Locomotor Behavior Research Articles

Vitamin D Deficiency Does Not Affect Cognition and Neurogenesis in Adult C57Bl/6 Mice.

Vitamin D deficiency is a global problem. Vitamin D, the vitamin D receptor, and its enzymes are found throughout neuronal, ependymal, and glial cells in the brain and are implicated in certain processes and mechanisms in the brain. To investigate the processes affected by vitamin D deficiency in adults, we studied vitamin D deficient, control, and supplemented diets over 6 weeks in male and female C57Bl/6 mice. The effect of the vitamin D diets on proliferation in the neurogenic niches, changes in glial cells, as well as on memory, locomotion, and anxiety-like behavior, was investigated. Six weeks on a deficient diet was adequate time to reach deficiency. However, vitamin D deficiency and supplementation did not affect proliferation, neurogenesis, or astrocyte changes, and this was reflected on behavioral measures. Supplementation only affected microglia in the dentate gyrus of female mice. Indicating that vitamin D deficiency and supplementation do not affect these processes over a 6-week period.

Treatment with quercetin mitigates polystyrene nanoparticle-induced reduction in neuron capacity by inhibiting dopaminergic neurodegeneration and facilitating dopamine metabolism in Caenorhabditis elegans

In organisms, long-term nanopolystyrenes (PS-NPs) exposure can cause toxicity, including neurotoxicity. Quercetin, the flavonol with extensive distribution within plants, possesses diverse biological activities. Nevertheless, the possible effect of quercetin to suppress PS-NPs-induced neurotoxicity and its associated mechanism remains unknown. Thus, in the present work, Caenorhabditis elegans was utilized as the model animal to investigate quercetin's pharmacological effect on suppressing PS-NPs-induced neurotoxicity and the underlying mechanism. PS-NPs exposure at 1–100 μg/L remarkably reduced locomotion behavior, while only PS-NPs exposure at 100 μg/L significantly decrease sensory perception behavior. Meanwhile, the increase in the number of worms with dopaminergic neurodegeneration was detected in nematodes exposed to 100 μg/L PS-NPs and the decreased dopamine content was observed within nematodes exposed to 10–100 μg/L PS-NPs, demonstrating the function of dopaminergic neurodegeneration and disruption of dopamine metabolism in inducing PS-NPs toxicity on neuron capacity. After 100 μg/L PS-NPs exposure, the 25–100 μM quercetin treatment effectively increased the locomotion behavior and the sensory perception behavior. Developmentally, quercetin treatment (100 μM) remarkably enhanced fluorescence intensity while decreasing worm number with neurodegeneration within BZ555 transgenic strains exposed to 100 μg/L PS-NPs. Physiologically, quercetin treatment (100 μM) significantly enhanced dopamine content within nematodes exposed to 100 μg/L PS-NPs. Molecularly, quercetin treatment (100 μM) notably decreased the expressions of genes governing neurodegeneration (mec-4, deg-3, unc-68, itr-1, clp-1, and asp-3) while significantly increasing the expression of genes governing dopamine metabolism (cat-2, cat-1, dop-1, dop-2, dop-3). As revealed by molecular docking results, quercetin might bind to excitotoxic-like ion channels receptors (MEC-4 and DEG-3) and dopamine secreted protein (CAT-2). Consequently, findings in this work demonstrated that long-term PS-NPs exposure within the μg/L range (1–100 μg/L) was toxic to neuron capacity, which was associated with the enhancement in dopaminergic neurodegeneration and disruption of dopamine metabolism. Notably, PS-NPs-mediated neurotoxicity to nematodes is probably suppressed through subsequent quercetin treatment.

