Biology subjects

Tsurugizawa, T.

Publications and source records attributed to Tsurugizawa, T..

12 recordsLinked to original sources

bioRxiv2026

Dose-dependent effect of ketamine on functional connectivity in mice

A single injection of a subanesthetic dose of ketamine, an NMDA receptor antagonist, induces schizophrenia-like behavior in mice. Previous studies investigated the effect of single injection of ketamine on behavior and c-Fos expression in mice dose-dependently. However, there has not been functional magnetic resonance imaging (fMRI) study to investigate the effect of ketamine in mice. Here, we used awake fMRI and investigated the dose-dependent effect of single injection of ketamine in awaked mice. The lower-dose (5 mg/kg) ketamine increased functional connectivity (FC) with the thalamus and the hypothalamic nuclei. Higher-dose (50 mg/kg) ketamine increased widespread FC with cerebral cortex as well as hippocampus and thalamic nuclei. Graph theory analysis reveals that several regions of hypothalamus and cerebral cortex are essential for the network change by ketamine injection. These results indicate that sub-anesthetic ketamine dose-dependently alters the brain and indues the abnormal behavior in mice.

neuroscience↗

bioRxiv2026

Task-specific ISS reduction and network balance during Stroop task performance in older adults

Declines in the cognitive inhibition that comes with aging impacts daily life and independence. It is still debated whether overactivation during cognitive inhibition tasks in older adults is due to compensation or neural noise. To address this question, we examined age-related changes in inter-subject similarity (ISS) of functional connectivity from task-based and resting-state fMRI. Using Bayesian hierarchical modeling, we identified 27 Stroop task-related regions of interest and found that ISS in these regions was significantly reduced in older adults during task performance. Furthermore, aging is associated with a loss of consistent functional connectivity patterns in frontal regions, accompanied by the emergence of a convergent compensatory mechanism within visual attention regions. Principal component analysis of individual activation deviations from the group-mean pattern showed that task performance in older adults cannot be explained by overall task-related brain activation, but rather by a specific spatial component involving suppression of the default mode network and increased activity in visual attention regions. These findings indicate that task-related brain overactivation in older adults is not due to uniform noise or uniform compensation, but rather a spatially specific pattern of functional reorganization.

neuroscience↗

bioRxiv2026

Mosaic evolution of avian brain compartments revealed by comparative MRI

Birds evolved large, cognitively capable forebrains independently of mammals, yet comparative analyses of avian brain organization have been constrained by the lack of standardized resources capable of resolving internal parcellation and long-range connectivity across species. Here, we present a comparative MRI resource spanning 16 avian species representing major clades and diverse ecological niches. We analyzed high-resolution T2-weighted and diffusion-weighted datasets suitable for direct interspecific comparison. T2-weighted morphometry revealed pronounced region-specific variation in internal brain architecture, including lineage-dependent differences in the relative prominence of major brain divisions and commissural structures, supporting a pattern of mosaic diversification rather than uniform scaling. To validate MRI-derived anatomical boundaries, we compared MRI parcellations with complementary histological analyses in three representative taxa (the large-billed crow, gentoo penguin, and mandarin duck), demonstrating close correspondence between MRI-defined borders and cytoarchitectonic transitions identified by Nissl staining, as well as major myelinated compartments visualized by Luxol Fast Blue staining. Moreover, diffusion MRI tractography and fractional anisotropy (FA) mapping further revealed both conserved and species-specific features of large-scale brain organization. Seed-based tractography of the optic lobe, dorsal cortex, cerebellum, and anterior cortex in chick, gentoo penguin, and large-billed crow revealed conserved within-compartment trajectory patterns alongside marked region-specific interspecific differences, particularly in optic-lobe-associated long-range trajectories. Whole-brain FA maps revealed complementary variation in regional microstructural organization across taxa. Together, this comparative MRI framework provides a cross-validated foundation for linking internal brain anatomy and long-range connectivity to ecological and evolutionary diversification in birds, with broader applications to comparative neuroanatomy across amniotes. Significance StatementHow does the internal architecture of the brain reorganize as species adapt to diverse lifestyles? Traditional comparative neuroanatomy has largely relied on overall brain size and external morphology, providing limited insight into internal subdivisions and long-range connectivity. In this study, we present a standardized avian MRI resource and a reproducible analytical pipeline that enables direct cross-species comparisons of 3D morphometry and diffusion-derived connectivity across 16 bird species representing major clades and diverse ecological niches. MRI-derived anatomical boundaries are validated through complementary histological analyses, providing biological support for cross-species parcellation and white-matter measurements. Using this framework, we demonstrate that avian brains diversify in a strongly mosaic manner, with region-and pathway-specific changes that vary disproportionately across lineages rather than scaling uniformly with overall brain size. By moving beyond simple correlations between brain size and behavior, this resource provides a benchmark for testing hypotheses of mosaic brain evolution and for linking neural architecture to ecological and behavioral diversification across vertebrates.

