Biology subjects

Matsuzaki, M.

Publications and source records attributed to Matsuzaki, M..

16 recordsLinked to original sources

bioRxiv2026

Pan-cortical area sensorimotor network coordination during motor learning of forelimb-reaching task in the marmoset

Motor learning alters activities in multiple brain areas. While learning-induced activity change in these areas has been investigated, how the information flow changes in the network across those areas remains to be thoroughly examined. We analysed wide-field calcium imaging data spanning from the premotor cortex to the parietal cortex of marmosets while they learned a two-target forelimb-reaching task. We applied non-negative matrix factorization (NMF) to the activity data and extracted about 30 localized activity components. Encoding model analysis indicated that learning was associated with a decrease in activity components related to hand movements, and an increase in those related to external and reward signals. Causality analysis by embedding entropy (EE) revealed increases in causal links across activity components in different areas and stabilization of the network structure with behavioural improvements. These results indicate that motor learning entails both a redistribution of task-related activity and a reorganization of large-scale cortical network interactions.

neuroscience↗

bioRxiv2025

Blockade of associative spine enlargement impairs awake cortical function

Awake cognition is usually attributed to arousal systems and ongoing electrical activity, yet these do not explain how cortical processing is coupled to prior context and memory formation. Associative synaptic plasticity provides a cellular mechanism for such coupling, but is viewed as memory-related rather than an online requirement for cognition. Here we developed SynC, an A/C-activated chemogenetic perturbation that selectively and reversibly blocks associative spine enlargement while sparing non-associative spine dynamics, excitability, synaptic transmission and NMDA receptor-mediated responses. In mice with broad frontoparietal SynC expression, acute A/C reversibly impaired open-field centre exploration, abolished laser-dot chasing, and delayed feeding initiation. During quiet-wake immobile epochs, cortical firing rates and {gamma}-band power were preserved, but pairwise spike correlations were reduced. Mice also intermittently showed sudden behavioural arrest with reduced {gamma} activity but without the robust {delta} elevation of slow-wave sleep. Critically, in vivo two-photon glutamate uncaging induced seconds-scale associative spine enlargement in [~]24% of neocortical spines, acutely blocked by SynC-A/C. These A/C-induced behavioural, circuit and spine-enlargement effects recovered within 1 h. Thus, wake-like firing and {gamma} activity are not sufficient to sustain awake cognitive function. Rapid associative spine enlargement is required to maintain functional cortical coupling and stable wakefulness.

neuroscience↗

bioRxiv2025

A multimodal dataset linking wide-field calcium imaging to behavior changes in mice during an operant lever-pull task

The BraiDyn-BC (Brain Dynamics underlying emergence of Behavioral Change) Database offers an extensive, multimodal dataset that links wide-field calcium imaging of the mouse neocortex to comprehensive behavioral measurements during a behavioral task. As one of the contents in this database, we newly provide a dataset that includes 15 sessions spanning two weeks of motor skill learning, in which 25 mice were trained to pull a lever to obtain water rewards. Simultaneous high-speed videography captures body, facial, and eye movements, and environmental parameters are monitored. The dataset also features resting-state cortical activity and sensory-evoked responses, enhancing its utility for both learning-related and sensory-driven neural dynamics studies. Data are formatted in accordance with the Neurodata Without Borders (NWB) standard, ensuring compatibility with existing analysis tools and adherence to the FAIR principles. This resource enables in-depth investigations into the neural mechanisms underlying behavior and learning. The platform encourages collaborative research, supporting the exploration of rapid within-session learning effects, long-term behavioral adaptations, and neural circuit dynamics.

neuroscience↗

bioRxiv2025

A cell-matrix interaction regulates the undifferentiated state and self-renewal capacity of avian primordial germ cells