Low sucrose diets protect long-term memory and EPA & DHA enriched diets alter insulin resistance in a mouse model of chemotherapy

Chemotherapy-related cognitive impairment (CRCI) and affective symptoms negatively impact quality of life in breast cancer survivors. The aim of this study was to determine the efficacy of high eicosapentaenoic acid + docosahexaenoic acid (EPA+DHA) and low sucrose diets to alleviate these symptoms in a mouse model of chemotherapy. Potential mechanisms involving insulin resistance were explored. We hypothesized that diets enriched in EPA+DHA and low amounts of sucrose would protect against the impact of chemotherapy on measures of CRCI. Female C57Bl/6 mice were randomized to 1 of 4 diets (2% kcal eicosapentaenoic acid + docosahexaenoic acid [EPA+DHA]/high or low sucrose, low omega-3/high or low sucrose) for 6 weeks and treated with two injections of doxorubicin-based chemotherapy or vehicle during week 2 and 4. Behavioral tests were performed 7 days after second injection. Chemotherapy increased serum insulin and decreased body weight, locomotion and exploratory behavior (all p < .05). Low sucrose consumption resulted in better long-term memory regardless of chemotherapy or vehicle injection (p < .05). 2% EPA+DHA consumption lessened insulin resistance (p < .05); however, controlling for body weight attenuated this effect (p = .08). There were no significant differences by diet or injection on liver lipid content; however, liver lipid content was positively correlated with insulin resistance scores (p < .05). Low sucrose diets may protect long-term memory during chemotherapy. The effect of EPA+DHA on insulin resistance and affective side effects during chemotherapy requires further investigation.

Memristive Circuit Implementation of Caenorhabditis Elegans Mechanism for Neuromorphic Computing.

To overcome the energy efficiency bottleneck of the von Neumann architecture and scaling limit of silicon transistors, an emerging but promising solution is neuromorphic computing, a new computing paradigm inspired by how biological neural networks handle the massive amount of information in a parallel and efficient way. Recently, there is a surge of interest in the nematode worm Caenorhabditis elegans (C. elegans), an ideal model organism to probe the mechanisms of biological neural networks. In this article, we propose a neuron model for C. elegans with leaky integrate-and-fire (LIF) dynamics and adjustable integration time. We utilize these neurons to build the C. elegans neural network according to their neural physiology, which comprises: 1) sensory modules; 2) interneuron modules; and 3) motoneuron modules. Leveraging these block designs, we develop a serpentine robot system, which mimics the locomotion behavior of C. elegans upon external stimulus. Moreover, experimental results of C. elegans neurons presented in this article reveals the robustness (1% error w.r.t. 10% random noise) and flexibility of our design in term of parameter setting. The work paves the way for future intelligent systems by mimicking the C. elegans neural system.

Developmental and physiological impacts of pathogenic human huntingtin protein in the nervous system.

Huntington's Disease (HD) is a neurodegenerative disorder, part of the nine identified inherited polyglutamine (polyQ) diseases. Most commonly, HD pathophysiology manifests in middle-aged adults with symptoms including progressive loss of motor control, cognitive decline, and psychiatric disturbances. Associated with the pathophysiology of HD is the formation of insoluble fragments of the huntingtin protein (htt) that tend to aggregate in the nucleus and cytoplasm of neurons. To track both the intracellular progression of the aggregation phenotype as well as the physiological deficits associated with mutant htt, two constructs of human HTT were expressed with varying polyQ lengths, non-pathogenic-htt (Q15, NP-htt) and pathogenic-htt (Q138, P-htt), with an N-terminal RFP tag for in vivo visualization. P-htt aggregates accumulate in the ventral nerve cord cell bodies as early as 24 hours post hatching and significant aggregates form in the segmental nerve branches at 48 hours post hatching. Organelle trafficking up-and downstream of aggregates formed in motor neurons showed severe deficits in trafficking dynamics. To explore putative downstream deficits of htt aggregation, ultrastructural changes of presynaptic motor neurons and muscles were assessed, but no significant effects were observed. However, the force and kinetics of muscle contractions were severely affected in P-htt animals, reminiscent of human chorea. Reduced muscle force production translated to altered locomotory behavior. A novel HD aggregation model was established to track htt aggregation throughout adulthood in the wing, showing similar aggregation patterns with larvae. Expressing P-htt in the adult nervous system resulted in significantly reduced lifespan, which could be partially rescued by feeding flies the mTOR inhibitor rapamycin. These findings advance our understanding of htt aggregate progression as well the downstream physiological impacts on the nervous system and peripheral tissues.

