Biology subjects

Shibata, K.

Publications and source records attributed to Shibata, K..

17 recordsLinked to original sources

bioRxiv2026

Perceptual similarity representations beyond the sensory cortex

It is commonly thought that information supporting conscious perception is primarily represented in sensory cortices, whereas association cortex encodes more abstract, task-dependent information. However, this impression may partly stem from difficulties in experimentally assessing the functions of association areas characterized by mixed selectivity and complex spatial topography. Here, we combined repetition-suppression (RS) and multi-voxel pattern analysis (MVPA) to extract richer information from human fMRI. With this approach, we asked whether association regions represent the perceptual similarity structure among color stimuli, although this perceptual similarity information was task-irrelevant in the experiment. Our analysis revealed such representations beyond the visual cortex, in lateral prefrontal, and parietal regions. We further demonstrated an electrophysiological complement to the fMRI findings by applying the same approach to local field potentials recorded in the macaque dorsomedial parietal cortex. Our findings suggest that higher-order areas beyond the visual cortex may play a key role in subjective color perception.

neuroscience↗

bioRxiv2026

Molecular factors shaping small RNA content in mouse sperm

In mammalian reproduction, sperm and oocytes fuse to generate embryos. In contrast to maternally inherited small RNAs, sperm-borne small RNAs have been implicated in embryo viability but remain incompletely understood. Unanswered questions about molecular forces shaping small RNA content in sperm and sources of reporting discrepancies hinder a deeper understanding of their post-fertilization roles. Here, we investigate the dynamics and protein association of small RNAs in C57BL/6 mice during spermiogenesis and sperm capacitation. Using unique molecular identifiers and spike-ins to minimize technical biases in low-input sequencing, we demonstrate a selective sperm small RNA repertoire derived from a subset of spermatogenic small RNAs that remains malleable during capacitation. Retained PIWI-interacting RNAs persist despite widespread RNA decay and are insensitive to capacitation, which may be partly attributed to their association with MIWI proteins. Our data reveal RNA species susceptible to PCR duplicate-related abundance overestimation and uncover biological and technical factors shaping experimentally observed sperm small RNA profiles. These findings refine our understanding of sperm-borne RNAs and inform future functional studies and medically assisted reproduction.

molecular biology↗

bioRxiv2026

Somatosensory information drives modification of a motor memory

The role of somatosensory information in motor memory modification remains controversial. One view holds that somatosensory information plays only a supportive role, such as feedback or sensory calibration, and is not directly involved in memory modification itself. An alternative view is that afferent somatosensory information, on its own, can modify motor memory. Here we resolve this controversy by isolating somatosensory information from voluntary motor execution using a hand-exoskeleton robot. Participants first learned a sequential finger movement task through voluntary practice. Their learned finger movements were recorded using a data glove. On subsequent days, they underwent a brief, 30-sec reinstatement session: either exoskeleton-based reinstatement, which reproduced their learned movements without voluntary execution, or voluntary reinstatement, in which they executed the trained task. Exoskeleton-based reinstatement led to subsequent performance gains comparable to those induced by voluntary reinstatement. This gain was not explained by replay of visual information, mental rehearsal, enhanced arousal, or warm-up effects induced by exoskeleton-driven movements. Rather, the results indicate that brief reinstatement of somatosensory information alone is sufficient to drive performance gain. We further found that exoskeleton-based exposure to a sequence that only partially matched the trained sequence yielded performance gains, whereas voluntary execution of the same partially matched sequence did not. This dissociation suggests that somatosensory information broadly activates a relevant motor skill memory, whereas voluntary execution activates memory in a sequence-specific manner. Together, these findings resolve a long-standing controversy in motor learning research by showing that afferent somatosensory information alone enables sequential motor memory modification through a route distinct from voluntary execution.

neuroscience↗

bioRxiv2026

Multitasking boosts muscular endurance task performance due to elevated arousal level unattainable by the endurance task alone

