Biology subjects

Shinohara, Y.

Publications and source records attributed to Shinohara, Y..

7 recordsLinked to original sources

bioRxiv2026

Multi-omics analysis reveals chromatin and transcriptomic remodeling in hippocampal CA1 following adolescent social isolation

Social isolation (SI) during adolescence is associated with neurobiological alterations; however, its effect on the hippocampal epigenome and transcriptome remains unclear. We performed ATAC-seq and RNA-seq of hippocampal CA1 in an adolescent mouse SI model, with single-cell RNA-seq reference mapping and cell type deconvolution. ATAC-seq identified candidate SI-associated chromatin accessibility alterations, with nominal functional enrichment linking increased enhancer-associated regions to calcium transport and decreased promoter regions to synaptic organization. Motif analysis showed enrichment of the activator protein 1 (AP-1) motif among candidate regions with reduced accessibility. RNA-seq identified 106 differentially expressed genes (DEGs), including upregulated Fosl2 and Hdac9 and downregulated Fbxw7, with enrichment of myelination-related pathways. Although global concordance between chromatin accessibility and transcriptional changes was limited, integrated analysis showed directional concordance between expression and nearby candidate accessibility changes for a subset of DEGs. Cell type analyses suggested that SI-downregulated transcriptional signatures were linked to excitatory neurons, whereas SI-upregulated signatures were enriched in non-neuronal populations, particularly oligodendrocytes. Deconvolution suggested higher estimated oligodendrocyte representation and lower estimated excitatory neuron representation in isolated mice. These findings suggest that adolescent SI is associated with significant transcriptomic remodeling and candidate chromatin accessibility changes within hippocampal CA1, accompanied by distinct neuronal- and glial-associated transcriptional signatures.

neuroscience↗

bioRxiv2026

Left-right asymmetry of the microminipig brain.

Left-right asymmetry of the brain is well recognized in various animals including C. elegans, drosophila and zebrafish. In primates, most of the brain studies describe side of the brain. However, in spite of huge amounts of accumulating rodent studies on neuroscience, most of rodent studies do not distinguish the brain side. The pig brain is considered to occupy an intermediate position between primates and rodents in terms of structural complexity and brain function. Moreover, the numbers of studies using genetic manipulation of pigs are drastically increasing. So, we investigated microminipig (MMP) brain mesoscopic anatomy focusing on left-right differences of its morphology. Here, we show the anterior cingulate cortex, perirhinal cortex, and cerebellum of male and female MMPs, are structurally asymmetrical. The cerebellar vermis, paravermis is tilted from the midline and the consequently the cerebellar cortex exhibits asymmetrical morphology. The anterior cingulate gurus exhibited protrusion and invagination toward the midline on the right and left side, respectively. The left perirhinal lobe exhibited distinct patterns of cortical gyration between left and right side. These data demonstrate that MMPs are one of the suitable model animals for investigating cerebral and cerebellar asymmetry.

neuroscience↗

bioRxiv2025

Housing environment bilaterally alters transcriptomic profile in the rat hippocampal CA1 region

Brain asymmetry is a fundamental feature of neural organization. However, the molecular basis of hippocampal lateralization in response to environmental stimuli remains poorly understood. Here, we examined the transcriptomic profiles of the left and right hippocampal CA1 regions in rats reared under isolated or enriched housing conditions to elucidate hemisphere-specific responses and shared molecular adaptations. RNA-sequencing analysis revealed lateralized differences in the number and identity of differentially expressed genes, accompanied by distinct biological themes, as indicated by overrepresentation and gene set enrichment analysis. The left CA1 region was prominently engaged in pathways related to synaptic organization and mitochondrial function, whereas the right CA1 region exhibited enrichment in transcriptional regulation and RNA metabolic processes. Despite these asymmetries, co-expression and protein-protein interaction network analyses revealed shared molecular architectures. Immediate early genes formed consistent central hubs across both hemispheres, and a common Mecp2-Grin2b-Cdkl5-Tet3 protein interaction cluster was identified as a potential integrative regulatory module. Additional enrichment analysis of differentially expressed genes shared between hemispheres further highlighted conserved responses, particularly in synaptic plasticity and cell-cell communication. Together, these findings demonstrate that the left and right CA1 regions employ distinct yet partially convergent transcriptional programs to adapt to environmental stimuli. This coordinated molecular asymmetry provides novel insights into hippocampal lateralization and its role in experience-dependent brain plasticity.

neuroscience↗

bioRxiv2023

Axonal selectivity of myelination by single oligodendrocytes established during development in mouse cerebellar white matter