zoology↗

bioRxiv2024

Zero-echo time imaging achieves whole brain activity mapping without ventral signal loss in mice

Functional MRI (fMRI) is an important tool for investigating functional networks. However, the widely used fMRI with T2*-weighted imaging in rodents has the problem of signal lack in the lateral ventral area of forebrain including the amygdala, which is essential for not only emotion but also noxious pain. Here, we scouted the zero-echo time (ZTE) sequence, which is robust to magnetic susceptibility and motion-derived artifacts, to image activation in the whole brain including the amygdala following the noxious stimulation to the hind paw. ZTE exhibited higher spatial and temporal signal-to-noise ratios than conventional fMRI sequences. Electrical sensory stimulation of the hind paw evoked ZTE signal increase in the primary somatosensory cortex. Formalin injection into the hind paw evoked early and latent change of ZTE signals throughout the whole brain including the subregions of amygdala. Furthermore, resting-state fMRI using ZTE demonstrated the functional connectivity, including that of the amygdala. These results indicate the feasibility of ZTE for whole brain fMRI, including the amygdala and we first show acute and latent activity in different subnuclei of the amygdala complex after nociceptive stimulation. Significance statementFunctional MRI (fMRI) is an important tool for investigating functional networks. However, the widely used fMRI in rodents has the problem of signal lack in the lateral ventral area of forebrain including the amygdala, which is essential for not only emotion but also noxious pain. Here, we used zero-echo time (ZTE) sequence, which was robust to susceptibility artifacts, for functional imaging in the whole brain including amygdala. We demonstrated the feasibility and advantages of using ZTE to investigate neuronal activity in mice. Furthermore, we first showed acute and latent activation in different subnuclei of the amygdala complex as well as other regions related to pain after nociceptive stimulation in mice.

neuroscience↗

bioRxiv2024

Age-related alterations in functional and structural networks in the brain in macaque monkeys

Resting-state networks (RSNs) have been used as biomarkers of brain diseases and cognitive performance. However, age-related changes in the RSNs of macaques, a representative animal model, are still not fully understood. In this study, we measured the RSNs in macaques aged 3-20 years and investigated the age-related changes from both functional and structural perspectives. The proportion of structural connectivity in the RSNs significantly decreased, whereas functional connectivity showed an increasing trend with age. Additionally, the amplitude of low-frequency fluctuations tended to increase with age, indicating that resting-state neural activity may be more active in the RSNs may increase with age. These results indicate that structural and functional alterations in typical RSNs are age-dependent and can be a marker of aging in the brain.

neuroscience↗

bioRxiv2023

A whole-brain analysis of functional connectivity and immediate early gene expression revealed functional network shifts after operant learning

