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Oomoto, I.

Publications and source records attributed to Oomoto, I..

5 recordsLinked to original sources

Meso2EM: a cross-scale CLEM workflow linking mesoscale functional imaging to targeted electron microscopy

Meso2EM is a correlative light and electron microscopy workflow that transfers neurons selected from mesoscale functional images to targeted electron microscopy. We recorded Ca{superscript 2} signals from layer 2/3 neurons across a contiguous 3 x 3 mm cortical field in awake mice and reidentified a selected neuron after fixation and tangential sectioning. Lectin-labeled vascular architecture served as a shared landmark across in vivo two-photon imaging, confocal microscopy, laboratory micro-CT of resin-embedded tissue, and block-surface scanning electron microscopy, guiding focused-ion-beam scanning electron microscopy to the target cell body. The same progressive-targeting principle also supported serial ATUM-SEM reconstruction of an in vivo-tracked dendrite and serial transmission electron microscopy of optically selected dendrites from a patch-clamp-recorded Martinotti cell. Meso2EM therefore provides a practical route for preserving target identity across large changes in scale and specimen state while restricting electron-microscopy acquisition to a selected region.

neuroscience↗

Multi-area single-cell calcium imaging dataset of the mouse cortex across wakefulness, sleep, and anesthesia

We present a reusable dataset of neuronal population activity from multiple cortical areas, recorded from layers 2/3 of the mouse cortex at single-cell resolution during wakefulness, natural sleep (including NREM and REM sleep), and isoflurane anesthesia. Using wide-field two-photon microscopy, we recorded approximately 4,000 to 10,000 neurons per session at 7.65 Hz and provided the spatial coordinates of individual neurons. The repository provides both processed datasets and the corresponding raw imaging movies (TIFF) and electrophysiological recordings (MATLAB format). Processed data are distributed in MATLAB format and include {Delta} F/F fluorescence signals, deconvolved spike estimates, Gaussian-smoothed spike estimates, behavioral state annotations, and metadata. This dataset supports reuse in studies of cortical population dynamics, brain-state-dependent activity, and spatially distributed neuronal organization. It should also be useful for method development, benchmarking, and comparative analyses of large-scale neuronal activity across physiological and pharmacological brain states.

neuroscience↗

Repetitive Hibernation-Like State Suppresses the Progression of Amyloid Pathology

Alzheimers disease (AD) is characterized by the gradual accumulation of amyloid pathology before the onset of cognitive impairment, yet effective strategies to alter disease progression remain limited. Here, we tested whether induction of a hibernation-like physiological state can slow amyloid pathology in an AD mouse model. To achieve sustained effects, we developed a protocol for repeated induction of a hypometabolic/hypothermic state and found that it significantly slowed plaque accumulation in a duration-dependent manner. This intervention also attenuated neuroinflammation and the formation of dystrophic neurites associated with plaques. Notably, this approach does not target specific molecular pathways but instead modulates global brain state. Our findings establish a proof-of-concept for a brain-state- based therapeutic paradigm for modifying disease progression in AD.

neuroscience↗

Single-cell resolution functional networks during sleep aresegregated into spatially intermixed modules

The common neural mechanisms underlying the reduction of consciousness during sleep and anesthesia remain unclear. Previous studies have examined changes in network structure only using recordings with limited spatial resolution, which has hindered the investigation of the critical spatial scales from the micro (single neurons) to the meso (groups of neurons) for the reduction of consciousness. To address this issue, by leveraging fast, single-cell resolution, and wide-field two-photon microscopy, we recorded calcium signals from approximately 10,000 neurons across multiple cortical regions in awake, sleeping, and anesthetized mice. This single-cell resolution data enabled us to investigate the scales at which changes in network structure compared to an awake state are commonly observed during sleep and anesthesia. We found that at the single-cell scale, both sleep and anesthesia exhibited higher network modularity, indicating a segregated network, compared to an awake state. Despite this segregation, modules were spatially intermixed in all three states. In contrast, at the mesoscale, there were no consistent differences in modularity between states, and modules were spatially localized. Our multi-scale analysis provides novel insights into the cellular-scale organization of functional networks commonly associated with the reduction of consciousness and highlights a scale-dependent organization of network structures.

neuroscience↗

Schizophrenia and autism-associated mutations and disrupted m6A signal by YTHDF1 cause defects in microtubule function and neurodevelopment

Subcellular mRNA localization and local translation are crucial for spatially regulated gene expression in neurons. However, the precise mechanisms governing the selective transport and translation of mRNAs contributing to processes such as axonal growth and branching are only partially understood. Here, we present evidence of N6-methyladenosine (m6A)-mediated translational control of the RNA-binding protein, APC, influencing cytoskeletal dynamics at the growth cone. Our findings demonstrate that m6A modifications occur on Apc mRNA, facilitating its recognition by YTHDF1 to promote APC translation in neuronal somata. Additionally, we observe that disrupting the m6A pathway impairs the transport and local translation of {beta}-actin mRNA in the axon and growth cones, a deficiency that can be rescued by the exogenous expression of APC protein in cultured neurons. Furthermore, we establish the essential role of YTHDF1 in axon development, particularly in callosal projection neurons during cortical development. Our findings suggest a novel mechanism involving m6A-mediated regulation of APC protein translation, linking epitranscriptomics to axonal mRNA targeting, cytoskeletal dynamics, and axon development.

neuroscience↗