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Matsumura, K.

Publications and source records attributed to Matsumura, K..

17 recordsLinked to original sources

AMADEUS: Annotation-free multi-animal direction estimation using self-supervised learning

Markerless multi-animal tracking has advanced rapidly, yet measuring social interactions among visually similar animals remains challenging during occlusion and crowding. Here we present AMADEUS (Annotation-free Multi-Animal Direction Estimation Using Self-supervised learning), a tracking system that requires neither manual training annotation nor physical marking. AMADEUS extracts masks representing single animals, uses movement direction to assign head direction, and then synthesizes interaction images using copy-paste augmentation. A detector trained on the synthetic dataset estimates oriented bounding boxes and head direction, from which center, front and rear keypoints are derived. For a video containing instances of almost complete occlusion, AMADEUS additionally uses contrastive learning for identity verification. Across benchmark videos of 10 mice, 10 fish, 32 beetles, 32 ants with one cricket, 60 flies, and 368 ants, AMADEUS outperformed state-of-the-art methods in identity tracking and keypoint localization. AMADEUS enables scalable quantification of interactions across diverse species.

animal behavior and cognition↗

Associations between striatal neurochemical changes and resting-state functional connectivity following transcranial temporal interference stimulation

Background Non-invasive modulation of deep brain structures remains a major challenge in human neuroscience and neurorehabilitation. Transcranial temporal interference stimulation (tTIS) has emerged as a promising approach for engaging subcortical regions, but its effects on striatal neurochemical markers and functional connectivity remain unclear. Objective To investigate whether 20-Hz tTIS designed to target the right striatum modulates GABA+ and glutamate-glutamine complex (Glx) levels and whether neurochemical changes are associated with changes in resting-state functional connectivity. Methods Thirty-four healthy right-handed participants were randomly assigned to the tTIS group (20-Hz beat frequency) or sham group (0-Hz frequency difference). Participants underwent proton magnetic resonance spectroscopy (1H-MRS) and resting-state fMRI before and after 30 min of stimulation. One participant in the tTIS group was excluded from the 1H-MRS analyses because of data corruption. Results The direct between-group difference in Glx change did not reach statistical significance, although the tTIS group showed a numerically greater reduction than the sham group (p = 0.066). Exploratory within-group analyses showed a significant decrease in striatal Glx in the tTIS group (p < 0.001), whereas the decrease in the sham group was not significant. No significant GABA+ changes were observed within or between groups. The association between striatal Glx change and functional connectivity change differed between groups in the sensorimotor cortex, right parahippocampal gyrus, and bilateral fusiform gyri. Conclusion These exploratory findings suggest that 20-Hz tTIS may be associated with striatal Glx modulation and group-dependent coupling between neurochemical and cortico-subcortical network changes.

neuroscience↗

Tumor Microenvironment Modulates Lineage Plasticity in Lung Squamous Cell Carcinoma

Lung squamous cell carcinoma (LUSC) is the second most common type of lung cancer, yet therapeutic options remain limited. A deeper understanding of its biology and molecular pathogenesis is essential for developing new treatment strategies. Here, we investigated the mechanisms of phenotypic plasticity in LUSC by comparing organoid-derived orthotopic lung models (ODOLs) and subcutaneous xenograft models (ODXs). ODXs showed greater tumor growth, squamous differentiation, and extracellular matrix (ECM) organization compared to ODOLs. Transcriptomic analyses revealed upregulation of multiple HIF1 and SOX2 target genes together with enhanced hypoxia signaling in ODXs. CRISPR/Cas9-mediated HIF1-knockout ODXs showed reduced SOX2 expression, tumor growth, and ECM organization, whereas SOX2-knockout ODXs reduced tumor growth without affecting HIF1 and ECM organization. These results indicate that HIF1 regulates squamous lineage maintenance through SOX2 and ECM remodeling. Spatial transcriptomics revealed enrichment of basal cell-like and squamous-differentiated tumor states in ODXs, whereas ODOLs displayed less differentiated phenotypes. These findings identify the tumor microenvironment as a critical determinant of lineage plasticity in LUSC and provide mechanistic insight into how hypoxia shapes tumor differentiation.

