Reinforcement feedback impairs locomotor adaptation and retention.

Introduction: Locomotor adaptation is a motor learning process used to alter spatiotemporal elements of walking that are driven by prediction errors, a discrepancy between the expected and actual outcomes of our actions. Sensory and reward prediction errors are two different types of prediction errors that can facilitate locomotor adaptation. Reward and punishment feedback generate reward prediction errors but have demonstrated mixed effects on upper extremity motor learning, with punishment enhancing adaptation, and reward supporting motor memory. However, an in-depth behavioral analysis of these distinct forms of feedback is sparse in locomotor tasks. Methods: For this study, three groups of healthy young adults were divided into distinct feedback groups [Supervised, Reward, Punishment] and performed a novel locomotor adaptation task where each participant adapted their knee flexion to 30 degrees greater than baseline, guided by visual supervised or reinforcement feedback (Adaptation). Participants were then asked to recall the new walking pattern without feedback (Retention) and after a washout period with feedback restored (Savings). Results: We found that all groups learned the adaptation task with external feedback. However, contrary to our initial hypothesis, enhancing sensory feedback with a visual representation of the knee angle (Supervised) accelerated the rate of learning and short-term retention in comparison to monetary reinforcement feedback. Reward and Punishment displayed similar rates of adaptation, short-term retention, and savings, suggesting both types of reinforcement feedback work similarly in locomotor adaptation. Moreover, all feedback enhanced the aftereffect of locomotor task indicating changes to implicit learning. Discussion: These results demonstrate the multi-faceted nature of reinforcement feedback on locomotor adaptation and demonstrate the possible different neural substrates that underly reward and sensory prediction errors during different motor tasks.

Dopamine-sensitive neurons in the mesencephalic locomotor region control locomotion initiation, stop, and turns.

The locomotor role of dopaminergic neurons is traditionally attributed to their ascending projections to the basal ganglia, which project to the mesencephalic locomotor region (MLR). In addition, descending dopaminergic projections to the MLR are present from basal vertebrates to mammals. However, the neurons targeted in the MLR and their behavioral role are unknown in mammals. Here, we identify genetically defined MLR cells that express D1 or D2 receptors and control different motor behaviors in mice. In the cuneiform nucleus, D1-expressing neurons promote locomotion, while D2-expressing neurons stop locomotion. In the pedunculopontine nucleus, D1-expressing neurons promote locomotion, while D2-expressing neurons evoke ipsilateral turns. Using RNAscope, we show that MLR dopamine-sensitive neurons comprise a combination of glutamatergic, GABAergic, and cholinergic neurons, suggesting that different neurotransmitter-based cell types work together to control distinct behavioral modules. Altogether, our study uncovers behaviorally relevant cell types in the mammalian MLR based on the expression of dopaminergic receptors.

Analysis of Differences in Running Demands between Official Matches and Transition Games of Young Professional Soccer Players according to the Playing Position.

The aim of this study was to compare the running demands of transition games (TGs) and official matches, analysing their requirements according to the performance of each position. An observational design was used to examine the activity of 20 soccer players during official matches and TGs. GPS technology was used to monitor the total distance covered (DC), distance at speeds between 14-17.9 km•h-1, 18-21 km•h-1, and above 21 km•h-1, peak speed, accelerations and decelerations above 2.5 m•s-2, and Player Load for both activities. All players were assigned to groups: centre-backs (CBs), fullbacks (FBs), defensive midfielders (DMFs), offensive midfielders (OMFs), wide midfielders (WMFs) and strikers (Ss). TGs showed greater total DC, DC 14-17.9 km•h-1, DC 18-21 km•h-1, DC >21 km•h-1, accelerations and decelerations >2.5 m•s-2, and Player Load (p < 0.01). CBs, FBs and Ss showed more DC, DC 14-17.9 km•h-1, DC 18-21 km•h-1, DC >21 km•h-1, accelerations and decelerations >2.5 m•s-2 and Player Load in TGs (p < 0.01). In the midfielder positions, transition game players showed greater DC 18-21 km•h-1, DC >21 km•h-1, accelerations and decelerations >2.5 m•s-2 than in matches (p < 0.05). DMFs showed higher total DC (p < 0.05) and WMFs greater DC and DC 14-17.9 km•h-1 (p < 0.01) in these drills. During transition games CBs showed greater DC 14-17.9 km•h-1 than FBs, and greater DC than Ss (p < 0.05). FBs performed more decelerations >2.5 m•s-2 than DMFs and OMFs (p < 0.05). TGs produced a homogenized load in soccer players, independent of their position, which exceeded the external load of official matches.