Conjunctive processing of spatial border and locomotion in retrosplenial cortex during spatial navigation.

Spatial information and dynamic locomotor behaviours are equally important for achieving locomotor goals during spatial navigation. However, it remains unclear how spatial and locomotor information is integrated during the processing of self-initiated spatial navigation. Anatomically, the retrosplenial cortex (RSC) has reciprocal connections with brain regions related to spatial processing, including the hippocampus and para-hippocampus, and also receives inputs from the secondary motor cortex. In addition, RSC is functionally associated with allocentric and egocentric spatial targets and head-turning. So, RSC may be a critical region for integrating spatial and locomotor information. In this study, we first examined the role of RSC in spatial navigation using the Morris water maze and found that mice with inactivated RSC took a longer time and distance to reach their destination. Then, by imaging neuronal activity in freely behaving mice within two open fields of different sizes, we identified a large proportion of border cells, head-turning cells and locomotor speed cells in the superficial layer of RSC. Interestingly, some RSC neurons exhibited conjunctive coding for both spatial and locomotor signals. Furthermore, these conjunctive neurons showed higher prediction accuracy compared with simple spatial or locomotor neurons in special navigator scenes using the border, turning and positive-speed conjunctive cells. Our study reveals that the RSC is an important conjunctive brain region that processes spatial and locomotor information during spatial navigation. KEY POINTS: Retrosplenial cortex (RSC) is indispensable during spatial navigation, which was displayed by the longer time and distance of mice to reach their destination after the inactivation of RSC in a water maze. The superficial layer of RSC has a larger population of spatial-related border cells, and locomotion-related head orientation and speed cells; however, it has few place cells in two-dimensional spatial arenas. Some RSC neurons exhibited conjunctive coding for both spatial and locomotor signals, and the conjunctive neurons showed higher prediction accuracy compared with simple spatial or locomotor neurons in special navigation scenes. Our study reveals that the RSC is an important conjunctive brain region that processes both spatial and locomotor information during spatial navigation.

Neurotoxicity induced by aged microplastics from plastic bowls: Abnormal neurotransmission in Caenorhabditis elegans

The use of plastic bowls (PB) has garnered increasing scrutiny due to the inevitable generation of microplastics (MPs) throughout their lifecycle. Despite this concern, there exists a limited understanding of the behaviors, toxicological effects, and mechanisms associated with aged PB (A-PB). This research investigated the photoaging properties of A-PB following ultraviolet irradiation and evaluated the neurotoxic impact of exposure to A-PB at environmentally relevant concentrations (0.001–1 mg/L) on Caenorhabditis elegans. Significant alterations in the crystallinity, elemental composition, and functional groups of A-PB were observed compared to virgin PB (V-PB), along with the emergence of environmentally persistent free radicals and reactive oxygen species. Toxicity assessments revealed that exposure to 0.1–1 mg/L A-PB induced greater neurotoxicity on locomotion behaviors compared to V-PB, as evidenced by marked reductions in head thrashes, body bends, wavelength, and mean amplitude. Exposure to A-PB also altered the fluorescence intensities and neurodegeneration percentage of dopaminergic, serotonergic, and GABAergic neurons, suggesting neuronal damage in the nematodes. Correspondingly, decreases in the levels of dopamine, serotonin, and GABA were noted together with significant drops in the expression of neurotransmitter-related genes (e.g., dat-1, tph-1, and unc-47). Correlation analyses established a significant positive relationship between these genes and locomotion behaviors. Further exploration showed the absence of locomotion behaviors in dat-1 (ok157), tph-1 (mg280), and unc-47 (e307) mutants, underscoring the pivotal roles of the dat-1, tph-1, and unc-47 genes in mediating neurotoxicity in C. elegans. This study sheds light on the photoaging characteristics and heightened toxicity of A-PB, elucidating the mechanisms driving A-PB-induced neurotoxicity.