Cancer Biology↗

Enkephalin Gates D2-MSN Disinhibition of the Ventral Pallidum During Cocaine Abstinence

Background: Cocaine seeking after abstinence is associated with increased ventral pallidum (VP) activity. This increase appears to involve an opioid peptide that suppresses GABA release from D2 receptor-expressing medium spiny neurons (D2-MSNs) to the VP, but its identity is unclear. We previously found that cocaine abstinence increases enkephalin mRNA expression in D2-MSNs and that exogenous enkephalin inhibits GABA release from these neurons. We therefore hypothesized that cocaine-enhanced enkephalin release from D2-MSNs suppresses GABA release into the VP, which disinhibits VP neurons and promotes cocaine seeking. Methods: To examine how enkephalin alters striatal circuit plasticity and cocaine seeking following abstinence, we performed ex vivo electrophysiology and cocaine self-administration in mice lacking enkephalin selectively from D2-MSNs (D2-PenkKO). Recordings were obtained from the primary D2-MSNs targets : VP neurons and D1 receptor-expressing MSNs (D1-MSNs). Results: Following cocaine abstinence, GABA release from D2-MSNs to VP neurons was reduced in controls, but not D2-PenkKOs. In contrast, cocaine abstinence did not alter GABA release to D1-MSNs. Optogenetically evoked GABA release from D2-MSNs inhibited VP neuron firing in saline-abstinent controls and D2-PenkKOs, but not cocaine-abstinent controls. Female, but not male, D2-PenkKOs self-administered less cocaine in early acquisition and exhibited blunted cue-induced cocaine seeking after abstinence. Conclusion: Abstinence from cocaine self-administration increases D2-MSN enkephalin expression, leading to auto-inhibition of GABA release onto VP neurons, but not D1-MSNs, thereby selectively disinhibiting VP neuron activity. These findings identify enkephalin as a key mediator of cocaine abstinence-induced striatopallidal circuit plasticity and suggest that this plasticity contributes to cocaine seeking following abstinence.

neuroscience↗

Transcutaneous vagus nerve stimulation reduces total striatal GABA content and facilitates early-phase motor learning

BackgroundTranscutaneous vagus nerve stimulation (tVNS) has emerged as a promising non-invasive technique for modulating neuroplasticity. Previous studies have suggested that changes in regional brain GABA signaling contribute to these effects, but empirical neurophysiological evidence remains limited. MethodsWe investigated the neurophysiological and behavioral effects of tVNS (200-s pulses at 20 Hz, alternating 30 s ON-1 s OFF cycles, 30 min total duration) in healthy adults using two experimental paradigms. In Experiment 1, GABA levels were measured in the left striatum (STR), dorsolateral prefrontal cortex (DLPFC), and sensorimotor cortex (SM) of 34 participants by magnetic resonance spectroscopy (MRS) before and after ipsilateral tVNS. In Experiment 2, 28 participants performed a right-hand force-control motor learning task before, during, and after tVNS. ResultsAdministration of tVNS significantly reduced GABA levels in the left STR compared to sham stimulation (p < 0.05), and also significantly improved motor task performance compared to the sham group at 10 minutes after stimulus onset (p < 0.05) ConclusionTranscutaneous VNS may facilitate early-phase motor learning by reducing striatal GABA levels and consequently inducing corticobasal circuit disinhibition. These findings support tVNS as a potential noninvasive intervention to enhance motor learning for neurorehabilitation and motor disorder treatment.

neuroscience↗

Wakeful targeted memory reactivation during short rest periods modulates motor learning via the lateral orbitofrontal cortex network

This study investigated whether wakeful targeted memory reactivation (TMR) during short rest intervals improves motor learning. Participants were randomly assigned to the following four groups and performed a sequential key-press task under each condition: (1) TMRno group: no auditory stimuli, (2) TMRregular group: auditory cues played at the same speed as the previous task, (3) TMRfast group: auditory cues played 1.3 times faster, and (4) TMRrandom group: auditory cues randomized in pitch. The TMRregular group suppressed early learning gains compared with the TMRno and TMRfastgroups. Electroencephalogram revealed reduced functional connectivity centered on the lateral orbitofrontal cortex (lOFC) in the TMRregular group. In contrast, the TMRfastgroup preserved early learning and exhibited improved lOFC-centered functional connectivity compared with the TMRregulargroup. Therefore, wakeful TMR might either hinder or support motor learning, depending on cue timing and structure, emphasizing the need to optimize sensory parameters for effective learning improvement.

neuroscience↗

C57 and DBA mouse strains express distinct cocaine avoidance phenotypes in an operant runway independent of differences in striatal dynorphin-enkephalin balance