Evaluation of multitarget drugs on the expression of cocaine-induced locomotor sensitization in male rats: A comparative study.

Purpose: - Cocaine use disorder (CUD) is a complex disease. Several studies have shown the efficacy of multitarget drugs used to treat CUD. Here we compare the efficacy of mirtazapine (MIR), pindolol (PIN), fluoxetine (FLX), risperidone (RIS), trazodone (TRZ), ziprasidone (ZPR), ondansetron (OND), yohimbine (YOH), or prazosin (PRZ), to reduce long-term cocaine-induced locomotor activity and the expression of cocaine-induced locomotor sensitization in rats. Methods: - The study consists of four experiments, which were divided into four experimental phases. Induction (10 days), cocaine withdrawal (30 days), expression (10 days), and post-expression phase (10 days). Male Wistar rats were daily dosed with cocaine (10 mg/kg; i.p.) during the induction and post-expression phases. During drug withdrawal, the MIR, PIN, FLX, RIS, TRZ, ZPR, OND, YOH, or PRZ were administered 30 min before saline. In the expression, the multitarget drugs were administered 30 min before cocaine. After each administration, locomotor activity for each animal was recorded for 30 min.During the agonism phase, in experiment four, 8-OH-DPAT, DOI, CP-809-101, SR-57227A, or clonidine (CLO) was administered 30 min before MIR and 60 min before cocaine. After each administration, locomotor activity for each animal was recorded for 30 min. Results: -MIR, FLX, RIS, ZPR, OND, or PRZ attenuated the cocaine-induced locomotor activity and cocaine locomotor sensitization. PIN, TRZ, and YOH failed to decrease cocaine locomotor sensitization. At the optimal doses used, PIN, FLX, RIS, TRZ, ZPR, OND, YOH, or PRZ failed to attenuate long-term cocaine locomotor activation. MIR generated a decrease in cocaine-induced locomotor activity of greater magnitude and duration than the other multitarget drugs evaluated. Conclusion: - At the optimal doses of multitarget drugs evaluated, MIR was the multitarget drug that showed the greatest long-term cocaine-induced behavior effects compared to other multitarget drugs.

Repellent and Attractant Activities of Organic Compounds on Female and Male Philonthus decorus (Coleoptera, Staphylinidae).

The use of organic compounds in different spheres of human activity is accompanied by their influx to and accumulation in the environment. The negative impact of those compounds can be one of the reasons for a decline in populations and biodiversity of aboveground invertebrates. Chemical compounds can potentially cause a variety of effects (attractant or repellent) on insects, including species of the Staphylinidae family. In a laboratory experiment, we identified repellent and attractant influence of 40 organic compounds and mixtures of compounds (acids, alcohols, ketones, phenols, aldehydes, aromatic carbohydrates solvents, and vehicle fuels) on Philonthus decorus Gravenhorst, 1802. The ambulatory responses of the males and females to the same chemical compounds most often varied. A strong repellent activity against both sexes of Ph. decorus was caused by oleic acid, while hexane repelled the males. Acetic acid, 1-butanol, and ammonia solution were found to be strongly repellent against females. A moderate (average) repellent activity towards male Ph. decorus was displayed by organic solvents and fuels, some alcohols (isopropanol, isoamyl alcohol, methanol, ethanol), acids (acetic, formic acid), aromatic carbohydrates (toluene, xylene), and formaldehyde. Female Ph. decorus in general were less sensitive to the odors. The list of repellents with moderate activity against the females was much shorter: solvent 646, white spirit, toluene, isopropanol, isoamyl alcohol, citric and oxalic acids, and glycerol. Moderate attractant activity for Ph. decorus was exhibited by some amino acids, alcohols, and fuel mixes: glycine and L-cysteine (for the males), and phenylalanine, methanol, and diesel fuel (for the females). The rest of the 40 chemical compounds we studied caused no ambulatory responses in Ph. decorus. The difficulties we encountered in the interpretation of the results suggest a need for further experimental studies that would expand the knowledge of the chemoecology of insects.