Opioid-environment interaction: Contrasting effects of morphine administered in a novel versus familiar environment on acute and repeated morphine induced behavioral effects and on acute morphine ERK activation in reward associated brain areas

We report that environmental context can have a major impact on morphine locomotor behavior and ERK effects. We manipulated environmental context in terms of an environmental novelty/ familiarity dimension and measured morphine behavioral effects in both acute and chronic morphine treatment protocols. Wistar rats (n=7 per group) were injected with morphine 10 mg/kg or vehicle (s.c.), and immediately placed into an arena for 5 min, and locomotor activity was measured after one or 5 days. The morphine treatments were initiated either when the environment was novel or began after the rats had been familiarized with the arena by being given 5 daily nondrug tests in the arena. The results showed that acute and chronic morphine effects were strongly modified by whether the environment was novel or familiar. Acute morphine administered in a novel environment increased ERK activity more substantially in several brain areas, particularly in reward-associated areas such as the VTA in comparison to when morphine was given in a familiar environment. Repeated morphine treatments initiated in a novel environment induced a strong locomotor sensitization, whereas repeated morphine treatments initiated in a familiar environment did not induce a locomotor stimulant effect but rather a drug discriminative stimulus dis-habituation effect. The marked differential effects of environmental novelty/familiarity and ongoing dopamine activity on acute and chronic morphine treatments may be of potential clinical relevance for opioid drug addiction.

What do glass sponges do when no one is looking? Vazella pourtalesii: Responses to sediment deposition, passive locomotion, and contracting behavior

Behavioral response of deep-sea sponges can provide crucial insights into the mechanisms shaping energy fluxes and ecosystem functioning. Although some advances have been made, the behavior of deep-sea Hexactinellid still remain widely unknown. In the present study we address the glass sponge Vazella pourtalesii behavior. High-temporal resolution imaging and environmental data were acquired with an autonomous lander deployed in the Sambro Bank Sponge Conservation Area (Scotian Shelf) at a depth of 150 m, representing the upper limit of this deep-sea species' distribution and what is commonly regarded as the deep sea.For 94 days, a V. pourtalesii individual was monitored, providing quantitative information on its response to sediment deposition triggered by a storm, as well as on its passive locomotion and contractive behavior. Sediment was cleared from its surface within 72 h, which is highly relevant for its filtering capacity, indicating that this sponge species can cope with high suspended sediment concentrations. This enables it to occur on sedimentary environments like the Scotian Shelf. As observed in other deep-sea hexactinellids, the monitored individual engaged in rhythmic contractions, which appear to be driven by physiological process/es rather than environmental factors. During the study period, strong bottom currents (>37 cm/s) toppled and displaced the monitored individual several times. Despite changes in position and orientation that can negatively impact the filtering capacity of sponges, no signs of deterioration were observed. V. pourtalesii's vase-like body morphology and attachment to cobbles, as a gravitational center, may allow it to have a more homogeneous interaction with currents which may permit them to better cope with positional changes. Overall, this study highlights that deep-sea Porifera display a wide array of phenological changes in response to both biotic and abiotic factors.

Rattling the cage: Behaviour and resource use of mice in laboratory and pet cages

Conventional housing for laboratory mice limits the expression of species-specific behaviours and restricts the control over their environment, thus failing to guarantee the animals’ welfare. To better understand the behaviour and resource use of laboratory mice, we housed mice (n = 64) of two common laboratory strains (C57BL/6 and Swiss), both sexes and two group sizes (3 and 5) in large extensively enriched pet cages and conventional laboratory cages, respectively, and assessed their behaviour, resource use, and space use under these different housing conditions. Mice in pet cages showed more running, mostly on the running disc, and other locomotor behaviour, but also spent much time hidden in deep bedding, while mice in conventional laboratory cages climbed more on the cage grid, reared more and exhibited more stereotypic behaviour. Our findings emphasize the significance of a proper substrate for shelter, as well as other resources that facilitate species-specific behaviour.