RationaleHuman self-report data and rodent models indicate cocaine can induce negative affect, which may impact future cocaine use severity. Despite this, understanding of the neurobiology driving cocaine avoidance is limited. Within the striatum, the opioid peptides enkephalin and dynorphin are associated with cocaine reward and aversion, respectively. Additionally, striatal dynorphin signaling resulting from stress or cocaine withdrawal acts as a negative reinforcer to increase cocaine seeking. ObjectivesWe validated the use of the cocaine self-administration runway in mice to measure the development of cocaine avoidance and tested whether mice with higher relative striatal dynorphin-to-enkephalin expression are resistant to developing cocaine avoidance. MethodsCocaine avoidance in the self-administration runway was measured in two inbred mouse strains, C57BL/6J and DBA/2J, known to have opposite striatal dynorphin/enkephalin milieus, and in mice lacking enkephalin selectively from striatal medium spiny neurons (D2-PenkKO). ResultsBoth inbred strains developed cocaine avoidance, though they expressed it differently. Across training, DBA/2J mice increased their latency to self-administer cocaine, and C57BL/6J increased the number of retreats away from the cocaine-paired goal box. D2-PenkKOs developed similar cocaine avoidance compared to littermate controls. ConclusionsMice develop avoidance to self-administer cocaine in the runway across a range of strains. Pre-existing strain differences in the striatal dynorphin/enkephalin milieu, however, do not appear to alter the development of cocaine avoidance, and striatal enkephalin is not necessary for the development of cocaine avoidance. This suggests higher relative striatal dynorphin does not facilitate cocaine seeking by mitigating cocaine avoidance.

neuroscience↗

No association between metabolic rate and an exaggerated sexually selected trait

Exaggerated sexually selected traits are thought to be energetically costly to produce and to maintain. This is especially true of sexually selected weapons, traits that are frequently positively allometric, and therefore likely to be especially energetically costly. However, there have been few studies that directly measure these putative costs. Additionally, metabolic rate, a measure of energy expenditure, is highly variable across individuals, but the causes of this variation are not always well established. Here we tested for the associations between resting metabolic rate, during development and adulthood, and the size of a weapon used during adult male-male competition in the beetle Gnatocerus cornutus. We also tested for genetic variation metabolic rate and weapon size. We found that metabolic rate was not statistically associated with weapon size, but there were effects of genotype and mass during development (pupal size) on weapons. Additionally, age, mass and genotype all affected metabolic rate in various ways. Despite no evidence of energetic costs to weapon development or maintenance, direct predation costs associated with them have been detected previously, and hence enlarged weapons are costly in this system. Significance statementThe large weapons used in competition between males are thought to be energetically costly. However, there are rather few investigations of these putative costs. We investigate these potential costs by testing for associations between metabolic rate and weapon size in a beetle. We found no relationship between weapons and metabolism, indicating weapons are not always energetically costly.

ecology↗

Ancient genomics support deep divergence between Eastern and Western Mediterranean Indo-European languages

The Indo-European languages are among the most widely spoken in the world, yet their early diversification remains contentious1-5. It is widely accepted that the spread of this language family across Europe from the 5th millennium BP correlates with the expansion and diversification of steppe-related genetic ancestry from the onset of the Bronze Age6,7. However, multiple steppe-derived populations co-existed in Europe during this period, and it remains unclear how these populations diverged and which provided the demographic channels for the ancestral forms of the Italic, Celtic, Greek, and Armenian languages8,9. To investigate the ancestral histories of Indo-European-speaking groups in Southern Europe, we sequenced genomes from 314 ancient individuals from the Mediterranean and surrounding regions, spanning from 5,200 BP to 2,100 BP, and co-analysed these with published genome data. We additionally conducted strontium isotope analyses on 224 of these individuals. We find a deep east-west divide of steppe ancestry in Southern Europe during the Bronze Age. Specifically, we show that the arrival of steppe ancestry in Spain, France, and Italy was mediated by Bell Beaker (BB) populations of Western Europe, likely contributing to the emergence of the Italic and Celtic languages. In contrast, Armenian and Greek populations acquired steppe ancestry directly from Yamnaya groups of Eastern Europe. These results are consistent with the linguistic Italo-Celtic10,11 and Graeco-Armenian1,12,13 hypotheses accounting for the origins of most Mediterranean Indo-European languages of Classical Antiquity. Our findings thus align with specific linguistic divergence models for the Indo-European language family while contradicting others. This underlines the power of ancient DNA in uncovering prehistoric diversifications of human populations and language communities.

genetics↗

Striatal enkephalin supports maintenance of conditioned cocaine reward during extinction