Analyzing the Effects of Age, Time of Day, and Experiment on the Basal Locomotor Activity and Light-Off Visual Motor Response Assays in Zebrafish Larvae.

The recent availability of commercial platforms for behavioral analyses in zebrafish larvae based on video-tracking technologies has exponentially increased the number of studies analyzing different behaviors in this model organism to assess neurotoxicity. Among the most commonly used assays in zebrafish larvae are basal locomotor activity (BLA) and visual motor responses (VMRs). However, the effect of different intrinsic and extrinsic factors that can significantly alter the outcome of these assays is still not well understood. In this work, we have analyzed the influence of age (5-8 days post-fertilization), time of day (8:00, 10:00, 12:00, 14:00; 16:00, 18:00, and 20:00 h), and experiment (three experiments performed at different days) on BLA and VMR results (4004 analyses for each behavior) in 143 larvae. The results from both behaviors were adjusted to a random-effects linear regression model using generalized least squares (GLSs), including in the model the effect of the three variables, the second-way interactions between them, and the three-way interaction. The results presented in this manuscript show a specific effect of all three intrinsic factors and their interactions on both behaviors, supporting the view that the most stable time period for performing these behavioral assays is from 10:00 am to 04:00 pm, with some differences depending on the age of the larva and the behavioral test.

Two Old Wild-Type Strains of Drosophila melanogaster Can Serve as an Animal Model of Faster and Slower Aging Processes.

BACKGROUND: Drosophila melanogaster provides a powerful platform to study the physiology and genetics of aging, i.e., the mechanisms underpinnings healthy aging, age-associated disorders, and acceleration of the aging process under adverse environmental conditions. Here, we tested the responses of daily rhythms to age-accelerated factors in two wild-type laboratory-adapted strains, Canton-S and Harwich. METHODS: On the example of the 24 h patterns of locomotor activity and sleep, we documented the responses of these two strains to such factors as aging, high temperature, carbohydrate diet, and diet with different doses of caffeine-benzoate sodium. RESULTS: The strains demonstrated differential responses to these factors. Moreover, compared to Canton-S, Harwich showed a reduced locomotor activity, larger amount of sleep, faster rate of development, smaller body weight, lower concentrations of main sugars, lower fecundity, and shorter lifespan. CONCLUSIONS: It might be recommended to use at least two strains, one with a relatively fast and another with a relatively slow aging process, for the experimental elaboration of relationships between genes, environment, behavior, physiology, and health.

The role of fundamental movement skills on children's physical activity during different segments of the school day.

BACKGROUND: Although prior studies have demonstrated that children with high levels of fundamental movement skill (FMS) are more active throughout the day, little is known about children's FMS and their physical activity (PA) during different segments of the school day (e.g., recess, lunch break, and physical education). The present study focused on FMS and moderate-to-vigorous PA (MVPA) during school day and identifies the association between children's FMS and MVPA during different segments of the school day in China. METHODS: A total of 322 children (boys n = 163, girls n = 159; Mage = 8.12, SD = 1.22 years) from four elementary schools involved in this study. Children's FMS and MVPA were measured using the Test of Gross Motor Development-2nd edition (TGMD-2) and hip-mounted accelerometers. Data such as height, weight, and socio-economic status (SES) were also obtained. Multilevel mixed regression models were used to examine the cross-sectional associations between FMS and MVPA. Models were adjusted for gender, age, standardized body mass index, and SES. RESULTS: Children engaged in 32.19 min of MVPA during the whole school day. Boys were more active than girls and had higher object-control skills competency. Locomotor skills were positively associated with children's long recess (B = 1.063) and short recess time (B = 1.502) MVPA. Object-control skills were positively correlated with children's MVPA time during long recess (B = 1.244) and physical education (PE) lessons (B = 1.171). CONCLUSION: The findings highlight the importance of developing both locomotor and object-control skills in elementary schools to lead more MVPA engagement during different segments of the school day.