Primordial germ cells (PGCs) are lineage restricted precursor cells of sperm and eggs. Whilst avian PGCs from chicken can be cultured and modified to produce genome-edited chickens, the long-term culture of PGCs from other bird species has not been achieved. Here, we explored the effects of a cell-matrix interaction on the in vitro propagation of chicken PGCs. Blocking integrin signaling severely reduced the self-renewal of the PGC, indicating that a PGC-matrix interaction is an essential process for self-renewal. We investigated the properties of somatic cell differentiated PGCs and expression analyses suggested that the PGCs undergo a partial epithelial-to-mesenchymal transition caused by excess PGC-matrix interactions. Finally, we conducted a long-term culture of chicken PGCs with matrix components, resulting in significant induction of their somatic conversion. These results suggested that a high level of PGC-matrix interaction can cause somatic conversion, whilst a moderate level is essential for their proliferation. Overall, we identified a molecular aspect of self-renewal and maintaining undifferentiated states of avian PGCs.

developmental biology↗

bioRxiv2024

Movement-independent representation of reward-predicting cues in the medial part of the primate premotor cortex

Neural activity across the dorsal neocortex of rodents is dominated by orofacial and limb movements, irrespective of whether the movements are task-relevant or task-irrelevant. To examine the extent to which movements and a primitive cognitive signal, i.e., reward expectancy, modulate the activity of multiple cortical areas in primates, we conducted unprecedented wide-field one-photon calcium imaging of frontoparietal and auditory cortices in common marmosets while they performed a classical conditioning task with two auditory cues associated with different reward probabilities. Licking, eye movement, and hand movement strongly modulated the neuronal activity after cue presentation in the motor and somatosensory cortices in accordance with the somatotopy. By contrast, the posterior parietal cortex and primary auditory cortex did not show much influence from licking. Licking increased the activity in the caudal part of the dorsal premotor cortex, but decreased the activity in the central and lateral parts of the rostral part of the dorsal premotor cortex (PMdr). Reward expectancy that was separable from both spontaneous and goal-directed movements was mainly represented in the medial part of PMdr. Our results suggest that the influence of movement on primate cortical activity varies across areas and movement types, and that the premotor cortex processes motor and cognitive information in different ways within further subdivided areas.

neuroscience↗

bioRxiv2024

ARViS: A bleed-free multi-site automated injection robot for accurate, fast, and dense delivery of virus to mouse and marmoset brains

Genetically encoded fluorescent sensors continue to be developed and improved. If they could be expressed across multiple cortical areas in non-human primates, it would be possible to measure a variety of spatiotemporal dynamics of primate-specific cortical activity. Here, we develop an Automated Robotic Virus injection System (ARViS) for broad expression of a biosensor. ARViS consists of two technologies: image recognition of vasculature structures on the cortical surface to determine multiple injection sites without hitting them, and robotic control of micropipette insertion perpendicular to the cortical surface with 50-m precision. In mouse cortex, ARViS sequentially injected virus solution into 100 sites over a duration of 100-minutes with a bleeding probability of only 0.1% per site. Furthermore, ARViS successfully achieved 266-site injections over the frontoparietal cortex of a common marmoset. We demonstrate one-photon and two-photon calcium imaging in the marmoset frontoparietal cortex, illustrating the effective expression of biosensors delivered by ARViS.

neuroscience↗

bioRxiv2024

Medial prefrontal cortex suppresses reward-seeking behavior with risk of positive punishment by reducing sensitivity to reward

Reward-seeking behavior is frequently associated with risk of punishment. There are two types of punishment: positive, resulting in an unpleasant outcome, and negative, resulting in omission of a reinforcing outcome. Although the medial prefrontal cortex (mPFC) is important in avoiding punishment, whether it is important for avoiding both positive and negative punishment and how it contributes to such avoidance are not clear. In this study, we trained male mice to perform decision-making tasks under the risks of positive (air-puff stimulus) and negative (reward omission) punishment. We found that pharmacological inactivation of mPFC enhanced the reward-seeking choice under the risk of positive, but not negative, punishment. In reinforcement learning models, this behavioral change was well-explained by hypersensitivity to the reward, rather than a decrease in the strength of aversion to punishment. Our results suggest that mPFC suppresses reward-seeking behavior by reducing sensitivity to reward under the risk of positive punishment.

animal behavior and cognition↗

bioRxiv2023

Dynamics of motor direction representation in the primate premotor and primary motor cortices during sensorimotor learning