Drug predictive cues and contexts exert powerful control over behavior and can incite drug seeking and taking. This association and the behavioral output are encoded within striatal circuits, and regulation of these circuits by G-protein coupled receptors affects cocaine-related behaviors. Here, we investigated how opioid peptides and G-protein coupled opioid receptors expressed in striatal medium spiny neurons (MSNs) regulate conditioned cocaine seeking. Augmenting levels of the opioid peptide enkephalin in the striatum facilitates acquisition of cocaine conditioned place preference (CPP). In contrast, opioid receptor antagonists attenuate cocaine CPP and facilitate extinction of alcohol CPP. However, whether striatal enkephalin is necessary for acquisition of cocaine CPP and maintenance during extinction remains unknown. We generated mice with a targeted deletion of enkephalin from dopamine D2-receptor expressing MSNs (D2-PenkKO) and tested them for cocaine CPP. Low striatal enkephalin levels did not attenuate acquisition or expression of CPP; however, D2-PenkKOs showed faster extinction of cocaine CPP. Single administration of the non-selective opioid receptor antagonist naloxone prior to preference testing blocked expression of CPP selectively in females, but equally between genotypes. Repeated administration of naloxone during extinction did not facilitate extinction of cocaine CPP for either genotype, but rather prevented extinction in D2-PenkKO mice. We conclude that while striatal enkephalin is not necessary for acquisition of cocaine reward, it maintains the learned association between cocaine and its predictive cues during extinction learning. Further, sex and pre-existing low striatal enkephalin levels may be important considerations for use of naloxone in treating cocaine use disorder.

neuroscience↗

Dystroglycan N-terminal domain enables LARGE1 to extend matriglycan on α-dystroglycan and prevents muscular dystrophy

Dystroglycan (DG) requires extensive post-translational processing to function as a receptor for extracellular matrix proteins containing laminin-G-like (LG) domains. Matriglycan is an elongated polysaccharide of alternating xylose and glucuronic acid that is uniquely synthesized on -dystroglycan (-DG) by like-acetylglucosaminyltransferase-1 (LARGE1) and binds with high affinity to matrix proteins like laminin. Defects in the post-translational processing of -DG that result in a shorter form of matriglycan reduce the size of -DG and decrease laminin binding, leading to various forms of muscular dystrophy. However, little is known regarding mechanisms that generate full-length matriglycan on -DG (~150-250 kDa). Here, we show that LARGE1 can only synthesize a short, non-elongated form of matriglycan in mouse skeletal muscle that lacks the DG N-terminus (-DGN), resulting in a ~100-125 kDa -DG. This smaller form of -DG binds laminin and maintains specific force but does not prevent muscle pathophysiology, including reduced force induced by eccentric contractions and abnormalities in neuromuscular junctions. Collectively, our study demonstrates that -DGN is required for LARGE1 to extend matriglycan to its full mature length on -DG and thus prevent muscle pathophysiology.

biochemistry↗

Genes responsible for avoiding attack of a beetle, relating to the duration of death feigning

Predator avoidance is an important behavior that affects the degree of adaptation of organisms. We compared the DNA variation of one of the predator-avoidance behaviors, the recently extensively studied "death-feigning behavior," between the long strain bred for feigning death for a long time and the short strain bred for feigning death for a short time. To clarify how the difference in DNA sequences between the long and short strains corresponds to the physiological characteristics of the death-feigning duration at the transcriptome level, we performed comprehensive and comparative analyses of gene variants in Tribolium castaneum strains using DNA-re-sequence. The duration of death feigning involves many gene pathways, including caffeine metabolism, tyrosine metabolism, tryptophan metabolism, metabolism of xenobiotics by cytochrome P450, longevity regulating pathways, and circadian rhythm. Artificial selection based on the duration of death feigning results in the preservation of variants of genes in these pathways in the long strain. When an animal wake up from a near-death experience is closely related to its success in avoiding predation. This study suggests that many metabolic pathways and related genes may be involved in the decision-making process of anti-predator animal behavior by forming a network in addition to the tyrosine metabolic system, including dopamine, revealed in previous studies.

animal behavior and cognition↗

Polygene control and trait dominance in death-feigning syndrome in the red flour beetle Tribolium castaneum

Death-feigning behavior is an anti-predator behavior in a wide range of animal taxa, and it often correlates with the movement (i.e. death-feigning syndrome). In the present study, we performed reciprocal crossing among strains with genetically longer (L strain) and shorter (S strain) duration of death feigning, and investigated related heritable factors in the F1 and F2 populations. We also investigated moving activity which negatively responded to artificial selection for death feigning in T. castaneum. Our results showed that death feigning occurred more frequently and for shorter periods in the F1 population. In the F2 population, death feigning and movement showed continuous segregation. The distribution of each trait value in the F2 generation was different from the distribution of trait values in the parental generation, and no individuals transgressing the distribution of trait values in the parental generation emerged in the F2 generation. Chi-square analysis of the observed death feigning and movement of F1 and F2 progenies rejected the hypothesis of mono-major gene inheritance. These results suggest that death-feigning syndrome is controlled in a polygenic manner. Our study indicated that reciprocal crossing experiments are useful in assessing the quantitative inheritance of behavioral traits.

