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Tainaka, K.

Publications and source records attributed to Tainaka, K..

7 recordsLinked to original sources

A preoptic circuit triggers rewarming from torpor

Torpor is an adaptive hypometabolic state that enables homeotherm to survive periods of energetic challenge. This strategy ranges from short bouts of daily torpor to prolonged hibernation. During torpor, animals markedly suppress metabolic rate, body temperature, heart rate, and respiration, while retaining the ability to rewarm. Torpor therefore comprises two critical transitions -entry into a hypometabolic state and active rewarming-both essential for organismal viability. Although neural mechanisms controlling torpor entry have begun to emerge, the circuits that initiate active rewarming and restore euthermia remain poorly defined. Here we identify corticotropin-releasing hormone (Crh)-expressing neurons in the anterodorsal preoptic area (ADP) as a key population for rewarming from fasting-induced torpor in mice. These neurons become active around natural rewarming and are selectively required to limit the depth and duration of torpor. Unlike pathways mediating acute cold defence, stress hyperthermia, or LPS-induced fever, this circuit is dedicated to promoting timely recovery to euthermia. Closed-loop optogenetic activation of ADPCrh neurons during torpor entry rapidly initiates rewarming, and thermographic recordings show that brown adipose tissue (BAT) thermogenesis precedes locomotor arousal. ADPCrh neurons are predominantly GABAergic and project monosynaptically to the lateral preoptic area, whose terminal activation is sufficient to increase body temperature and locomotor activity. Finally, we find robust activation of ADPCrh neurons during rewarming in a hibernator, suggesting conserved logic for exiting deep torpor. Together, our results define a discrete preoptic circuit that drives recovery from torpor and provide a framework for understanding and potentially controlling timely rewarming from profound hypothermia.

neuroscience↗

A practical pipeline for volume rendering of trillion-voxel tomographic data

Recent advancements in tomography produce imaging data of geological materials (rocks and fossils) at trillion-voxel scales with multi-channels. Such high-resolution datasets are potentially keys to unveil evolutionary biological information with various shapes and sizes that have not been ever discovered. Volume rendering is an ideal visualization approach for them because it treats all voxels without relying on user-defined surface boundaries. However, these large-scale real-world tomographic data have rarely been volume-rendered at their native resolution, limiting the examination of rich morphological information. Here, we demonstrate a de facto standard volume-rendering pipeline running on a graphical processing unit (GPU)-equipped supercomputing system toward multi-channel, trillion-voxel tomographic data. Our workflow preserves original resolution, capturing detailed morphological information spanning microscopic to macroscopic scales. Systematic comparison of node types shows that GPU memory, rather than host memory, is the primary bottleneck. Our results establish a baseline for large-scale, multi-channel volume rendering of real tomographic data and demonstrate its applicability to geological samples. This work is presented as a practical demonstration of large-scale volume visualization.

paleontology↗

Artificial Intelligence-driven Whole-brain Cell Mapping with Highly Multiplexed In Situ Hybridization

Recent advances in three-dimensional single-cell-resolution imaging have begun to link organ-wide and cellular level research in development and disease research. Harnessing the power of whole-mount cell staining and tissue-clearing, it became possible to quantify the cell populations throughout an intact organ. While powerful, whole-organ imaging remains limited by the inability to stain a broad range of molecular markers simultaneously and by the lack of an analytical scheme to precisely quantify the cell population. Here, we present a highly multiplexed whole-mount staining technique, utilizing the repeated application of fluorescent in situ hybridization. This technique, termed mFISH3D, was designed by extensively dissecting the chemical basis of hybridization reactions in fixed tissue. mFISH3D enabled the visualization of 10 types of mRNAs in an intact mouse brain and has been demonstrated in various biological specimens including the human brain. To achieve unprecedented levels of accuracy in spatial cell mapping, we developed artificial intelligence (AI)-driven workflow using self-supervised learning, significantly reducing the need for extensive manual annotations. The integration of mFISH3D with our AI solution sets a standard for high-dimensional tissue analysis, provides a new systematic framework for analyzing complex cellular ecosystems and enables comprehensive investigation of selective cellular vulnerabilities in diseases.

neuroscience↗

Renin Cells Drive Kidney Neurovascular Development and Arterial Remodeling when Renin Activity is Deficient

Renin cells synthesize and release the hormone-enzyme renin to regulate blood pressure and fluid-electrolyte homeostasis. Their function and identity depend on communication with surrounding cells and nerve fibers within complex kidney structure. Because renin cells are rare -0.01 % of kidney cells-conventional histological approaches cannot capture their interaction with nerve fibers and surrounding cells within the nephron and its vasculature. Using a novel ultrabright renin cell-specific tdTomato reporter mouse, high-resolution 3D imaging, and single-cell RNA-Seq, we mapped the interactions of renin cells with growing axons during normal kidney vascular development, in response to threats to homeostasis, and a severe arterial disease caused by a defective renin enzyme. During embryonic kidney development, stromal and renin cell progenitors assemble the arterioles, express axon attractants and neurotrophins that establish the precise innervation of renin cells and arterioles in a centrifugal pattern. Hypotension and sodium depletion led to an increase in the volume and number of renin cells along the arterioles. Renin enzymatic deficiency led to hypertrophy and endocrine transformation of renal arterioles, aberrant axon sprouting and sympathetic hyperinnervation suggesting a feed-forward mechanism whereby renin cells and axons co-induce each other, orchestrate neurovascular development and arteriolar remodeling when renin cells are over stimulated.