Subchronic Effects of Tetrachloroethylene on Two Freshwater Copepod Species: Implications for Groundwater Risk Assessment.

Aliphatic chlorinated hydrocarbons, notably tetrachloroethylene (also known as perchloroethylene [PCE]), are persistent, mobile, and toxic (PMT) and/or very persistent, mobile, and toxic (vPMT) groundwater pollutants, often exceeding safe drinking water thresholds. The present study delves into the groundwater risk assessment of PCE with a novel focus on the sensitivity of stygobitic species-organisms uniquely adapted to groundwater environments. Through a comparative analysis of the subchronic effects of PCE on the locomotion behavior of two copepod species, the stygobitic Moraria sp. and the nonstygobitic Bryocamptus zschokkei, we highlighted the inadequacy of the current European predicted-no-effect concentration of PCE for groundwater ecosystems. Our findings indicate significant behavioral impairments in both species at a concentration (32 ng/L PCE) well below the threshold deemed safe, suggesting that the current European guidelines for groundwater risk assessment may not adequately protect the unique biodiversity of groundwater habitats. Importantly, B. zschokkei demonstrated sensitivity to PCE comparable to or greater than that of the target stygobitic species, suggesting its utility as a substitute species in groundwater risk assessment. The present study adds to the limited research on the ecotoxicological sensitivity of groundwater species to PMT/vPMT chemicals and highlights the need for refined groundwater risk-assessment methodologies that consider the susceptibilities of stygobitic species. Environ Toxicol Chem 2024;00:1-13. © 2024 The Author(s). Environmental Toxicology and Chemistry published by Wiley Periodicals LLC on behalf of SETAC.

Preparation of PBAT microplastics and their potential toxicity to zebrafish embryos and juveniles

The extensive use of traditional non-biodegradable plastics results in the generation of microplastics (MPs), forming a new pollutant that can pose significant environmental risks. Biodegradable plastics (BP) possess degradation properties and can partially replace conventional plastics, thereby reducing pollution. However, further investigation is needed into the toxicity of biodegradable microplastics (BMPs) on aquatic organisms. This study explores the toxic effects of PBAT microplastics (PBAT-BMPs) and microplastics produced from degradable PBAT/TPS (thermoplastic starch) composite film (PBAT/TPS-BMPs) on zebrafish embryos. Our findings indicate that the presence of microplastics on the embryo's surface increases with higher BMPs concentration. Nonetheless, PBAT-BMPs tend to aggregate and are blocked by the embryonic membrane, thus diminishing their toxic effects on the embryo. Acute toxicity experiments revealed that 30 mg/L of PBAT-BMPs significantly reduced the survival rate of zebrafish embryos, whereas PBAT/TPS-BMPs had a lesser effect on survival. Both types of BMPs influenced the hatching rate of the embryos, leading to prolonged incubation periods. Additionally, both types of BMPs impacted the locomotor behavior of zebrafish larvae, causing an increase in larval locomotor speed. However, these BMPs had little impact on larval body development and heartbeat behavior. Fluorescent microplastic tracer experiments demonstrated that PBAT-BMPs persisted in juvenile fish for at least 144 h and were difficult to metabolize and excrete. Our study aims to gain a better understanding of the potential effects of BMPs on aquatic ecosystems and biological health, as well as to propose effective strategies for reducing environmental pollution and protecting organisms.

Anxiety and risk-taking behavior maps onto opioid and alcohol polysubstance consumption patterns in male and female mice.

