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Hasegawa, I.

Publications and source records attributed to Hasegawa, I..

7 recordsLinked to original sources

Human parietal retrieval states prioritize an absent temporal reference to reconstruct event order

How the brain judges when something happened is thought to involve reconstruction--deriving temporal judgments from information recovered from memory rather than simply reading out a fixed temporal code. Testing this has been difficult because conventional tasks present both compared items at retrieval, so reinstatement could reflect cue processing as much as memory recovery. Here we dissociated what a judgment requires from what its cue supplies: during fMRI scanning, participants (n = 55) judged a targets temporal position relative to a milestone that was never shown at retrieval. We found that retrieval patterns in the precuneus and angular gyrus resembled the absent milestone more than the target, a bias strongest in the precuneus. Moreover, trial-by-trial similarity to the encoded path linking milestone to target--rather than to either alone--predicted correct judgments independently of retrieval activation. Human parietal retrieval is thus configured more by what a judgment requires than by what the cue supplies, providing content-specific representational evidence for reconstructive temporal-order memory.

neuroscience↗

Beyond Temporary Scaffolding: Persistent Hippocampal Engagement and Brain-Wide Network Reorganization in Remote Memory Consolidation

The standard model of memory consolidation posits a temporary role for the hippocampus. We challenge this view by combining a novel face-name associative memory task with cross-modal decoding of fMRI data. We demonstrate that the hippocampus remains persistently engaged in representing both recent and remote memories, with distinct subregional contributions: recent memories were represented in the right posterior hippocampus, whereas remote memories additionally recruited the left anterior hippocampus. This sustained hippocampal involvement occurred alongside a large-scale network reorganization. Remote memory retrieval was accompanied by increased global connectivity among semantic regions, yet the hippocampus itself did not emerge as a major hub. Instead, network hubs shifted from the medial prefrontal cortex (mPFC) for recent memories to the mPFC and bilateral inferior parietal lobule for remote memories. These findings reveal a dynamic process in which the hippocampus preserves long-lasting representational functions while the broader memory network undergoes extensive reorganization.

neuroscience↗

Hippocampal-midcingulate connectivity is associated with representational integration during cognitive map updating

Cognitive maps organize experience into structured internal models that support goal-directed behavior. Although map formation has been extensively studied in the human hippocampus, the neural mechanisms supporting flexible updating of established maps remain unclear. We used fMRI to track the formation and updating of a spatial cognitive map across three days. Participants learned object-location associations and later updated them by remapping objects among fixed locations. Representational similarity analysis revealed two concurrent signatures in the right hippocampus: prior relational structure remained differentiated, whereas updated associations became integrated. Map updating engaged a frontoparietal network and modulated hippocampal-cortical connectivity. Critically, hippocampal-midcingulate connectivity was associated with the integration of updated associations, but not with the differentiation of prior relational structure. These results suggest that cognitive map updating involves coordinated hippocampal-cortical interactions that incorporate new information while preserving prior relational structure, reflecting a balance of stability and plasticity in internal models.

neuroscience↗

MEIS1 is Required for Establishing Bergmann Glia-Specific Properties in the Developing Cerebellum

Compared to normal multipolar astrocytes, Bergmann glial cells (BGs), specifically differentiated astrocytes in the cerebellum, possess unique unipolar morphology and additional cellular functions. However, the molecular mechanisms that confer BG-specific properties onto normal multipolar astrocytes remain unknown. Here, we show that the transcription factor, MEIS1, is involved in BGs acquiring their unique characteristics. Targeted disruption of Meis1 in the whole cerebellum or astroglial lineage cells resulted in a marked reduction of BGs accompanied by an increase in multipolar astrocytes in mice. Postnatal deletion of Meis1 in Bergmann glia-like progenitors (BGLPs), which produce both BGs and multipolar astrocytes, suppressed their differentiation into BGs while promoting into multipolar astrocytes. Single-cell RNA sequencing, immunohistochemistry, and ChIP-Atlas analyses indicated that MEIS1 directly upregulates expression of BG-specific genes, including Vimentin and Zeb2, which are known to contribute to the correct localization and the unipolar process formation of BGs. These findings suggest that MEIS1 promotes the endowment of BG-specific properties to astrocytes by controlling the expression of BG-specific genes, thereby ensuring proper differentiation of BGLPs into BGs.

