Research activity information

• 2013 日本生理学会奨励賞

  橘吉寿


• 2006 難病医学研究財団 医学研究奨励賞

  橘吉寿


• 1999 デンツプライ歯学賞

  橘吉寿

• Cerebellar Nuclei Receiving Orofacial Proprioceptive Signals through the Mossy Fiber Pathway from the Supratrigeminal Nucleus in Rats.

  Yumi Tsutsumi, Yayoi Morita, Fumihiko Sato, Takahiro Furuta, Katsuro Uchino, Jaerin Sohn, Tahsinul Haque, Yong Chul Bae, Hitoshi Niwa, Yoshihisa Tachibana, Atsushi Yoshida

  Proprioception from muscle spindles is necessary for motor function executed by the cerebellum. In particular, cerebellar nuclear neurons that receive proprioceptive signals and send projections to the lower brainstem or spinal cord play key roles in motor control. However, little is known about which cerebellar nuclear regions receive orofacial proprioception. Here, we investigated projections to the cerebellar nuclei from the supratrigeminal nucleus (Su5), which conveys the orofacial proprioception arising from jaw-closing muscle spindles (JCMSs). Injections of an anterograde tracer into the Su5 resulted in a large number of labeled axon terminals bilaterally in the dorsolateral hump (IntDL) of the cerebellar interposed nucleus (Int) and the dorsolateral protuberance (MedDL) of the cerebellar medial nucleus. In addition, a moderate number of axon terminals were ipsilaterally labeled in the vestibular group Y nucleus (group Y). We electrophysiologically detected JCMS proprioceptive signals in the IntDL and MedDL. Retrograde tracing analysis confirmed bilateral projections from the Su5 to the IntDL and MedDL. Furthermore, anterograde tracer injections into the external cuneate nucleus (ECu), which receives other proprioceptive input from forelimb/neck muscles, resulted in only a limited number of ipsilaterally labeled terminals, mainly in the dorsomedial crest of the Int and the group Y. Taken together, the Su5 and ECu axons almost separately terminated in the cerebellar nuclei (except for partial overlap in the group Y). These data suggest that orofacial proprioception is differently processed in the cerebellar circuits in comparison to other body-part proprioception, thus contributing to the executive function of orofacial motor control.

  Sep. 2023, Cerebellum (London, England), English, International magazine

  Scientific journal


• Regulation of lipid synthesis in myelin modulates neural activity and is required for motor learning

  Daisuke Kato, Yuki Aoyama, Kazuki Nishida, Yutaka Takahashi, Takumi Sakamoto, Ikuko Takeda, Tsuyako Tatematsu, Shiori Go, Yutaro Saito, Shiho Kunishima, Jinlei Cheng, Lingnan Hou, Yoshihisa Tachibana, Shouta Sugio, Reon Kondo, Fumihiro Eto, Shumpei Sato, Andrew J Moorhouse, Ikuko Yao, Kenji Kadomatsu, Mitsutoshi Setou, Hiroaki Wake

  Jul. 2023, Glia

  [Refereed]

  Link to Kobe Univ. Repository (Kernel)


• Emotional modulation of cortical activity during gum chewing: A functional near-infrared spectroscopy study

  Yoko Hasegawa, Ayumi Sakuramoto, Tatsuya Suzuki, Joe Sakagami, Masako Shiramizu, Yoshihisa Tachibana, Hiromitsu Kishimoto, Yumie Ono, Takahiro Ono

  Distinct brain regions are known to be associated with various emotional states. Cortical activity may be modulated by emotional states that are triggered by flavors during food intake. We examined cortical activity during chewing with different flavors and assessed the emotional modulation of cortical activity using multichannel near-infrared spectroscopy. Thirty-six right-handed volunteers participated in this crossover trial. The participants experienced positive and negative emotions from chewing flavorful (palatable) or less flavorful (unpalatable) gums, respectively for 5 min. Participants rated the taste, odor, and deliciousness of each gum using a visual analog scale. Bilateral hemodynamic responses in the frontal and parietal lobes, bilateral masseter muscle activation, and heart rate were measured during gum chewing. Changes in all measured data during gum chewing were also evaluated. The ratings of the tastes and odors of each gum significantly differed among the participants (P < 0.001). Hemodynamic response changes were significantly elevated in the bilateral primary sensorimotor cortex during gum-chewing, in comparison to resting. The difference in hemodynamic responses between palatable and unpalatable gum conditions was detected in the left frontopolar/dorsolateral prefrontal cortex. Muscle activation and heart rate were not significantly different between different gum types. Our findings indicate that differential processing in the left prefrontal cortex might be responsible for the emotional states caused by palatable and unpalatable foods.

  Frontiers Media SA, Nov. 2022, Frontiers in Neuroscience, 16

  Scientific journal


• The Cerebellar Cortex Receives Orofacial Proprioceptive Signals from the Supratrigeminal Nucleus via the Mossy Fiber Pathway in Rats.

