記述言語：英語   掲載種別：研究論文（学術雑誌）  

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 μm 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-cN functions in mammals.

DOI： 10.7554/eLife.83108

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記述言語：英語   掲載種別：研究論文（学術雑誌）   出版者・発行元：Frontiers Media SA  

The corticospinal tract (CST) is an essential neural pathway for reorganization that recovers motor functions after brain injuries such as stroke. CST comprises multiple pathways derived from different sensorimotor areas of the cerebral cortex; however, the patterns of reorganization in such complex pathways postinjury are largely unknown. Here we comprehensively examined the rewiring patterns of the CST pathways of multiple cerebral origins in a mouse stroke model that varied in size and location in the sensorimotor cortex. We found that spared contralesional motor and sensory CST axons crossed the midline and sprouted into the denervated side of the cervical spinal cord after stroke in a large cortical area. In contrast, the contralesional CST fibers did not sprout in a small stroke, whereas the ipsilesional axons from the spared motor area grew on the denervated side. We further showed that motor and sensory CST axons did not innervate the projecting areas mutually when either one was injured. The present results reveal the basic principles that generate the patterns of CST rewiring, which depend on stroke location and CST subtype. Our data indicate the importance of targeting different neural substrates to restore function among the types of injury.

DOI： 10.3389/fnins.2021.737034

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記述言語：英語   掲載種別：研究論文（学術雑誌）   出版者・発行元：Society for Neuroscience  

Abstract

Olfactory sensory neurons (OSNs) expressing same-type odorant receptors typically project to a pair of glomeruli in the medial and lateral sides of the olfactory bulbs (OBs) in rodents. This multiple glomerular representation of homologous inputs is considered to have more important functional roles for odor information processing than the redundant backup system. However, a consensus idea is lacking and this hinders interpretation of the phenomenon. In addition, the shared and unique odorant response properties of the homologous glomeruli remain unclear because the majority of medial glomeruli are hidden in the septal OB, and thus it is difficult to directly compare them. OSNs, which express trace amine-associated odorant receptors (TAARs), were recently identified that project to a pair of glomeruli uniquely located in the dorsal OB. In this study, we measured the odorant-induced calcium responses of homologous pairs of TAAR glomeruli simultaneously in anesthetized mice and directly compared their response patterns. We found that they exhibited similar temporal response patterns and could not find differences in onset latency, rise time, decay time, or response amplitude. However, the medial glomeruli had significantly larger respiration-locked calcium fluctuations than the lateral glomeruli. This trend was observed with/without odorant stimulation in postsynaptic neurons of GABAergic, dopaminergic, and mitral/tufted cells, but not in presynaptic olfactory sensory axon terminals. This indicates that, at least in these TAAR glomeruli, the medial rather than the lateral OB map enhances the respiration-locked rhythm and transfers this information to higher brain centers.

DOI： 10.1523/eneuro.0449-19.2020

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記述言語：英語   掲載種別：研究論文（学術雑誌）   出版者・発行元：Society for Neuroscience  

Abstract

Odor information is transmitted from olfactory sensory neurons to principal neurons at the glomeruli of the olfactory bulb. The intraglomerular neuronal circuit also includes hundreds of interneurons referred to as juxtaglomerular (JG) cells. Stimulus selectivity is well correlated among many JG cells that are associated with the same glomerulus, consistent with their highly homogeneous sensory inputs. However, much less is known about the temporal aspects of their activity, including the temporal coordination of their odor-evoked responses. As many JG cells within a glomerular module respond to the same stimulus, the extent to which their activity is temporally aligned will affect the temporal profile of their population inhibitory inputs. Using random-access high-speed two-photon microscopy, we recorded the odor-evoked calcium transients of mouse JG cells and compared the onset latency and rise time among neurons putatively associated with the same and different glomeruli. Whereas the overall onset latencies of odor-evoked transients were distributed across a ∼150 ms time window, those from cells putatively associated with the same glomerulus were confined to a much narrower window of several tens of milliseconds. This result suggests that onset latency primarily depends on the associated glomerulus. We also observed glomerular specificity in the rise time. The glomerulus-specific temporal pattern of odor-evoked activity implies that the temporal patterns of inputs from the intraglomerular circuit are unique to individual glomerulus–odor pairs, which may contribute to efficient shaping of the temporal pattern of activity in the principal neurons.