Polysubstance use is prevalent in the population but remains understudied in preclinical models. Alcohol and opioid polysubstance use is associated with negative outcomes, worse treatment prognosis, and higher overdose risk; but underlying mechanisms are still being uncovered. Examining factors that motivate use of one substance over another in different contexts in preclinical models will better our understanding of polysubstance use and improve translational value. Here we assessed baseline anxiety-like and locomotive behavior and then measured voluntary consumption of multiple doses of alcohol and fentanyl in group housed male and female mice using our novel Socially Integrated Polysubstance (SIP) system. Fifty-six male (n=32) and female (n=24) adult mice were housed in groups of 4 for one week with continuous access to food, water, two doses of ethanol (5% and 10%) and two doses of fentanyl (5 ug/ml and 20 ug/ml). Our analyses revealed sex differences across multiple domains - female mice consumed more liquid in the dark cycle, had higher activity, a higher preference for both ethanol and fentanyl over water, and their fentanyl preference increased over the seven days. We then used machine-learning techniques to reveal underlying relationships between baseline behavioral phenotypes and subsequent polysubstance consumption patterns, where anxiety-and risk-taking-like behavioral phenotypes mapped onto discrete patterns of polysubstance use, preference, and escalation. By simulating more translationally relevant substance use and improving our understanding of the motivations for different patterns of consumption, this study contributes to the developing preclinical literature on polysubstance use with the goal of facilitating better treatment outcomes and novel therapeutic strategies.

Enhancing hoof health and locomotion in crossbred dairy cows: impact of recycled manure solids bedding on lameness incidence and gait kinematics.

Recycled manure solids has emerged as a promising alternative for animal bedding, owing to its economic feasibility, ready availability on farms, and soft, non-abrasive nature. This research aimed to assess the impact of recycled manure solids (RMS) bedding, combined with a conditioner containing 7.5% lime and 6% sodium hydrosulphate, on dairy cow welfare and gait kinematics over three months. Hock and knee injury scores, lameness incidence, and gait kinematic parameters were evaluated for animals housed on cement flooring (Control), RMS bedding (Treatment I), and conditioner-added RMS bedding (Treatment II) on days 0, 45, and 90 of the experiment with six crossbred cows in each group. The results revealed a significant reduction (p < 0.05) in lameness scores (5-point scale) for animals in both the RMS and conditioner-added RMS groups, with scores of 1.09 ± 0.05 and 1.04 ± 0.03, respectively, compared to those on cement floors. Moreover, a noteworthy decrease (p < 0.05) in knee and hock injury scores (4-point scale) was observed in the RMS groups, indicating a potentially positive impact on joint health. Gait kinematic analysis demonstrated that animals in the RMS (1.03 ± 0.04m/s) and conditioner-added RMS (1.02 ± 0.06m/s) groups exhibited higher walking speeds and increased step angles (158.59 ± 4.82° and 149.58 ± 3.85°) compared to their cement-floor counterparts. No significant changes (p > 0.05) were observed in stride length, step asymmetry, step length, and step width. The study concluded that the conditioner incorporated recycled manure solids resulting in a substantial decrease in lameness incidence and a reduction in hock and knee injuries among dairy cows. Additionally, the improved gait kinematics observed in non-lame animals suggest that this bedding combination positively influences overall animal well-being. These findings underscore the potential of sustainable bedding practices to enhance both physical health and locomotor behaviour in dairy cattle.

Toxicity of soil leaching liquor from coking plant in developmental zebrafish embryos/larvae model.

The coking industry in China is the largest coke supplier in the world. Contaminated soil in industrial areas poses a serious threat to human and ecosystems. Most of the studies investigated the toxicity of soil from coking plant on soil microorganisms, while the toxic effects of soil leaching liquor on aquatics are limited. In this study, the composition of soil leaching liquor from a coking plant in Taiyuan (TY) was analyzed, and the developmental toxicity on zebrafish was evaluated. The results showed that a total of 91 polycyclic aromatic hydrocarbons were detected in the leaching liquor, followed by phenols and benzene series. The leaching liquor induced developmental impairment in zebrafish larvae, including delayed incubation, deficits in locomotor behavior, vascular and cardiac dysplasia, and impaired neurodevelopment. The results of metabolomics analysis showed that TY soil leaching liquor induced significant metabolic profile disturbances in zebrafish embryos/larvae. The developmental toxicity of the leaching liquor metabolic disorders may be associated with the leaching liquor-induced abnormalities in zebrafish embryonic development. Metabolic pathways were identified by arginine and proline metabolism, phosphotransferase system, starch and sucrose metabolism, steroid biosynthesis, beta-alanine metabolism, and nucleotide metabolism pathways.