Preference of position in the proximity of various sugars revealed by location analysis of Drosophila melanogaster.

Feeding behaviors are determined by two main factors. One is the internal state, such as hunger or previous experiences; the other is external factors, such as sensory stimulation. During starvation, animals must balance food-seeking behavior with energy conservation. The fruit fly, Drosophila melanogaster, serves as a useful model for studying food selectivity and various behaviors related to food intake. However, few studies have directly connected food selectivity with other behaviors, such as locomotor activity and sleep. In this study, we report that flies exhibited a preference for specific positions and spent more time in the proximity of sweet sugars, such as sucrose and sucralose, but not non-sweet and nutritious sugars like xylitol and sorbitol. On the other hand, prolonged exposure to sorbitol increased the staying time of flies in the proximity of sorbitol. Additionally, after starvation, flies immediately exhibited a position preference in the proximity of sorbitol. These findings suggest that flies prefer the proximity of sweet food, and starvation alters their preference for nutritious food, which may be beneficial for their survival.

Role of the BCL11A/B homologue Chronophage (Cph) in locomotor behaviour of Drosophila melanogaster.

Functioning of the nervous system requires proper formation and specification of neurons as well as accurate connectivity and signalling between them. Locomotor behaviour depends upon these events that occur during neural development, and any aberration in them could result in motor disorders. Transcription factors are believed to be master regulators that control these processes, but very few linked to behaviour have been identified so far. The Drosophila homologue of BCL11A (CTIP1) and BCL11B (CTIP2), Chronophage (Cph), was recently shown to be involved in temporal patterning of neural stem cells but its role in post-mitotic neurons is not known. We show that knockdown of Cph in neurons during development results in animals with locomotor defects at both larval and adult stages. The defects are more severe in adults, with inability to stand, uncoordinated behaviour and complete loss of ability to walk, climb, or fly. These defects are similar to the motor difficulties observed in some patients with mutations in BCL11A and BCL11B. Electrophysiological recordings showed reduced evoked activity and irregular neuronal firing. All Cph-expressing neurons in the ventral nerve cord are glutamatergic. Our results imply that Cph modulates primary locomotor activity through configuration of glutamatergic neurons. Thus, this study ascribes a hitherto unknown role to Cph in locomotor behaviour of Drosophila melanogaster.

Entomopathogenic fungi-based silver nanoparticles: a potential substitute of synthetic insecticides to counter behavioral and physiological immunity in Aedes aegypti mosquito (Diptera: Culicidae).

Excessive use of synthetic insecticides has resulted in environmental contamination and adverse effects on humans and other non-target organisms. Entomopathogenic fungi offer eco-friendly alternatives; however, their application for pest control requires significant advancement owing to limitations like slow killing time and effectiveness only when applied in higher amounts, whereas exposure to UV radiation, high temperature, and humidity can also reduce their viability and shelf-life. The nanoparticles synthesized using fungal extracellular extracts provide a new approach to use fungal pathogens. Our study focused on the synthesis of Metarhizium anisopliae-based silver nanoparticles (AgNPs) and evaluation of their efficiency on various physiological and behavioral parameters of the mosquito Aedes aegypti. The synthesis, size (27.6 d.nm, PDI = 0.209), zeta potential (- 24.3 mV), and shape of the AgNPs were determined through dynamic light scattering, scanning and transmission electron microscopic, and UV-visual spectroscopic analyses (432 nm). Our results showed significantly reduced survival (100% decrease in case of 3.2 and 1.8 µL/cm2 volumes, and 60% decrease in case of 0.8 µL/cm2 volume), phenoloxidase activity (t = 39.91; p = 0.0001), and gut microbiota, with increased oxidative stress and cell apoptosis in AgNPs-challenged mosquitoes. Furthermore, the AgNPs-exposed mosquitoes presented a concentration-specific decrease in flight locomotor activity (F = 17.312; p < 0.0001), whereas no significant changes in antifungal activity, self-grooming frequencies, or time spent were found. These findings enhance our understanding of mosquito responses to AgNPs exposure, and offer a more efficient mosquito control strategy using entomopathogenic fungi.