developmental biology↗

Lineage Analysis and Molecular Characterization of Bergmann Glia-like Progenitors in the Postnatal Mouse Cerebellum using in vivo Electroporation and Spatial Transcriptomics

In the mammalian cerebellum, three types of astroglial cells--Bergmann glial cells (BGs), inner granule cell layer (IGL) astrocytes, and white matter (WM) astrocytes--arise in postnatal timing from two types of progenitors: Bergmann glia-like progenitors (BGLPs) and astrocyte-like progenitors (AsLPs). In contrast to AsLPs, which are commonly observed in other brain regions, BGLPs have not been well studied. Here we investigate their dynamic changes in number, their differentiation abilities and their gene expression profiles during cerebellar development. BGLPs and AsLPs decrease in number as development progresses from P0, and are almost absent by P10. We developed an electroporation-based method to investigate the progeny cells of BGLPs. We found that BGLPs at P6 differentiate into BGs and IGL astrocytes, but not into WM astrocytes, which is consistent with a previous report. However, BGLPs at P0 were observed to differentiate into not only BGs and IGL astrocytes, but also WM astrocytes, indicating that P0 BGLPs possess wider pluripotency than P6 BGLPs. By conducting spatial transcriptomic analysis of the cerebellum at P0 and P6 with over 5,000 probes (Xenium, 5k), we successfully obtained clusters corresponding to BGLPs at P0 and P6, respectively. Further informatics analyses suggested that P0 BGLPs exhibit more stem cell-like features, while P6 BGLPs show a shift toward BG-like characteristics. This study, which includes transcriptome big data, will contribute to understanding the differentiation of BGs and astrocytes, as well as other types of cells, during postnatal cerebellar development.

developmental biology↗

AUTS2, a causative gene for microcephaly, regulates division of intermediate progenitor cells and production of upper-layer neurons

AUTS2 mutations often exhibit neurodevelopmental disorders and microcephaly. However, how AUTS2 regulates neuron production and affects brain size remains unclear. Here, we show that AUTS2 cooperates with the Polycomb complex PRC2 to regulate gene expression and cortical neurogenesis. Auts2 mutant mice exhibit reduced division of intermediate progenitor cells (IPCs), leading to decreased neurons and thickness in the upper-layer cortex. Expression of Robo1 is increased in the mutants, which in turn suppresses IPC division. Transcriptome and chromatin profiling experiments show that, in IPCs, AUTS2 primarily represses transcription of genes, including Robo1. Promoter region of AUTS2 target genes is enriched with H3K27me3, a repressive histone modification, but its levels are reduced in Auts2 mutants. AUTS2 interacts with PRC2, and together, they promote IPC division. These suggest that AUTS2 collaborates with PRC2 to repress gene transcription through H3K27 trimethylation, promoting neuron production. This sheds light on AUTS2 pathophysiological mechanisms in neurogenesis and microcephaly.

neuroscience↗

Neural oscillatory activities in separate frequencies encode hierarchically distinct visual features

Although most previous studies in cognitive neuroscience have focused on the change of the neuronal firing rate under various conditions, there has been increasing evidence that indicates the importance of neuronal oscillatory activities in cognition. In the visual cortex, specific time-frequency bands are thought to have selectivity to visual stimuli. Furthermore, several recent studies have shown that several time-frequency bands are related to frequency-specific feedforward or feedback processing in inter-areal communication. However, few studies have investigated detailed visual selectivity of each time-frequency band, especially in the primate inferior temporal cortex (ITC). In this work, we analyze frequency-specific electrocorticography (ECoG) activities in the primate ITC by training encoding models that predict frequency-specific amplitude from hierarchical visual features extracted from a deep convolutional neural network (CNNs). We find that ECoG activities in two specific time-frequency bands, theta (around 5 Hz) and gamma (around 20-25 Hz) bands, are better predicted from CNN features than the other bands. Furthermore, theta- and gamma-band activities are better predicted from higher and lower layers in CNNs, respectively. Our visualization analysis using CNN-based encoding models qualitatively show that theta- and gamma-band encoding models have selectivity to higher- and lower-level visual features, respectively. Our results suggest that neuronal oscillatory activities in theta and gamma bands carry distinct information in the hierarchy of visual features, and that distinct levels of visual information are multiplexed in frequency-specific brain signals.

neuroscience↗