Multitasking is generally regarded as detrimental to performance. This deterioration effect is typically explained by the interference among tasks due to the limited capacity of information-processing resources, which in turn reduces the performance in each task. Contrary to this general view, we report evidence for a facilitation effect of multitasking on performance. This facilitation effect was observed in multitasking on a handgrip muscular endurance task and cognitive task, which are known to have little interference with each other. Specifically, we found that performance in the endurance task was facilitated with the difficulty of the concurrent cognitive task. This facilitation effect was mediated by additional pupil dilation due to the cognitive task. Increased effort with the difficulty of the cognitive task cannot explain the facilitated performance in the irrelevant endurance task. Instead, they suggest that the cognitive task elevated overall arousal to a level unattainable by the endurance task alone, which in turn facilitated performance in the irrelevant endurance task. To further test this arousal account, we manipulated participants motivation to the cognitive task by reward without changing its difficulty and found the same pattern of results. Thus, it is not effort or motivation specific to the cognitive task but rather overall arousal level that underlies the facilitation effect. These results unveiled a previously overlooked mechanism: a multitasking-induced arousal boost. Our findings suggest that multitasking can facilitate performance when the net effect of adding a concurrent task is governed less by the capacity limitation and more by the elevation of overall arousal.

neuroscience↗

bioRxiv2025

pH-Sensitive Amino Lipid-Driven Pore Formation Enables Endosomal Escape of Lipid Nanoparticles

Lipid nanoparticles (LNPs) have transformed nucleic acid delivery for vaccines and gene therapies, yet their efficiency remains limited by incomplete endosomal escape. While experimental studies have revealed endosomal membrane disruption facilitating cytosolic release, the molecular basis of this process remains poorly understood. Here, we employ molecular simulations to elucidate how LNPs fuse with the endosomal membrane and release their payloads. We identify multiple fusion pathways, with a dominant stalk-pore mechanism. Our simulations reproduce and rationalize key experimental observations, including the transfer of ionizable lipids from LNPs to the membrane, which promotes nucleic acid reorientation and facilitates stalk formation and expansion. Furthermore, lipid shape, pH sensitivity, membrane tension, and nucleic acid encapsulation emerge as critical molecular determinants of endosomal escape efficiency. These findings advance our mechanistic understanding of intracellular delivery and provide a framework for the rational design of LNPs with improved performance for gene therapies and RNA vaccines.

biophysics↗

bioRxiv2025

Cryo-EM Structures of Methanogenic Schizorhodopsins Reveal Divergent Strategies for Proton Transport and Thermal Adaptation

Schizorhodopsins (SzRs) are light-driven inward proton pumps found in Asgard archaea, contrasting with most microbial rhodopsins that export protons. Some SzRs, including Methanoculleus taiwanensis SzR (MtSzR) and Methanoculleus sp. SzR (MsSzR), exhibit remarkable heat tolerance, suggesting structural adaptations to extreme environments. Here, we report cryo-electron microscopy structures of MtSzR and MsSzR at 2.4 and 2.7 [A] resolutions, respectively, revealing distinct mechanisms for proton transport and thermostability. Both proteins share a cytoplasm-facing proton acceptor, yet MtSzR employs a hydrophobic gating mechanism, whereas MsSzR lacks this barrier and stabilizes its acceptor through a salt-bridge network. Thermostability also diverges: MtSzR relies on proline-rich loops and electrostatic interactions, while MsSzR achieves stability through reinforced trimerization and extensive interhelical aromatic packing. Structural and mutational analyses highlight the adaptability of SzRs and provide a framework for engineering robust photoreceptors for optogenetics and synthetic biology.

biophysics↗

bioRxiv2025

Glial Contribution to the Pathogenesis of Post-Operative Delirium Revealed by Multi-omic Analysis of Brain Tissue from Neurosurgery Patients

Post-operative delirium (POD) is a common complication after surgery especially in elderly patients, characterized by acute disturbances in consciousness and cognition, which negatively impacts long-term outcomes. Effective treatments remain elusive due to the unclear pathophysiology of POD. To address the knowledge gap, we investigated DNA methylation profiles and gene expression changes in brain cells from POD and non-POD patients who underwent brain resection surgery for medication refractory epilepsy. DNA methylation analysis revealed alteration in epigenetic status of immune and inflammation-related genes. Single-nucleus RNA sequencing (snRNAseq) identified POD-specific glial cell alterations, particularly in microglia, where neuroinflammation was strongly enhanced, consistent with epigenetic findings. Astrocytes exhibited changes in synapse-related functions and migration. Furthermore, downstream analysis indicated similarities between POD-associated glial cell states and pathologies such as encephalitis and dementia. Overall, this study--the first multi-omics analysis of brain tissue from POD patients--provides direct evidence of glial cell contributions to POD pathogenesis, and highlights potential therapeutic targets.