Potential Roles of Specific Subclasses of Premotor Interneurons in Spinal Cord Function Recovery after Traumatic Spinal Cord Injury in Adults.

The differential expression of transcription factors during embryonic development has been selected as the main feature to define the specific subclasses of spinal interneurons. However, recent studies based on single-cell RNA sequencing and transcriptomic experiments suggest that this approach might not be appropriate in the adult spinal cord, where interneurons show overlapping expression profiles, especially in the ventral region. This constitutes a major challenge for the identification and direct targeting of specific populations that could be involved in locomotor recovery after a traumatic spinal cord injury in adults. Current experimental therapies, including electrical stimulation, training, pharmacological treatments, or cell implantation, that have resulted in improvements in locomotor behavior rely on the modulation of the activity and connectivity of interneurons located in the surroundings of the lesion core for the formation of detour circuits. However, very few publications clarify the specific identity of these cells. In this work, we review the studies where premotor interneurons were able to create new intraspinal circuits after different kinds of traumatic spinal cord injury, highlighting the difficulties encountered by researchers, to classify these populations.

Vesicular monoamine transporter-2 inhibitor JPC-141 prevents methamphetamine-induced dopamine toxicity and blocks methamphetamine self-administration in rats.

Previous research has demonstrated therapeutic potential for VMAT2 inhibitors in rat models of methamphetamine use disorder. Here, we report on the neurochemical and behavioral effects of 1-(2-methoxyphenethyl)-4-phenethypiperazine (JPC-141), a novel analog of lobelane. JPC-141 potently inhibited (Ki = 52 nM) [3H]dopamine uptake by VMAT2 in striatal vesicles with 50 to 250-fold greater selectivity for VMAT2 over dopamine, norepinephrine and serotonin plasmalemma transporters. Also, JPC-141 was 57-fold more selective for inhibiting VMAT2 over [3H]dofetilide binding to hERG channels expressed by HEK293, suggesting relatively low potential for cardiotoxicity. When administered in vivo to rats, JPC-141 prevented the METH-induced reduction in striatal dopamine content when given either prior to or after a high dose of METH, suggesting a reduction in METH-induced dopaminergic neurotoxicity. In behavioral assays, JPC-141 decreased METH-stimulated locomotor activity in METH-sensitized rats at doses of JPC-141 which did not alter locomotor activity in the saline control group. Moreover, JPC-141 specifically decreased iv METH self-administration at doses that had no effect on food-maintained responding. These findings support the further development of VMAT2 inhibitors as pharmacotherapies for individuals with methamphetamine use disorder.

Dihalogenated nitrophenols exposure induces developmental neurotoxicity in zebrafish embryo.

2,6-Dihalogenated nitrophenols (2,6-DHNPs) are emerging halogenated nitroaromatic pollutants that have been detected in various water environments. However, there is currently limited research available regarding their potential impacts on locomotion behavior and neurotoxicity. Therefore, this study utilized zebrafish embryos to investigate the potential neurotoxic effects of 2,6-DHNPs by examining their impact on the nervous system at a concentration defined as 10% of the median lethal concentration. Our findings demonstrated that exposure to 2,6-DHNPs resulted in a significant 30 % decrease in the total swimming distance of zebrafish larvae, accompanied by notable impairments in motor neuron development and central nervous system. These effects were evidenced by a substantial 25% decrease in axonal growth, as well as disruptions in synapse formation and neuronal differentiation. Additionally, neurotransmitter analysis revealed marked decreases of 40%, 35%, and 30% in dopamine, 5-hydroxytryptamine, and acetylcholine levels respectively, highlighting disturbances in their synthesis, transport, and degradation mechanisms. These results emphasize the considerable neurotoxicity of 2,6-DHNPs at concentrations previously considered safe; thus necessitating a re-evaluation of environmental risk assessments and regulatory standards for such emerging contaminants.