DOI： 10.1523/eneuro.0387-18.2019

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記述言語：英語   掲載種別：研究論文（学術雑誌）  

Osteopontin (OPN) is involved in cell proliferation, migration, inflammation, and tumor progression in various tissues. OPN induces stemness by interacting with CD44, but the functional relevance of OPN-mediated interferon (IFN) signaling and hepatitis C virus (HCV) replication in stem cell populations remains unclear. In this study, we investigated the effect of OPN on HCV replication and IFN signaling in cancer stem cells (CSCs) positive for epithelial cell adhesion molecule (EpCAM) and CD44. We show that the EpCAM+/CD44+ CSCs show marked HCV replication when compared to EpCAM-/CD44- cells. In addition, OPN significantly enhances this HCV replication in EpCAM+/CD44+ CSCs and markedly suppresses IFN-stimulated gene expression. The GSK-3β inhibitor BIO increases the EpCAM+/CD44+ CSC population and OPN expression and impairs IFN signaling via STAT1 degradation. Taken together, our data suggest that OPN enhances HCV replication in the EpCAM+/CD44+ CSCs, while it also negatively regulates the IFN signaling pathway via inhibition of STAT1 phosphorylation and degradation. Therefore, OPN may represent a novel therapeutic target for treating HCV-related hepatocellular carcinoma.

DOI： 10.1038/s41598-018-31421-6

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担当区分：筆頭著者   記述言語：英語   掲載種別：研究論文（学術雑誌）  

DOI： 10.1016/j.febslet.2015.08.024

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担当区分：筆頭著者   記述言語：英語   掲載種別：研究論文（学術雑誌）  

DOI： 10.1038/cdd.2014.207

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担当区分：筆頭著者   記述言語：英語   掲載種別：研究論文（学術雑誌）  

DOI： 10.1111/gtc.12170

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記述言語：英語   掲載種別：研究論文（学術雑誌）  

DOI： 10.1111/gtc.12135

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記述言語：英語   掲載種別：研究論文（学術雑誌）  

DOI： 10.3324/haematol.2011.058529

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担当区分：筆頭著者   記述言語：英語   掲載種別：研究論文（学術雑誌）  

DOI： 10.1111/j.1365-2443.2010.01465.x

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記述言語：英語   掲載種別：研究論文（学術雑誌）  

DOI： 10.1007/s11248-008-9191-6

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記述言語：英語   掲載種別：研究論文（学術雑誌）  

DOI： 10.1007/s11248-008-9191-6

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担当区分：筆頭著者   記述言語：英語   掲載種別：研究論文（学術雑誌）  

DOI： 10.1016/j.mcn.2008.08.003

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記述言語：英語   掲載種別：研究論文（学術雑誌）  

DOI： 10.1016/j.neulet.2007.09.057

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記述言語：英語   掲載種別：研究論文（学術雑誌）  

DOI： 10.1111/j.1471-4159.2006.03835.x

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記述言語：英語   掲載種別：研究論文（学術雑誌）   出版者・発行元：5  

DOI： 10.1111/j.1471-4159.2006.03835.x

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担当区分：筆頭著者   記述言語：英語   掲載種別：研究論文（学術雑誌）  

DOI： 10.1016/j.bbrc.2005.10.052

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記述言語：英語   掲載種別：研究論文（学術雑誌）  

DOI： 10.1074/jbc.M505241200

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記述言語：英語   掲載種別：研究論文（学術雑誌）  

DOI： 10.1007/s00427-004-0442-0

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記述言語：英語   出版者・発行元：(一社)日本認知症学会  

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記述言語：英語   出版者・発行元：Institute of Science and Engineering, Kanazawa University = 金沢大学  

We previously reported that the structurally related JNK scaffolding proteins JSAP1 and JLP play functionally redundant and key roles in maintaining mouse cere-bellar Purkinje cell (PC) survival, which may be related to their regulation of axonal transport. The JSAP1 and JLP proteins are also widely expressed in other cell types throughout the brain. Notably, in the cerebellum, JSAP1 is abundantly expressed in the pinceau, a cluster of basket cell (BC) axons and termini that surround the PC axon initial segment. Thus, it is possible that BC-expressed JSAP1 plays a role in PC survival. To investigate this possibility, we generated and analyzed mice containing a PC/BC-specific double knockout (DKO) of Jsap1 and Jlp (Jsap1:Jlp cDKO mice). These mice exhibited PC axonal dystrophy, followed by progressive PC loss, consistent with the phenotypes previously reported for PC-specific Jsap1 and Jlp DKO mice. Furthermore, we found that the phenotypes of Jsap1:Jlp cDKO PCs were rescued by PC-specific transgenic expression of JSAP1. Taken together, these results indicate that BC-expressed JSAP1 plays little or no role in PC survival, and that PC-expressed JSAP1 and JLP play cell-autonomous roles in preventing PC degeneration.

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担当区分：筆頭著者  

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記述言語：英語   出版者・発行元：金沢大学がん研究所  

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