Previous studies of operant learning have addressed neuronal activities and network changes in specific brain areas, such as the striatum, sensorimotor cortex, prefrontal/orbitofrontal cortices, and hippocampus. However, how changes in the whole-brain network are caused by cellular-level changes remains unclear. We combine resting-state functional magnetic resonance imaging (rsfMRI) and whole-brain immunohistochemical analysis of early growth response 1 (EGR1), a marker of neural plasticity, to elucidate the spatiotemporal functional network changes and underlying cellular processes during operant learning. We used an 11.7 Tesla scanner and whole-brain immunohistochemical analysis of EGR1 in mice during the early and late stages of operant learning. In the operant training, mice received a reward when they pressed the left and right buttons alternately and were punished with a bright light when they made a mistake. Control mice spent the same time and received the same amount of reward in the same operant box. A group of mice (n = 22) underwent the first rsfMRI before behavioral sessions, the second after 3 days of sessions (early stage), and the third after 21 days of sessions (late stage). Another group of mice (n = 40) was subjected to histological analysis 15 min after the early or late stages of behavioral sessions. After the early stage of training, functional connectivity was increased between the limbic areas and thalamus or auditory cortex, and the correlations of the number of EGR1-immunopositive cells between the limbic area and auditory cortex were also increased. After the late stage of training, the increases in functional connectivity and correlations of EGR1-immunopositive cells primarily occurred between the motor cortex, somatosensory cortex, and striatum. The subcortical networks centered around the limbic areas that emerged in the early stage have been implicated in rewards, pleasures, and fears. The connectivity between the motor cortex, somatosensory cortex, and striatum that consolidated in the late stage have been implicated in motor learning. Our multimodal longitudinal study successfully revealed the temporal shifts of brain regions involved in behavioral learning together with the underlying cellular-level plasticity between these regions for the first time. Our study represents a first step toward establishing a new experimental paradigm that combines rsfMRI and immunohistochemistry for linking macroscopic and microscopic mechanisms of learning.

neuroscience↗

bioRxiv2023

Astrocyte aquaporin mediates a tonic water efflux maintaining brain homeostasis

Brain water homeostasis not only provides a physical protection, but also determines the diffusion of chemical molecules key for information processing and metabolic stability. As a major type of glia in brain parenchyma, astrocytes are the dominant cell type expressing aquaporin water channel. How astrocyte aquaporin contributes to brain water homeostasis in basal physiology remains to be understood. We report that astrocyte aquaporin 4 (AQP4) mediates a tonic water efflux in basal conditions. Acute inhibition of astrocyte AQP4 leads to intracellular water accumulation as optically resolved by fluorescence-translated imaging in acute brain slices, and in vivo by fiber photometry in mobile mice. We then show that aquaporin-mediated constant water efflux maintains astrocyte volume and osmotic equilibrium, astrocyte and neuron Ca2+ signaling, and extracellular space remodeling during optogenetically induced cortical spreading depression. Using diffusion-weighted magnetic resonance imaging (DW-MRI), we observed that in vivo inhibition of AQP4 water efflux heterogeneously disturbs brain water homeostasis in a region-dependent manner. Our data suggest that astrocyte aquaporin, though bidirectional in nature, mediates a tonic water outflow to sustain cellular and environmental equilibrium in brain parenchyma. Significance statementOur brain is immersed, thus protected, in a water environment. It ensures intra- and extracellular molecular diffusion, which is vital for brain function and health. Brain water homeostasis is maintained by dynamic water transport between different cell types. Astrocytes are a main type of glial cell widely distributed in brain parenchyma, expressing the bidirectional aquaporin water channel. Here we show that in basal conditions, aquaporin channel mediates a tonic water efflux from astrocytes. This mechanism maintains astrocyte volume stability, activity-gated brain parenchyma remodeling and brain water homeostasis. Our finding sheds light on how astrocytes regulate water states in the brain, and will help to understand brain allostasis in specific life contexts.

physiology↗

bioRxiv2023

Increased interhemispheric functional connectivity during non-dominant hand movement in right-handed subjects

Hand preference is one of the behavioral expressions of lateralization in the brain. Previous fMRI studies, using conventional task-based functional MRI (fMRI), investigated the lateralization of brain function, and several regions including the motor cortex, putamen, thalamus, and cerebellum were activated during the single-hand movement. However, lateralization of functional connectivity related to hand preference has not been investigated. Here, we used the generalized psychophysiological interaction (gPPI) approach to investigate the alteration of functional connectivity during single-hand movement from the resting state in right-hand subjects. The functional connectivity in interhemispheric motor-related regions including the supplementary motor area, putamen, precentral gyrus, and cerebellum was significantly increased during non-dominant hand movement, while functional connectivity was not increased during dominant hand movement. The general linear model (GLM) showed activation in the left supplementary motor area, left precentral gyrus, and right cerebellum during right hand movement and activation in the right supplementary motor area, right precentral gyrus, and left cerebellum during left hand movement. These results indicate that a combination of GLM and gPPI analysis can detect the lateralization of hand preference more clearly in right-handed subjects.