Myelin formation by oligodendrocytes regulates conduction velocity and functional integrity of neuronal axons. While individual oligodendrocytes form myelin sheaths around multiple axons and control the functions of neural circuits in the brains, it remains unclear if oligodendrocytes selectively form myelin sheaths around the specific types of axons. In this study, we developed a method for observing a single oligodendrocyte and its myelin sheaths around different types of axons in the mouse cerebellar white matter. This was achieved by combining sparse fluorescent labeling of oligodendrocytes by attenuated rabies virus and subsequent immunostaining for axonal markers along with tissue clearing. We revealed that approximately half of the oligodendrocytes showed a preferential myelination of axons originating from Purkinje cells in the adult mice. The preference for Purkinje cell axons was more pronounced during development, when the process of myelination within cerebellar white matter was initiated; over 90% of oligodendrocytes preferentially myelinated the Purkinje cell axons. The transgenic mice that label early born oligodendrocytes showed that their myelin sheaths were predominantly formed around Purkinje cell axons in the adult cerebellar white matter. These results suggest that a significant proportion of oligodendrocytes preferentially myelinate functionally distinct axons in the cerebellar white matter, and the axonal preference of myelination is established during development.

neuroscience↗

bioRxiv2023

Cortical parvalbumin neurons are responsible for homeostatic sleep rebound through CaMKII activation

The homeostatic regulation of sleep is characterized by rebound sleep after prolonged wakefulness, but the molecular and cellular mechanisms underlying this regulation are still unknown. We show here that CaMKII-dependent activity control of parvalbumin (PV)-expressing cortical neurons is involved in sleep homeostasis regulation. Prolonged wakefulness enhances cortical PV-neuron activity. Chemogenetic suppression or activation of cortical PV neurons inhibits or induces rebound sleep, implying that rebound sleep is dependent on increased activity of cortical PV neurons. Furthermore, we discovered that CaMKII kinase activity boosts the activity of cortical PV neurons, and that kinase activity is important for homeostatic sleep rebound. We propose that CaMKII-dependent PV-neuron activity represents negative feedback inhibition of cortical neural excitability, which serves as the distributive cortical circuits for sleep homeostatic regulation.

neuroscience↗

bioRxiv2023

The defects of the hippocampal ripples and theta rhythm in depression, and the effects of physical exercise on their amelioration.

Accumulated evidence demonstrate that environmental stress affects the hippocampus, functioning in cognition and sociality, and causes various depressive symptoms. In addition, recent findings showed that environmental stress influenced the hippocampal activity correlated with neuroinflammation, and impaired the hippocampal sharp wave ripples (SWRs), pattens of spike sequences, and the theta rhythms, a strong oscillation observed in the hippocampus. The involvement of the electrophysiological alterations in the etiology of depression has not been appreciated especially in the hippocampus. Furthermore, the pathological markers associated with such alterations have not been identified. In the present study, therefore, the impairment of the SWRs and the theta rhythms in the hippocampus of the restraint stress-induced depression model of mice was analyzed. In the model mice the hippocampal SWRs and theta rhythms were impaired in depression, while physical exercise significantly reverted them. As previously reported, chronic stress induced inflammation in the affected hippocampus in parallel with defects of adult neurogenesis, on the other hand physical exercise ameliorated those pathological conditions of the bran in depression. In conclusion, this study demonstrated the implications of impairment of the hippocampal SWRs and theta rhythms in the etiology of depression and their usefulness as diagnostic markers of depression.

neuroscience↗

bioRxiv2020

Brain state-dependent cortico-hippocampal network dynamics are modulated by postnatal stimuli

Neurons in the cerebral cortex and hippocampus discharge synchronously in a brain state-dependent manner to transfer information. Published studies have highlighted the temporal coordination of neuronal activities between the hippocampus and a cortical area, however, how the spatial extent of cortex activity relates to hippocampal activity remains largely unknown. We imaged macroscopic cortical activity while recording hippocampal local field potentials in unanesthetized GCaMP-expressing transgenic mice. We found that cortical activity elevates before and after hippocampal sharp wave ripples (SWR). SWR-associated cortical activities occurred predominantly in vision-related regions including visual, retrosplenial and prefrontal cortex. While pre-SWR cortical activities were frequently observed in awake and sleep states, post-SWR cortical activity decreased significantly in sleep. During hippocampal theta oscillation states, phase-locked oscillations of calcium activity was observed throughout the entire cortex state. Environmental effects on cortico-hippocampal dynamics were also assessed by comparing mice reared in an enriched environment (ENR) or under isolated conditions (ISO). In both SWR and theta oscillations, mice reared in an isolated condition exhibited clearer brain state-dependent dynamics than those reared in an enriched environment. Our data demonstrate that the cortex and hippocampus exhibit heterogeneous activity patterns that characterize brain states, and postnatal experience plays a significant role in modulating these patterns. Significant StatementThe hippocampus is a center for memory formation. However, the memory formed in the hippocampus is not stored forever, but gradually transferred into the cerebral cortex. As an underlying mechanism, phase-locked synchronized activities between the cortex and hippocampus has been hypothesized. However, spatio-temporal dynamics between hippocampus and whole cortical areas remained mostly unknown. We measured cortical calcium activities with hippocampal electroencephalogram (EEG) simultaneously, and found that the activities of widespread cortical areas are temporally associated with hippocampal EEG. The cortico-hippocampal dynamics is primarily regulated by animal awake/sleep state. Even if similar EEG patters were observed, temporal dynamics between the cortex and hippocampus exhibit distinct patterns between awake and sleep period. In addition, animals postnatal experience modulates the dynamics.

neuroscience↗