Sensorimotor learning requires reorganization of neuronal activity in the premotor cortex (PM) and primary motor cortex (M1). However, how PM- and M1-specific reorganization occurs in primates remains unclear. We conducted calcium imaging of these areas in common marmosets while they learned a two-target reaching (pull/push) task. Throughout learning, the dorsorostral PM (PMdr) showed peak activity earlier than the dorsocaudal PM (PMdc) and M1. PMdr showed decreased representation of newly introduced (push) movement, whereas PMdc and M1 maintained high representation. Many task-related neurons in PMdc and M1 exhibited a strong preference to either movement direction. PMdc neurons dynamically switched their preferred direction, whereas M1 neurons stably retained their preferred direction. Differences in preferred direction between adjacent neurons in PMdc increased during learning. These results suggest that in primate sensorimotor learning, dynamic motor representation in PMdc converts the cognitive sensorimotor signals of PMdr to stable and specific motor representation of M1.

neuroscience↗

bioRxiv2023

Negative reward-prediction errors of climbing fiber inputs for cerebellar reinforcement learning algorithm

Although the cerebellum is typically linked to supervised learning algorithms, it also exhibits extensive involvement in reward processing. In this study, we investigated the cerebellums role in executing reinforcement learning algorithms, with a particular emphasis on essential reward-prediction errors. We employed the Q-learning model to accurately reproduce the licking responses of mice in a Go/No-go auditory-discrimination task. This method enabled the calculation of reinforcement learning variables, such as reward, predicted reward, and reward-prediction errors in each learning trial. By tensor component analysis of two-photon Ca2+ imaging data from more than 6,000 Purkinje cells, we found that climbing fiber inputs of the two distinct components, which were specifically activated during Go and No-go cues in the learning process, showed an inverse relationship with predictive reward-prediction errors. By assuming bidirectional parallel-fiber Purkinje-cell synaptic plasticity, we constructed a cerebellar neural-network model with 5,000 spiking neurons of granule cells, Purkinje cells, cerebellar nuclei neurons, and inferior olive neurons. The network model qualitatively reproduced distinct changes in licking behaviors, climbing-fiber firing rates and their synchronization during discrimination learning separately for Go/No-go conditions. We found that Purkinje cells in the two components could develop specific motor commands for their respective auditory cues, guided by the predictive reward-prediction errors from their climbing fiber inputs. These results indicate a possible role of context-specific actors in modular reinforcement learning, integrating with cerebellar supervised learning capabilities.

neuroscience↗

bioRxiv2022

Dynamic organization of cerebellar climbing fiber response and synchrony in multiple functional modules reduces dimensions for reinforcement learning

Daynamic functional organization by synchronization is theorized to be essential for dimension reduction of the cerebellar learning space. We analyzed a large amount of coordinate-localized, two-photon imaging data from cerebellar Crus II in mice undergoing "Go/No-go" reinforcement learning. Tensor component analysis revealed that a majority of climbing fiber inputs to Purkinje cells were reduced to only four functional components, corresponding to accurate timing control of motor initiation related to a Go cue, cognitive error-based learning, reward processing, and inhibition of erroneous behaviors after a No-go cue. Spatial distribution of these components coincided well with the boundaries of Aldolase-C/zebrin II expression in Purkinje cells, whereas several components are mixed in single neurons. Synchronization within individual components was bidirectionally regulated according to specific task contexts and learning stages. These findings suggest that the cerebellum, based on anatomical compartments, reduces dimensions by self-organization of components, a feature that may inspire new-generation AI designs.

neuroscience↗

bioRxiv2022

Screening of the optimal CpG-oligodeoxynucleotide for anti-inflammatory responses in avian macrophage cell line HD11