neuroscience↗

bioRxiv2021

Impact of anaesthesia on static and dynamic functional connectivity in mice

A few studies have compared the static functional connectivity between awake and anaesthetized states in rodents by resting-state fMRI. However, impact of anaesthesia on static and dynamic fluctuations in functional connectivity has not been fully understood. Here, we developed a resting-state fMRI protocol to perform awake and anaesthetized functional MRI in the same mice. Static functional connectivity showed a widespread decrease under anaesthesia, such as when under isoflurane or a mixture of isoflurane and medetomidine. Several interhemispheric connections were key connections for anaesthetized condition from awake. Dynamic functional connectivity demonstrates the shift from frequent broad connections across the cortex, the hypothalamus, and the auditory-visual cortex to frequent local connections within the cortex only. Fractional amplitude of low frequency fluctuation in the thalamic nuclei decreased under both anaesthesia. These results indicate that typical anaesthetics for functional MRI alters the spatiotemporal profile of the dynamic brain network in subcortical regions, including the thalamic nuclei and limbic system. HighlightsO_LIResting-state fMRI was compared between awake and anaesthetized in the same mice. C_LIO_LIAnaesthesia induced a widespread decrease of static functional connectivity. C_LIO_LIAnaesthesia strengthened local connections within the cortex. C_LIO_LIfALFF in the thalamus was decreased by anaesthesia. C_LI

neuroscience↗

bioRxiv2020

Diffusion MRI reveals in vivo and non-invasively changes in astrocyte function induced by an aquaporin-4 inhibitor.

The Glymphatic System (GS) has been proposed as a mechanism to clear brain tissue from waste. Its dysfunction might lead to several brain pathologies, including the Alzheimers disease. A key component of the GS and brain tissue water circulation is the astrocyte which is regulated by acquaporin4 (AQP4), a membrane-bound water channel on the astrocytic end-feet. Here we investigated the potential of diffusion MRI to monitor astrocyte activity in a mouse brain model through the inhibition of AQP4 channels with TGN-020. Upon TGN-020 injection, we observed a significant decrease in the Sindex, a diffusion marker of tissue microstructure, and a significant increase of the water diffusion coefficient (sADC) in cerebral cortex and hippocampus compared to saline injection. These results indicate the suitability of diffusion MRI to monitor astrocytic activity in vivo and non-invasively.

neuroscience↗

bioRxiv2020

Differential effects of aquaporin-4 channel inhibition on BOLD fMRI and Diffusion fMRI responses in rat visual cortex

The contribution of astrocytes to the BOLD fMRI and DfMRI responses in visual cortex of mice following visual stimulation were investigated an aquaporin 4 (AQP4) channel blocker, TGN-020, acting as an astrocyte function perturbator. Under TGN-020 injection the amplitude of the BOLD fMRI response became significantly higher. In contrast no significant changes in the DfMRI responses and the electrophysiological responses were observed. Those results further confirm the implications of astrocytes in the neurovascular coupling mechanism underlying BOLD fMRI, while DfMRI relies on other, not astrocyte-mediated mechanisms.

neuroscience↗

bioRxiv2019

fMRI detects bilateral brain network activation following unilateral chemogenetic activation of direct striatal projection neurons

Although abnormal structural and functional connectivity in the striatum during neurological disorders has been reported using functional magnetic resonance imaging (fMRI), the effects of cell-type specific neuronal stimulation on fMRI and related behavioral alterations are not well understood. In this study, we successfully combined DREADD-technology with fMRI (chemo-fMRI) to investigate the alterations of spontaneous neuronal activity induced by the unilateral activation of dopamine D1 receptor-expressing neurons (D1-neurons) in the mouse dorsal striatum (DS). We compared the effects of two different DREADD ligands, clozapine (CLZ) and clozapine-N-oxide (CNO), on behavior and fMRI. We found that the effects of CLZ on behavior were more rapid than those of CNO. In fMRI, both systemic CLZ and CNO administrations, which evoked unilateral activations of D1-neurons in DS, increased the fractional amplitude of low frequency fluctuations (fALFF) in the thalamus and bilateral cortex. In addition, we found the increased gamma-band of local field potentials in DS and bilateral cortex after CLZ-evoked unilateral activation of D1-neuron in the striatum. These results provide bases for better interpretation of cell type-specific activity changes in fMRI.

neuroscience↗