Turns while walking among individuals with Parkinson's disease following overground locomotor training: A pilot study.

BACKGROUND: Individuals with Parkinson's disease are challenged in making turns while walking, evidenced by reduced intersegmental coordination and reduced dynamic postural stability. Although overground locomotor training previously improved ambulation among people with Parkinson's disease, its effect on walking turns remained unknown. We sought to understand the effects of overground locomotor training on walking turns among individuals with mild-Parkinson's disease. METHODS: Twelve participants with Parkinson's (7 Males/5 Females; Age: 68.5 ± 6.4 years) completed twenty-four sessions lasting approximately 60 min and over 12-15 weeks. Baseline and follow-up assessments included the ten-minute walk test using wearable sensors. Primary outcomes included changes to intersegmental coordination, measured by peak rotation and normalized peak rotation, and dynamic postural stability, measured by peak turn velocities in the frontal and transverse planes. Statistical analysis included one-tailed paired t-tests and Cohen's d effect sizes with α = 0.05. FINDINGS: No effects of overground locomotor training on mean peak thoracic rotation (+0.23 ± 4.24°; Cohen's d = 0.05; P = 0.45) or mean normalized peak thoracic rotation (-0.59 ± 5.52 (unitless); Cohen's d = 0.10; P = 0.45) were observed. Moderate and small effects of overground locomotor training were observed on mean peak turn velocities in the frontal (+1.59 ± 2.18°/s; Cohen's d = 0.43; P = 0.01) and transverse planes (+0.88 ± 3.18°/s; Cohen's d = 0.25; P = 0.18). INTERPRETATION: This pilot study provides preliminary evidence suggesting that individuals with mild-Parkinson's moderately improved frontal plane dynamic postural stability after overground locomotor training, likely attenuating the perturbations experienced while turning. CLINICAL TRIAL REGISTRATION: NCT03864393.

Intertwined relationship of dynamin-related protein 1, mitochondrial metabolism and circadian rhythm.

In recent years, mitochondria have gained significant interest in the field of biomedical research due to their impact on human health and ageing. As mitochondrial dynamics are strongly controlled by clock genes, misalignment of the circadian rhythm leads to adverse metabolic health effects. In this review, by exploring various aspects of research and potential links, we hope to update the current understanding of the intricate relationship between DRP1-mediated mitochondrial dynamics and changes in circadian rhythmicity leading to health issues. Thus, this review addresses the potential bidirectional relationships between DRP1-linked mitochondrial function and circadian rhythm misalignment, their impact on different metabolic pathways, and the potential therapeutics for metabolic and systemic disorders.

Motor flexibility to stabilize the toe position during obstacle crossing in older adults: an investigation using an uncontrolled manifold analysis.

Introduction: An age-related decrease in the ability to exploit the abundant degrees of freedom of the body, referred to as motor flexibility, leads to a heightened fall risk. The present study investigated motor flexibility to stabilize the toe position during obstacle crossing in older adults and its correlation with the magnitude of foot elevation. Methods: Twenty-six older adults (70.9 ± 7.4 years old) and 21 younger adults (25.4 ± 5.0 years old) walked and crossed an obstacle, during which the dominant limb was always the leading limb. An uncontrolled manifold (UCM) analysis was used to quantify the flexibility during obstacle crossing as the synergy index, with the vertical toe position being regarded as the performance variable and the segment angles of the lower limbs as the elemental variables. Results and discussion: The results showed that older participants had a significantly lower synergy index for the trailing limb before the moment of obstacle crossing than younger participants, suggesting reduced flexibility in part. The results also showed that, regardless of age, foot elevation was negatively correlated with the synergy index, suggesting that a so-called "conservative strategy" (i.e., a tendency to show extraordinarily high foot elevation to ensure collision avoidance) may be related to their reduced motor flexibility.