CpG-oligodeoxynucleotides (CpG-ODN) has been shown to possess immunostimulatory features in both mammals and birds. However, compared to its pro-inflammatory effects, little is known about the anti-inflammatory responses triggered by CpG-ODN in avian cells. Hence, in this study, we aimed to characterize the anti-inflammatory response in the chick macrophage cell line HD11 under the stimulation of five kinds of CpG-ODN: CpG-A1585, CpG-AD35, CpG-B1555, CpG-BK3, and CpG-C2395. Single-stimulus CpG-B1555, CpG-BK3, and CpG-C2395 induced the interleukin (IL)-10 expression without causing cellular injury. The effects of pretreatment with each CpG-ODN before subsequent lipopolysaccharide stimulation were also evaluated. Interestingly, only CpG-C2395 maintained a high expression level in this situation. Finally, expression analysis of inflammation-related genes, such as the tumor necrosis factor-, IL-1{beta}, IL-6, and Toll-like receptor 4, was conducted, and pretreatment with CpG-C2395 significantly reduced their expression. Overall, our results shed light on the anti-inflammatory responses triggered by CpG-C2395 stimulation using a comparative analysis of three major classes of CpG-ODN in chick macrophages.

immunology↗

bioRxiv2022

Prediction of sex-determination mechanisms in avian primordial germ cells using RNA-seq analysis

Avian sex is determined by various factors, such as the dosage of DMRT1 and cell-autonomous mechanisms. While the sex-determination mechanism in gonads is well analyzed, the mechanism in germ cells remains unclear. In this study, we explored the gene expression profiles of male and female primordial germ cells (PGCs) during embryogenesis in chickens to predict the mechanism of sex-determination. Male and female PGCs were isolated from blood and gonads with a purity > 96% using flow cytometry and analyzed using RNA-seq. Prior to settlement in the gonads, female circulating PGCs (cPGCs) obtained from blood displayed sex-biased expression. Gonadal PGCs (gPGCs) also displayed sex-biased expression, and the number of female-biased genes detected was higher than male-biased genes. The female-biased genes in gPGCs were enriched in some metabolic processes. To reveal the mechanisms underlying the transcriptional regulation of female-biased genes in gPGCs, we performed stimulation tests. Stimulation with retinoic acid against cultured gPGCs derived from male embryos resulted in the upregulation of several female-biased genes. Overall, our results suggest that sex determination of avian PGCs possess aspects of both cell-autonomous and somatic cell regulation. Moreover, it appears that sex determination occurs earlier in females than in males.

developmental biology↗

bioRxiv2020

Independent representations of reward-predicting cues and reward history in frontal cortical neurons

The transformation of sensory inputs to appropriate goal-directed actions requires estimation of sensory-cue values based on outcome history. To clarify how cortical neurons represent an outcome-predicting cue and actual outcome, we conducted wide-field and two-photon calcium imaging of the mouse neocortex during performance of a classical conditioning task with two cues with different water-reward probabilities. Although licking behavior dominated the area-averaged activity over the whole dorsal neocortex, dorsomedial frontal cortex (dmFrC) affected other dorsal frontal cortical activities, and its inhibition extinguished differences in anticipatory licking between the cues. In individual frontal cortical neurons, the reward-predicting cue was not simultaneously represented with the current or past reward, but licking behavior was frequently multiplexed with the reward-predicting cue and current or past reward. Deep-layer neurons in dmFrC most strongly represented the reward-predicting cue and recent reward history. Our results suggest that these neurons ignite the cortical processes required to select appropriate actions.