Benzofuran Iboga-Analogs Modulate Nociception and Inflammation in an Acute Mouse Pain Model.

Pain management following acute injury or post-operative procedures is highly necessary for proper recovery and quality of life. Opioids and non-steroidal anti-inflammatory drugs (NSAIDS) have been used for this purpose, but opioids cause addiction and withdrawal symptoms whereas NSAIDS have several systemic toxicities. Derivatives of the naturally occurring iboga alkaloids have previously shown promising behavior in anti-addiction of morphine by virtue of their interaction with opioid receptors. On this frontier, four benzofuran analogs of the iboga family have been synthesized and their analgesic effects have been studied in formalin induced acute pain model in male Swiss albino mice at 30 mg/kg of body weight dose administered intraperitoneally. The antioxidant, anti-inflammatory and neuro-modulatory effects of the analogs were analyzed. Reversal of tail flick latency, restricted locomotion and anxiogenic behavior were observed in iboga alcohol, primary amide and secondary amide. Local neuroinflammatory mediators' substance P, calcitonin gene related peptide, cyclooxygenase-2 and p65 were significantly decreased whereas the depletion of brain derived neurotrophic factor and glia derived neurotrophic factor was overturned on iboga analog treatment. Behavioral patterns after oral administration of the best analog were also analyzed. Taken together, these results show that the iboga family of alkaloid has huge potential in pain management.

Muscular expression of pezo-1 differentially contributes to swimming and crawling production in the nematode C. elegans.

Mechanosensitive PIEZO ion channels are evolutionarily conserved proteins that are widely expressed in neuronal and muscular tissues. This study explores the role of the mechanoreceptor PEZO-1 in the body wall muscles of Caenorhabditis elegans, focusing on its influence on two locomotor behaviors, swimming and crawling. Using confocal imaging, we reveal that PEZO-1 localizes to the sarcolemma and plays a crucial role in modulating calcium dynamics that are important for muscle contraction. When we knocked down pezo-1 expression in striated muscles with RNA interference, calcium levels in head and tail muscles increased. While heightened, the overall trajectory of the calcium signal during the crawl cycle remained the same. While downregulation of pezo-1 led to an increase in crawling speed, it caused a reduction in swimming speed. Reduction in pezo-1 expression also resulted in the increased activation of the ventral tail muscles, and a disruption of dorsoventral movement asymmetry, a critical feature that enables propulsion in water. These alterations were correlated with impaired swimming posture and path curvature, suggesting that PEZO-1 has different functions during swimming and crawling.

Peripubertal antagonism of corticotropin-releasing factor receptor 1 results in sustained, sex-specific changes in behavioral plasticity and the transcriptomic profile of the amygdala.

Peripuberty is a significant period of neurodevelopment with long-lasting effects on the brain and behavior. Blocking type 1 corticotropin-releasing factor receptors (CRFR1) in neonatal and peripubertal rats attenuates detrimental effects of early-life stress on neural plasticity, behavior, and stress hormone action, long after exposure to the drug has ended. CRFR1 antagonism can also impact neural and behavioral development in the absence of stressful stimuli, suggesting sustained alterations under baseline conditions. To investigate this further, we administered a CRFR1 antagonist (CRFR1a), R121919, to young adolescent male and female rats across 4 days. Following each treatment, rats were tested for locomotion, social behavior, mechanical allodynia, or PPI of the acoustic startle reflex. Acute CRFR1 blockade immediately reduced PPI in peripubertal males, but not females. In adulthood, each assay was repeated without CRFR1a exposure to test for long-term effects of the adolescent treatment, with males continuing to experience deficits in PPI, while females displayed altered locomotion, PPI, and social behavior. The amygdala was collected to measure long-term effects on gene expression in pathways related to neural plasticity and neurodevelopmental disorders. Relative expression of cannabinoid type 1 receptors (CB1R), which mediate sensorimotor and HPA function, was also measured. In the adult amygdala, peripubertal CRFR1a induced alterations in pathways related to neural plasticity and stress in males and lower expression of CB1R protein in females. Understanding how acute exposure to neuropharmacological agents can have sustained impacts on brain and behavior, in the absence of further exposures, has important clinical implications for adolescent psychiatric treatment protocols.

