of the escape response, also co-express the neuropeptide encoding gene flp-18. We find that in response to a mechanical stimulus, flp-18 mutants have defects in locomotory arousal and head bending that facilitate the omega turn. We show that the induction of the escape response leads to the release of FLP-18 neuropeptides. FLP-18 modulates the escape response through the activation of the G-protein coupled receptor NPR-5. FLP-18 increases intracellular calcium levels in neck and body wall muscles to promote body bending. Our results show that FLP-18 and tyramine act in different tissues in both a complementary and antagonistic manner to control distinct motor programs during different phases of the C. elegans flight response. Our study reveals basic principles by which co-transmission of monoamines and neuropeptides orchestrate in arousal and behavior in response to stress.