neuroscience↗

bioRxiv2024

Practice Reshapes the Geometry and Dynamics of Task-tailored Representations

Extensive practice makes task performance more efficient and precise, leading to automaticity. However, theories of automaticity differ on which levels of task representations (e.g., low-level features, stimulus-response mappings, or high-level conjunctive memories of individual events) change with practice, despite predicting the same pattern of improvement (e.g., power law of practice). To resolve this controversy, we built on recent theoretical advances in understanding computations through neural population dynamics. Specifically, we hypothesized that practice optimizes the neural representational geometry of task representations to minimally separate the highest-level task contingencies needed for successful performance. This involves efficiently reaching conjunctive neural states that integrate task-critical features nonlinearly while abstracting over non-critical dimensions. To test this hypothesis, human participants (n = 40) engaged in extensive practice of a simple, context-dependent action selection task over 3 days while recording EEG. During initial rapid improvement in task performance, representations of the highest-level, context-specific conjunctions of task-features were enhanced as a function of the number of successful episodes. Crucially, only enhancement of these conjunctive representations, and not lower-order representations, predicted the power-law improvement in performance. Simultaneously, over sessions, these conjunctive neural states became more stable earlier in time and more aligned, abstracting over redundant task features, which correlated with offline performance gain in reducing switch costs. Thus, practice optimizes the dynamic representational geometry as task-tailored neural states that minimally tesselate the task space, taming their high-dimensionality.

neuroscience↗

bioRxiv2024

Unsupervised learning as a computational principle works in visual learning of natural scenes, but not of artificial stimuli

Unsupervised learning--learning through repeated exposure without instruction or reward--is central to both machine learning and human cognition, including language acquisition and statistical learning. However, its role in visual perceptual learning (VPL) remains debated, as previous studies have not shown VPL for task-irrelevant but visible features, particularly in artificial stimuli. Here, we show that task-irrelevant exposure to natural scene images induces robust VPL, while artificial images that lack complex structure characteristics of natural scene images, known as higher-order statistics, do not. Behavioral and fMRI results suggest that although unsupervised learning underlies VPL, it can be suppressed by top-down attention. Higher-order statistics may evade this suppression, possibly because their slower processing reaches visual areas beyond V1 outside the optimal temporal window for attentional suppression. These findings suggest that unsupervised learning underlies VPL, but its occurrence depends on both higher-order stimulus structure and the brains attentional gating mechanisms.

neuroscience↗

bioRxiv2024

Working memory as a representational template for reinforcement learning

Working memory (WM) and reinforcement learning (RL) both influence decision-making, but how they interact to affect behaviour remains unclear. We assessed whether RL is influenced by the format of visual stimuli in WM, either feature-based or unified, object-based representations. In a pre-registered paradigm, participants learned stimulus-action combinations, mapping four stimuli onto two feature dimensions to one of two actions through probabilistic feedback. In parallel, participants retained the RL stimulus in WM and were asked to recall this stimulus after each trial. Crucially, the format of representation probed in WM was manipulated, with blocks encouraging either separate features or bound objects to be remembered. Incentivising a feature-based WM representation facilitated feature-based learning, shown by an improved choice strategy. This reveals a role of WM in providing sustained internal representations that are harnessed by RL, providing a framework by which these two cognitive processes cooperate.

neuroscience↗

bioRxiv2024

The bispectral EEG (BSEEG) method quantifies post-operative delirium-like states in young and aged mice after head mount implantation surgery

Delirium, a syndrome characterized by an acute change in attention, awareness, and cognition, is commonly observed in older adults and has multiple potential triggers, including illness, drug, trauma, and surgery. There are few quantitative monitoring methods in clinical settings. We developed the bispectral electroencephalography (BSEEG) method in clinical research that can detect the presence of and quantify the severity of delirium using a novel algorithm. In the pre-clinical model, we reported that the BSEEG method can capture a delirium-like state in mice following LPS administration. However, its application to post-operative delirium (POD) has not yet been validated in animal experiments. Therefore, this study aimed to create a POD model mouse with the BSEEG method by monitoring BSEEG scores after EEG head-mount implantation surgery throughout the recovery phase. We compared the BSEEG scores of C57BL/6J young (2-3 months old) with aged (18-19 months old) mice for quantitative evaluation of the delirium-like state after the surgery. Postoperatively, both groups showed increased BSEEG scores and a loss of regular diurnal changes in BSEEG scores every daytime and night. In young mice, BSEEG scores and regular diurnal changes recovered relatively quickly to baseline by around postoperative day 3. On the other hand, aged mice had prolonged increases in postoperative BSEEG scores and it reached steady state only after around postoperative day 8. This study suggests the BSEEG method can be utilized to quantitatively evaluate POD and also assess the effect of aging on recovery from POD in pre-clinical model.