evolutionary biology↗

Amplitude of circadian rhythms becomes weaker in the north, but there is no cline in the period of rhythm in a beetle

Many species show rhythmicity in activity, from the timing of flowering in plants to that of foraging behaviour in animals. The free-running periods and amplitude (sometimes called strength or power) of circadian rhythms are often used as indicators of biological clocks. Many reports have shown that these traits highly geographically variable, and interestingly, they often show latitudinal or altitudinal clines. In many cases, the higher the latitude is, the longer the free-running circadian period (i.e., period of rhythm) in insects and plants. However, reports of positive correlations between latitude or longitude and circadian rhythm traits, including free-running periods, the power of the rhythm and locomotor activity, are limited to certain taxonomic groups. Therefore, we collected a cosmopolitan stored-product pest species, the red flour beetle Tribolium castaneum, in various parts of Japan and examined its rhythm traits, including the power of the rhythm and period of the rhythm, which were calculated from locomotor activity. The analysis revealed that power was significantly lower for beetles collected in northern areas compared with southern areas in Japan. However, it is worth noting that the period of circadian rhythm did not show any clines; specifically, it did not vary among the sampling sites, despite the very large sample size (n = 1585). We discuss why these cline trends were observed in T. castaneum.

animal behavior and cognition↗

Is there a genetic correlation between movement and immobility in field populations of a beetle?

Genetic correlations among behavioural traits are often controlled by pleiotropic genes. Many studies suggest the existence of genetic correlations among behavioural traits based on artificial selection experiments in the laboratory. However, few studies have examined whether behavioural correlations in the laboratory are maintained in the field, where natural selection works. Artificial selection experiments showed a behavioural correlation among death feigning, walking movement, and locomotor activity in the red flour beetle (Tribolium castaneum). This study investigated whether this behavioural correlation is observed in wild T. castaneum populations. We also collected beetles from various regions in Japan and investigated the geographic variation in these traits. There was geographic variation in the three behavioural traits. However, these behavioural traits were not correlated. The results suggest that the genetic correlations among behavioural traits are not maintained in the field. Therefore, the results derived from laboratory experiments may be overestimated. The same correlation between traits was not believed to arise in the field, as the indoor results may have been caused by unrealistic selection pressures. Further laboratory and field investigations are both needed.

animal behavior and cognition↗

Mechanism of hERG inhibition by gating-modifier toxin, APETx1, deduced by functional characterization

Human ether-a-go-go-related gene potassium channel 1 (hERG) is a voltage-gated potassium channel, the voltage-sensing domain (VSD) of which is targeted by a gating-modifier toxin, APETx1. Although it is known that APETx1 inhibits hERG by stabilizing the resting state, it remains unclear where and how APETx1 interacts with the VSD in the resting state. Here, we prepared a recombinant APETx1, which is structurally and functionally equivalent to the natural product. Electrophysiological analyses using wild type and mutants of APETx1 and hERG revealed that their hydrophobic residues, in addition to a previously reported acidic hERG residue, play key roles in the inhibition of hERG by APETx1. Docking models of the APETx1-VSD complex that satisfy the results of mutational analysis suggest a molecular recognition mode between APETx1 and the resting state of hERG; this would provide a structural basis for designing ligands that control hERG function by binding to the VSD.

molecular biology↗

Dose old age lead to gluttony? Effects of aging on predation and locomotion in the assassin bug Amphibolus venator.

Animal behaviors are often affected by aging. In many insect species, locomotor activity decreases with aging. Foraging ability may also decrease with aging. However, few studies have investigated the effects of aging on both locomotor activity and foraging ability. In the present study, we tested the aging effect on locomotor activity and foraging ability in the assassin bug Amphibolus venator. The present results showed that locomotor activity decreased with age, similar to findings in many other animal species. However, foraging ability increased with age. Namely, the decline in locomotor activity with age did not lead to a decline in foraging ability. The positive relationship between foraging ability and age may be related to the type of predation, sit-and-wait, used by A. venator via alterations in investment in reproductive traits with age.

animal behavior and cognition↗