Isolation and characterization of NGFFYamide neuropeptide from Patiria pectinifera pyloric caeca extract

Neuropeptides are small molecules that mediate intercellular signaling and regulate physiological processes. Starfish possess various myoactive neuropeptides, including starfish myorelaxant peptide (SMP) and a calcitonin-type peptide with apical muscle relaxing properties. In this study, we report the purification of a neuropeptide from starfish (Patiria pectinifera) pyloric caeca extract using high-performance liquid chromatography (HPLC) and an in vitro bioassay to screen for fractions and peptides with relaxing effects on P. pectinifera apical muscle preparations. A series of HPLC steps using reversed-phase and cation-exchange columns yielded a purified peptide with muscle-relaxing effects. The purified peptide's structure was determined by LC-MS and Edman degradation, revealing a pentapeptide with an amidated C-terminus (NGFFYamide) and a molecular mass of 646.2930 Da. This is the first report of NGFFYamide purification from P. pectinifera through biochemical methods. The nucleotide sequence encoding the NGFFYamide precursor was determined, showing the presence of a conserved neurophysin domain in the C-terminal region. RT-qPCR results confirmed high expression in radial nerves cord, consistent with previous findings on NG peptides in echinoderms. In vitro pharmacological studies on muscle preparations from P. pectinifera and Asterias amurensis revealed differential relaxing activity of NGFFYamide on apical muscles, while its effects on tube foot preparations were similar in both species. NGFFYamide also induced potent contraction in P. pectinifera cardiac stomach. Comparison of three NG peptides (NGFFYamide, NGFFFamide, and NGIWYamide) on P. pectinifera cardiac stomach revealed varying potency, suggesting class-specific receptor interactions. Tachyphylaxis was observed in P. pectinifera apical muscle but not in A. amurensis, warranting further investigation. Based on these results, it is plausible that NGFFYamide could be involved in regulating locomotion and feeding behavior in P. pectinifera, consistent with findings in Asterias rubens.

Lactating striped hamsters (Cricetulus barabensis) do not decrease the thermogenic capacity to cope with extreme cold temperature

For small non-hibernating mammals, a high thermogenic capacity is important to increase activity levels in the cold. It has been previously reported that lactating females decrease their thermogenic activity of brown adipose tissue (BAT), whereas their capacity to cope with extreme cold remains uncertain. In this study we examined food intake, body temperature and locomotor behavior, resting metabolic rate, non-shivering thermogenesis, and cytochrome c oxidase activity, and the rate of state 4 respiration of liver, skeletal muscle, and BAT in striped hamsters (Cricetulus barabensis) at peak lactation and non- breeding hamsters (controls). The lactating hamsters and non- breeding controls were acutely exposed to −15°C, and several markers indicative of thermogenic capacity were examined. In comparison to non-breeding females, lactating hamsters significantly increased food intake and body temperature, but decreased locomotor behavior, and the BAT mass, indicative of decreased BAT thermogenesis at peak lactation. Unexpectedly, lactating hamsters showed similar body temperature, resting metabolic rate, non-shivering thermogenesis with non-breeding females after acute exposure to −15°C. Furthermore, cytochrome c oxidase activity of liver, skeletal muscle and BAT, and serum thyroid hormone concentration, and BAT uncoupling protein 1 expression, in lactating hamsters were similar with that in non-breeding hamsters after acute extreme cold exposure. This suggests that lactating females have the same thermogenic capacity to survive cold temperatures compared to non-breeding animals. This is particularly important for females in the field to cope with cold environments during the period of reproduction. Our findings indicate that the females during lactation, one of the highest energy requirement periods, do not impair their thermogenic capacity in response to acute cold exposure.