neuroscience↗

bioRxiv2019

Endogenization and excision of human herpesvirus 6 in human genomes

The genome of human herpesvirus 6 (HHV-6) is integrated within the nuclear genome of about 1% of humans, but how this came about is not clear. HHV-6 integrates into telomeres, and this has recently been associated with polymorphisms affecting MOV10L1. MOV10L1 is located on the subtelomere of chromosome 22q (chr22q) and is required to make PIWI-interacting RNAs (piRNAs). piRNAs block integration of transposons in the germline, so piRNA-mediated repression of HHV-6 integration has been suspected. Whether integrated HHV-6 can reactive into an infectious virus is also uncertain. In vitro, recombination of the viral genome along its terminal direct repeats (DRs) leads to excision from the telomere and viral reactivation, but the expected single DR "scar" has not been described in vivo. We analyzed whole-genome sequencing (WGS) data from 13,040 subjects, including 7,485 from Japan. We found an association between integrated HHV-6 and polymorphisms on chr22q in Japanese subjects. However, association with the reported MOV10L1 polymorphism was driven by physical linkage to a single ancient endogenous HHV-6A variant integrated into the telomere of chr22q in East Asians. We resolved the junction of the human chromosome with this viral genome using long read sequencing. Unexpectedly, an HHV-6B variant has also endogenized in chr22q; two endogenous HHV-6 variants at this locus thus account for 72% of all integrated HHV-6 in Japan. We also report human genomes carrying only one portion of the HHV-6B genome, a single DR, supporting in vivo excision and viral reactivation. Using WGS data from North American families, we show that the incidence of HHV-6 integration into the germline is lower than its prevalence, and that integrated HHV-6 is not associated with the reported variant in MOV10L1. Together these results explain the recently reported association between integrated HHV-6 and MOV10L1/piRNAs, suggest exaptation of HHV-6 in its coevolution with human chr22q, and clarify the evolution and risk of reactivation of the only intact non-retroviral genome known to be present in human germlines. SIGNIFICANCE STATEMENT Human herpesvirus 6 (HHV-6) infects most people during childhood, usually only causing fever and rash. Reactivation of HHV-6 has been linked to a number of neurological diseases including encephalitis, Alzheimers disease and multiple sclerosis. However, about 1% of people are born with the HHV-6 genome present within their genome, included in the end "cap" of one of their 46 chromosomes. Little is known about how and when HHV-6 genomes entered human genomes, whether or not they still do, and whether or not this poses risk for virus reactivation. We looked for HHV-6 in genome sequences from over 13,000 people. Most HHV-6 variants present in human genomes have been co-evolving with human chromosomes for many generations, and new integration events are rare. Surprisingly, in almost three fourths of Japanese people with HHV-6 in their genome, HHV-6 integrated in the same end of the same chromosome - 22q. Persistence of the HHV-6 genome within the short "cap" that preserves the end of chromosome 22q suggests that the integrated viral sequence may have taken on a useful function for this chromosome. We also found that some human genomes harbor only one part of the HHV-6 genome. This part is the same part that remains after experimental viral reactivation, during which most of the virus is cut out of the genome. This warrants assessment of the risk that integration of HHV-6 into inherited human genomes is not irreversible, and possibly leads to production of infectious virus.

genetics↗

bioRxiv2019

Fast and accurate defocus for improved tunability of cryo-EM experiments

Current data collection strategies in electron cryo-microscopy (cryo-EM) record multiframe movies with static optical settings. This limits the number of adjustable parameters that can be used to optimize the experiment. Here, we propose a method for fast and accurate defocus (FADE) modulation during movie acquisition. It uses the objective lens aperture as an electrostatic pole that locally modifies the electron beam potential. The beam potential variation is converted to defocus modulation by the typically undesired chromatic aberration of the objective lens. The simplicity, electrostatic principle and low electrical impedance of the device will allow fast switching speeds that will enable per-frame defocus values in cryo-EM movies. Researchers will be able to define custom defocus "recipes" and tailor the experiment for optimal information extraction from their sample. The FADE method could help to convert the microscope into a more dynamic and flexible optical platform that delivers better performance in cryo-EM single particle analysis and electron cryo-tomography.

biophysics↗

bioRxiv2017

Two-photon calcium imaging of medial prefrontal cortex and hippocampus without cortical invasion

In vivo two-photon calcium imaging currently allows us to observe the activity of multiple neurons up to [~]900 m below the cortical surface without cortical invasion. However, many other important brain areas are located deeper than this. Here, we used a 1100 nm laser, which underfilled the back aperture of the objective, and red genetically encoded calcium indicators to establish two-photon calcium imaging of the intact mouse brain and detect neural activity up to 1200 m from the cortical surface. This imaging was obtained from the medial prefrontal cortex (the prelimbic area) and the hippocampal CA1 region. We found that the neural activity related to reward prediction is higher in the prelimbic area than in layer 2/3 of the secondary motor area, while it is negligible in the hippocampal CA1 region. Reducing the invasiveness of imaging is an important strategy to reveal the brain processes active in cognition and memory.

neuroscience↗