developmental biology↗

Cerebrospinal fluid-contacting neuron tracing reveals structural and functional connectivity for locomotion in the mouse spinal cord

Cerebrospinal fluid-contacting neurons (CSF-cNs) are enigmatic mechano- or chemosensory cells lying along the central canal of the spinal cord. Recent studies in zebrafish larvae and lampreys have shown that CSF-cNs control postures and movements via spinal connections. However, the structures, connectivity, and functions in mammals remain largely unknown. Here we developed a method to genetically target mouse CSF-cNs that highlighted structural connections and functions. We first found that intracerebroventricular injection of adeno-associated virus with a neuron-specific promoter and Pkd2l1-Cre mice specifically labeled CSF-cNs. Single-cell labeling of 71 CSF-cNs revealed rostral axon extensions of over 1800 m in unmyelinated bundles in the ventral funiculus and terminated on CSF-cNs to form a recurrent circuitry, which was further determined by serial electron microscopy and electrophysiology. CSF-cNs were also found to connect with axial motor neurons and premotor interneurons around the central canal and within the axon bundles. Chemogenetic CSF-cNs inactivation reduced speed and step frequency during treadmill locomotion. Our data revealed the basic structures and connections of mouse CSF-cNs to control spinal motor circuits for proper locomotion. The versatile methods developed in this study will contribute to further understanding of CSF-cNs functions in mammals.

neuroscience↗

Small Vessel Diseases: 3D Characteristics of the Vasculature and White Matter

Cerebral small vessel disease (SVD) is associated with white matter hyperintensities (WMHs), thereby contributing to vascular dementia and movement disorder. However, the pathomechanisms responsible for WMH-related small vessel degeneration remain poorly understood due to the technical limitations of current methods. The aim of this study was to clarify the 2- and 3-dimensional (2D and 3D) pathological features of small vessels and white matter (WM) in the brains of patients with cerebral autosomal dominant arteriopathy with subcortical infarcts and leukoencephalopathy (CADASIL), HTRA1-autosomal dominant disease (HTRA1-AD) and sporadic SVD (sSVD). From a cohort of 86 consecutive autopsied patients with SVDs, we retrieved those with genetically confirmed CADASIL and HTRA1-AD (three and three, respectively), and four with sSVD. We quantitatively evaluated WM and vascular changes in the frontal portion of the centrum semiovale and temporal lobe using conventional 2D and chemically cleared 3D analytical methods with light-sheet fluorescence microscopy. Quantitatively, the WM pathology, including the density of myelin, axons and gliosis, was most severe in CADASIL, but unexpectedly sSVD was second in order of severity, followed by HTRA1-AD. The density of clasmatodendrocytes, known to be irreversibly injured astrocytes, was considerably highest in HTRA1-AD. The vascular pathology, including arteriole and capillary sclerosis and the extent of the perivascular space, was most severe in CADASIL, whereas the density of smooth muscle actin (SMA) positivity was most decreased in HTRA1-AD. 3D immunohistochemistry for SMA demonstrated two distinct patterns of SMA loss within the vessels: (1) CADASIL and sSVD: diffuse loss, being prominent in small branches, (2) HTRA1-AD: selective loss in main branches. Overall, the extent of WM and vascular degeneration is most severe in CADASIL, whereas SMA loss is most evident in HTRA1-AD. These differences in the size and distribution of affected vessels may be related to the heterogeneous WM pathology and underlying pathomechanisms of SVD.

pathology↗

Three-dimensional understanding of the morphological complexity of the human uterine endometrium

SummaryThe histological basis of the human uterine endometrium has been established by 2D observation. However, the fundamental morphology of endometrial glands is not sufficiently understood because these glands have complicated winding and branching patterns. To construct a big picture of endometrial gland structure, we performed tissue-clearing-based 3D imaging of human uterine endometrial tissue. Our 3D immunohistochemistry and 3D layer analyses revealed that endometrial glands formed a plexus network in the stratum basalis, similar to the rhizome of grass. We then extended our method to assess the 3D morphology of adenomyosis, a representative “endometrium-related disease”, and observed 3D morphological features including direct invasion of endometrial glands into the myometrium and an ant colony-like network of ectopic endometrial glands within the myometrium. Thus, 3D analysis of the human endometrium and endometrium-related diseases will be a promising approach to better understand the pathologic physiology of the human endometrium.Competing Interest StatementThe authors have declared no competing interest.View Full Text

pathology↗