neuroscience↗

bioRxiv2023

A Transient High-dimensional Geometry Affords Stable Conjunctive Subspaces for Efficient Action Selection

Flexible action selection requires cognitive control mechanisms capable of mapping the same inputs to different output actions depending on the context. From a neural state-space perspective, this requires a control representation that separates similar input neural states by context. Additionally, for action selection to be robust and time-invariant, information must be stable in time, enabling efficient readout. Here, using EEG decoding methods, we investigate how the geometry and dynamics of control representations constrain flexible action selection in the human brain. Participants performed a context-dependent action selection task. A forced response procedure probed action selection different states in neural trajectories. The result shows that before successful responses, there is a transient expansion of representational dimensionality that separated conjunctive subspaces. Further, the dynamics stabilizes in the same time window, with entry into this stable, high-dimensional state predictive of individual trial performance. These results establish the neural geometry and dynamics the human brain needs for flexible control over behavior.

neuroscience↗

bioRxiv2021

Functional roles of multiple Ton complex genes in a Sphingobium degrader of lignin-derived aromatic compounds

TonB-dependent transporters (TBDTs) mediate outer membrane transport of nutrients using the energy derived from proton motive force transmitted from the TonB-ExbB-ExbD complex localized in the inner membrane. Recently, we discovered ddvT encoding a TBDT responsible for the uptake of a 5,5-type lignin-derived dimer in Sphingobium sp. strain SYK-6. Furthermore, overexpression of ddvT in an SYK-6-derivative strain enhanced its uptake capacity, improving the rate of platform chemical production. Thus, understanding the uptake system of lignin-derived aromatics is fundamental for microbial conversion-based lignin valorization. Here we examined whether multiple tonB-, exbB-, and exbD-like genes in SYK-6 contribute to the outer membrane transport of lignin-derived aromatics. The disruption of tonB2-6 and exbB3 did not reduce the capacity of SYK-6 to convert or grow on lignin-derived aromatics. In contrast, the introduction of the tonB1-exbB1-exbD1-exbD2 operon genes into SYK-6, which could not be disrupted, promoted the conversion of {beta}-O-4-, {beta}-5-, {beta}-1-, {beta}-{beta}-, and 5,5-type dimers and monomers, such as ferulate, vanillate, syringate, and protocatechuate. These results suggest that TonB-dependent uptake involving the tonB1 operon genes is responsible for the outer membrane transport of the above aromatics. Additionally, exbB2/tolQ and exbD3/tolR were suggested to constitute the Tol-Pal system that maintains the outer membrane integrity.

microbiology↗

bioRxiv2020

Visual perceptual learning of a primitive feature in human V1/V2 as a result of unconscious processing, revealed by Decoded fMRI Neurofeedback (DecNef)

While numerous studies have shown that visual perceptual learning (VPL) occurs as a result of exposure to a visual feature in a task-irrelevant manner, the underlying neural mechanism is poorly understood. In a previous psychophysical study, subjects were repeatedly exposed to a task-irrelevant global motion display that induced the perception of not only the local motions but also a global motion moving in the direction of the spatiotemporal average of the local motion vectors. As a result, subjects enhanced their sensitivity only to the local moving directions, suggesting that early visual areas (V1/V2) that process local motions are involved in task-irrelevant VPL. However, this hypothesis has never been examined by directly examining the involvement of early visual areas (V1/V2). Here, we employed a decoded neurofeedback technique (DecNef) using functional magnetic resonance imaging. During the DecNef training, subjects were trained to induce the activity patterns in V1/V2 that were similar to those evoked by the actual presentation of the global motion display. The DecNef training was conducted with neither the actual presentation of the display nor the subjects awareness of the purpose of the experiment. As a result, subjects increased the sensitivity to the local motion directions but not specifically to the global motion direction. The training effect was strictly confined to V1/V2. Moreover, subjects reported that they neither perceived nor imagined any motion during the DecNef training. These results together suggest that that V1/V2 are sufficient for exposure-based task-irrelevant VPL to occur unconsciously. Significance StatementWhile numerous studies have shown that visual perceptual learning (VPL) occurs as a result of exposure to a visual feature in a task-irrelevant manner, the underlying neural mechanism is poorly understood. Previous psychophysical experiments suggest that early visual areas (V1/V2) are involved in task-irrelevant VPL. However, this hypothesis has never been examined by directly examining the involvement of early visual areas (V1/V2). Here, using decoded fMRI neurofeedback, the activity patterns similar to those evoked by the presentation of a complex motion display were repeatedly induced only in early visual areas. The training sensitized only the local motion directions and not the global motion direction, suggesting that V1/V2 are involved in task-irrelevant VPL.

