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Umeda T.,National Institute for Physiological science NIPS | Umeda T.,Yokohama City University | Funakoshi K.,Yokohama City University
Neuroscience Research | Year: 2014

It is well recognized that a juvenile brain is more plastic than an adult brain and often undergoes better functional recovery following cortical injury. Infants treated with hemispherectomy to cure intractable epilepsy often exhibit restored normal motor function in the extremities contralateral to the lesion. Neuronal mechanisms of functional recovery after such a large cortical damage at a young age have been studied using animals with a similar lesion, hemidecortication. In such animals, descending pathways from the undamaged sensorimotor cortex to the ipsilateral forelimb motoneurons are reorganized as restoring normal motor function of the forelimb contralateral to the injury. Similar aberrant pathways from the motor cortex to the ipsilateral motoneurons are also generated following suppression of cortical activity in the other hemisphere, suggesting the development of contralateral connections in an activity-dependent manner in normal animals. Thus, formation of ipsilateral descending pathways following neonatal hemidecortication might be due to a loss of balance in cortical activity between the two hemispheres. Studies using animal models of neonatal cortical injury can reveal mechanisms of neural development and may help to establish therapeutic strategies to facilitate recovery from human juvenile cortical injury. © 2013 Elsevier Ireland Ltd and the Japan Neuroscience Society. Source


Satake S.I.,National Institute for Physiological science NIPS | Satake S.I.,Graduate University for Advanced Studies | Inoue T.,Okayama University | Imoto K.,National Institute for Physiological science NIPS | Imoto K.,Graduate University for Advanced Studies
Cerebellum | Year: 2016

The number of synaptic vesicles released during fast release plays a major role in determining the strength of postsynaptic response. However, it remains unresolved how the number of vesicles released in response to action potentials is controlled at a single synapse. Recent findings suggest that the Cav2.1 subtype (P/Q-type) of voltage-gated calcium channels is responsible for inducing presynaptic multivesicular release (MVR) at rat cerebellar glutamatergic synapses from granule cells to molecular layer interneurons. The topographical distance from Cav2.1 channels to exocytotic Ca2+ sensors is a critical determinant of MVR. In physiological trains of presynaptic neurons, MVR significantly impacts the excitability of postsynaptic neurons, not only by increasing peak amplitude but also by prolonging decay time of the postsynaptic currents. Therefore, MVR contributes additional complexity to neural encoding and processing in the cerebellar cortex. © 2015, Springer Science+Business Media New York. Source


Inagaki-Ohara K.,University of Ryukyus | Inagaki-Ohara K.,National Institute for Physiological science NIPS | Inagaki-Ohara K.,Research Center for Hepatitis and Immunology | Mayuzumi H.,University of Ryukyus | And 7 more authors.
Oncogene | Year: 2014

Leptin acts on its receptor (ObR) in the hypothalamus to inhibit food intake and energy expenditure. Leptin and ObR are also expressed in the gastrointestinal tract; however, the physiological significance of leptin signaling in the gut remains uncertain. Suppressor of cytokine signaling 3 (SOCS3) is a key negative feedback regulator of ObR-mediated signaling in the hypothalamus. We now show that gastrointestinal epithelial cell-specific SOCS3 conditional knockout (T3b-SOCS3 cKO) mice developed gastric tumors by enhancing leptin production and the ObRb/signal transducer and activator of transcription 3 (STAT3) signaling pathway. All T3b-SOCS3 cKO mice developed tumors in the stomach but not in the bowels by 2 months of age, even though the SOCS3 deletion occurred in both the epithelium of stomach and bowels. The tumors developed in the absence of the inflammatory response and all cKO mice died within 6 months. These tumors displayed pathology and molecular alterations, such as an increase in MUC2 (Mucin 2, oligomeric mucus/gel-forming) and TFF3 (trefoil factor 3), resembling human intestinal-type gastric tumors. Administration of antileptin antibody to T3b-SOCS3 cKO mice reduced hyperplasia of gastric mucosa, which is the step of the initiation of gastric tumor. These data suggest that SOCS3 is an antigastric tumor gene that suppresses leptin overexpression and ObRb/STAT3 hyperactivation, supporting the hypothesis that the leptin/ObRb/STAT3 axis accelerates tumorigenesis and that it may represent a new therapeutic target for the treatment of gastric cancer. © 2014 Macmillan Publishers Limited. Source


Umeda T.,National Institute for Physiological science NIPS | Seki K.,National Institute for Physiological science NIPS | Seki K.,National Institute of Neuroscience | Seki K.,Japan Science and Technology Agency | And 7 more authors.
PLoS ONE | Year: 2012

Various peripheral receptors provide information concerning position and movement to the central nervous system to achieve complex and dexterous movements of forelimbs in primates. The response properties of single afferent receptors to movements at a single joint have been examined in detail, but the population coding of peripheral afferents remains poorly defined. In this study, we obtained multichannel recordings from dorsal root ganglion (DRG) neurons in cervical segments of monkeys. We applied the sparse linear regression (SLiR) algorithm to the recordings, which selects useful input signals to reconstruct movement kinematics. Multichannel recordings of peripheral afferents were performed by inserting multi-electrode arrays into the DRGs of lower cervical segments in two anesthetized monkeys. A total of 112 and 92 units were responsive to the passive joint movements or the skin stimulation with a painting brush in Monkey 1 and Monkey 2, respectively. Using the SLiR algorithm, we reconstructed the temporal changes of joint angle, angular velocity, and acceleration at the elbow, wrist, and finger joints from temporal firing patterns of the DRG neurons. By automatically selecting a subset of recorded units, the SLiR achieved superior generalization performance compared with a regularized linear regression algorithm. The SLiR selected not only putative muscle units that were responsive to only the passive movements, but also a number of putative cutaneous units responsive to the skin stimulation. These results suggested that an ensemble of peripheral primary afferents that contains both putative muscle and cutaneous units encode forelimb joint kinematics of non-human primates. © 2012 Umeda et al. Source


Shimada K.,National Institute for Physiological science NIPS | Shimada K.,Graduate University for Advanced Studies | Shimada K.,University of Fukui | Hirotani M.,National Institute for Physiological science NIPS | And 13 more authors.
Neuroscience | Year: 2015

This functional magnetic resonance imaging (fMRI) study investigated the brain regions underlying language task performance in adult second language (L2) learners. Specifically, we identified brain regions where the level of activation was associated with L2 fluency levels. Thirty Japanese-speaking adults participated in the study. All participants were L2 learners of English and had achieved varying levels of fluency, as determined by a standardized L2 English proficiency test, the Versant English Test (. Pearson Education Inc., 2011). When participants performed the oral sentence building task from the production tasks administered, the dorsal part of the left inferior frontal gyrus (dIFG) showed activation patterns that differed depending on the L2 fluency levels: The more fluent the participants were, the more dIFG activation decreased. This decreased activation of the dIFG might reflect the increased automaticity of a syntactic building process. In contrast, when participants performed an oral story comprehension task, the left posterior superior temporal gyrus (pSTG) showed increased activation with higher fluency levels. This suggests that the learners with higher L2 fluency were actively engaged in post-syntactic integration processing supported by the left pSTG. These data imply that L2 fluency predicts neural resource allocation during language comprehension tasks as well as in production tasks. This study sheds light on the neural underpinnings of L2 learning by identifying the brain regions recruited during different language tasks across different modalities (production vs. comprehension). © 2015 The Authors. Source

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