Electrical stimulation of the cuneiform nucleus enhances the effects of rehabilitative training on locomotor recovery after incomplete spinal cord injury.

Most human spinal cord injuries are anatomically incomplete, leaving some fibers still connecting the brain with the sublesional spinal cord. Spared descending fibers of the brainstem motor control system can be activated by deep brain stimulation (DBS) of the cuneiform nucleus (CnF), a subnucleus of the mesencephalic locomotor region (MLR). The MLR is an evolutionarily highly conserved structure which initiates and controls locomotion in all vertebrates. Acute electrical stimulation experiments in female adult rats with incomplete spinal cord injury conducted in our lab showed that CnF-DBS was able to re-establish a high degree of locomotion five weeks after injury, even in animals with initially very severe functional deficits and white matter lesions up to 80-95%. Here, we analyzed whether CnF-DBS can be used to support medium-intensity locomotor training and long-term recovery in rats with large but incomplete spinal cord injuries. Rats underwent rehabilitative training sessions three times per week in an enriched environment, either with or without CnF-DBS supported hindlimb stepping. After 4 weeks, animals that trained under CnF-DBS showed a higher level of locomotor performance than rats that trained comparable distances under non-stimulated conditions. The MLR does not project to the spinal cord directly; one of its main output targets is the gigantocellular reticular nucleus in the medulla oblongata. Long-term electrical stimulation of spared reticulospinal fibers after incomplete spinal cord injury via the CnF could enhance reticulospinal anatomical rearrangement and in this way lead to persistent improvement of motor function. By analyzing the spared, BDA-labeled giganto-spinal fibers we found that their gray matter arborization density after discontinuation of CnF-DBS enhanced training was lower in the lumbar L2 and L5 spinal cord in stimulated as compared to unstimulated animals, suggesting improved pruning with stimulation-enhanced training. An on-going clinical study in chronic paraplegic patients investigates the effects of CnF-DBS on locomotor capacity.

Locomotor Assays in Drosophila Larvae and Adult Flies.

Brain defects often lead to motor dysfunctions in humans. Drosophila melanogaster has been one of the most useful organisms in the study of neuronal biology due to its similarities with humans and has contributed to a more detailed understanding of the effects of genetic dysfunctions in the brain on behavior. We herein present modified protocols for the crawling assay with larvae and the climbing assay with adult flies that are simple to perform as well as a series of commands for ImageJ to automatically analyze data for the crawling assay.

Stress responses to bacterial and viral mimetics in polycystic ovary syndrome model rats.

Polycystic ovary syndrome (PCOS) is associated with an increased risk of psychological distress as well as enhanced responses to psychosocial stress. Recently, it was hypothesized that PCOS patients may be at high risk of novel COVID-19 infections and worse clinical presentations during such infections. Here, we evaluated the effects of PCOS on stress responses to bacterial and viral mimetics using dihydrotestosterone-induced PCOS model rats. Lipopolysaccharide (LPS; a bacterial mimetic) or polyinosinic-polycytidylic acid (Poly-IC; a viral mimetic) was injected into PCOS model rats (PCOS) and non-PCOS rats (control), and the rats' stress responses were evaluated. In the PCOS group, the rats' anorectic and febrile responses to LPS injection were enhanced, whereas their anorectic and febrile responses to Poly-IC injection were unaltered. The PCOS group also exhibited greater changes in peripheral cytokine levels in response to LPS, but not Poly-IC. On the contrary, after the injection of Poly-IC depressed locomotor activity was more evident in the PCOS group, whereas no such changes were observed after LPS injection. These findings indicate that although the stress responses of PCOS model rats to infection may be enhanced, the patterns of change in stress responses and their underlying mechanisms may differ between bacterial and viral infections.