neuroscience↗

bioRxiv2020

MRS-measured Glutamate versus GABA reflects excitatory versus inhibitory neural activities in awake mice

To assess if magnetic resonance spectroscopy (MRS)-measured Glutamate (Glu) and GABA reflect excitatory and inhibitory neural activities, respectively, we conducted MRS measurements along with two-photon mesoscopic imaging of calcium signals in excitatory and inhibitory neurons of living, unanesthetized mice. For monitoring stimulus-driven activations of a brain region, MRS signals and mesoscopic neural activities were measured during two consecutive sessions of 15-min prolonged sensory stimulations. In the first session, putative excitatory neuronal activities were increased, while inhibitory neuronal activities remained at the baseline level. In the second half, while excitatory neuronal activities remained elevated, inhibitory neuronal activities were significantly enhanced. We also assessed regional neurochemical and functional statuses related to spontaneous neural firing by measuring MRS signals and neuronal activities in a mouse model of Dravet syndrome under a resting condition. Mesoscopic assessments showed that activities of inhibitory neurons in the cortex were diminished relative to wild-type mice in contrast to spared activities of excitatory neurons. Consistent with these observations, the Dravet model exhibited lower concentrations of GABA than wild-type controls. Collectively, the current investigations demonstrate that the MRS-measured Glu and GABA can reflect spontaneous and stimulated activities of neurons producing and releasing these neurotransmitters in an awake condition.

neuroscience↗

bioRxiv2018

Domain organization and conformational change of dynactin p150

Dynactin is a principal regulator of the minus-end directed microtubule motor dynein. The sidearm of dynactin is essential for binding to microtubules and regulation of dynein activity. Although our understanding of the structure of the dynactin backbone (Arp1 rod) has greatly improved recently, structural details of the sidearm part remain elusive. Here, electron microscopy of individual molecules of the dynactin complex revealed that the sidearm was highly flexible and exhibited diverse morphologies. Utilizing mutants for nanogold labeling and deletion analysis, we determined the domain organization of the largest subunit p150 and identified a filamentous structure protruding from the head domain of the sidearm as the coiled-coil 1 (CC1), the dynein-binding domain, in p150. Furthermore, the protrusion formed by CC1 exhibited either a folded or an extended form, suggesting that CC1 works as an extending \"arm\". These findings provide clues to understand how dynactin binds to microtubules and regulates dynein.

biophysics↗

bioRxiv2018

Endogenous controllability of closed-loop brain-machine interfaces for pain.

The ultimate aim of closed-loop brain-machine systems for pain is to directly titrate the ongoing level of an intervention to pain-related neural activity. However pain is highly susceptible to endogenous modulation, raising the possibility that active or passive changes in neural activity provoked by the operation of the system could enhance or interfere with the signals upon which it is based. We studied healthy subjects receiving intermittent pain stimuli in a real-time fMRI-based closed-loop feedback-stimulation task. We showed that multi-voxel pattern decoding of pain intensity could be used to train a control algorithm to learn to deliver less painful stimuli (adaptive decoded neurofeedback). However, the system engaged two types of endogenous processes in the brain. First, despite the inherent incentive for subjects to enhance the neural decodability of pain, decodability was either reduced or unchanged in classic pain-processing regions, including insula, dorsolateral prefrontal, and somatosensory cortices. However, increased decodability was observed in a putative pain modulatory region - the pregenual anterior cingulate cortex (pgACC). Second, we found that pain perception itself was modulated by an endogenous computational uncertainty signal engaged as subjects learned the success rate of the system in reducing pain - an effect that also correlated with pgACC responses. The results illustrate how regionally and computationally specific co-adaptive brain-machine learning influences the efficacy of closed-loop systems for pain, and shows that pgACC acts as a key hub in the endogenous controllability of pain.

neuroscience↗