  Yumi Tsutsumi, Fumihiko Sato, Takahiro Furuta, Katsuro Uchino, Masayuki Moritani, Yong Chul Bae, Takafumi Kato, Yoshihisa Tachibana, Atsushi Yoshida

  Proprioceptive sensory information from muscle spindles is essential for the regulation of motor functions. However, little is known about the motor control regions in the cerebellar cortex that receive proprioceptive signals from muscle spindles distributed throughout the body, including the orofacial muscles. Therefore, in this study, we investigated the pattern of projections in the rat cerebellar cortex derived from the supratrigeminal nucleus (Su5), which conveys orofacial proprioceptive information from jaw-closing muscle spindles (JCMSs). Injections of an anterograde tracer into the Su5 revealed that many bilateral axon terminals (rosettes) were distributed in the granular layer of the cerebellar cortex (including the simple lobule B, crus II and flocculus) in a various sized, multiple patchy pattern. We could also detect JCMS proprioceptive signals in these cerebellar cortical regions, revealing for the first time that they receive muscle proprioceptive inputs in rats. Retrograde tracer injections confirmed that the Su5 directly sends outputs to the cerebellar cortical areas. Furthermore, we injected an anterograde tracer into the external cuneate nucleus (ECu), which receives proprioceptive signals from the forelimb and neck muscle spindles, to distinguish between the Su5- and ECu-derived projections in the cerebellar cortex. The labeled terminals from the ECu were distributed predominantly in the vermis of the cerebellar cortex. Almost no overlap was seen in the terminal distributions of the Su5 and ECu projections. Our findings demonstrate that the rat cerebellar cortex receives orofacial proprioceptive input that is processed differently from the proprioceptive signals from the other regions of the body.

  Jul. 2022, Cerebellum (London, England), 22(4) (4), 663 - 679, English, International magazine

  Scientific journal


• Uts2b is a microbiota-regulated gene expressed in vagal afferent neurons connected to enteroendocrine cells producing cholecystokinin.

  Yuta Yoshioka, Yoshihisa Tachibana, Toshihiro Uesaka, Hiroyuki Hioki, Yuya Sato, Takumi Fukumoto, Hideki Enomoto

  Enteroendocrine cells (EECs) are the primary sensory cells that sense the gut luminal environment and secret hormones to regulate organ function. Recent studies revealed that vagal afferent neurons are connected to EECs and relay sensory information from EECs to the brain stem. To date, however, the identity of vagal afferent neurons connected to a given EEC subtype and the mode of their gene responses to its intestinal hormone have remained unknown. Hypothesizing that EEC-associated vagal afferent neurons change their gene expression in response to the microbiota-related extracellular stimuli, we conducted comparative gene expression analyses of the nodose-petrosal ganglion complex (NPG) using specific pathogen-free (SPF) and germ-free (GF) mice. We report here that the Uts2b gene, which encodes a functionally unknown neuropeptide, urotensin 2B (UTS2B), is expressed in a microbiota-dependent manner in NPG neurons. In cultured NPG neurons, expression of Uts2b was induced by AR420626, the selective agonist for FFAR3. Moreover, distinct gastrointestinal hormones exerted differential effects on Uts2b expression in NPG neurons, where cholecystokinin (CCK) significantly increased its expression. The majority of Uts2b-expressing NPG neurons expressed CCK-A, the receptor for CCK, which comprised approximately 25% of all CCK-A-expressing NPG neurons. Selective fluorescent labeling of Uts2b-expressing NPG neurons revealed a direct contact of their nerve fibers to CCK-expressing EECs. This study identifies the Uts2b as a microbiota-regulated gene, demonstrates that Uts2b-expressing vagal afferent neurons transduce sensory information from CCK-expressing EECs to the brain, and suggests potential involvement of UTS2B in a modality of CCK actions.

  Jun. 2022, Biochemical and biophysical research communications, 608, 66 - 72, English, International magazine

  Scientific journal

  Link to Kobe Univ. Repository (Kernel)


• A Piezo1/KLF15/IL-6 axis mediates immobilization-induced muscle atrophy.

  Yu Hirata, Kazuhiro Nomura, Daisuke Kato, Yoshihisa Tachibana, Takahiro Niikura, Kana Uchiyama, Tetsuya Hosooka, Tomoaki Fukui, Keisuke Oe, Ryosuke Kuroda, Yuji Hara, Takahiro Adachi, Koji Shibasaki, Hiroaki Wake, Wataru Ogawa

  Whereas immobility is a common cause of muscle atrophy, the mechanism underlying this causality is unclear. We here show that KLF15 and IL-6 are up-regulated in skeletal muscle of limb-immobilized mice and that mice with KLF15 deficiency in skeletal muscle or with systemic IL-6 deficiency are protected from immobility-induced muscle atrophy. A newly developed Ca2+ bioimaging revealed that the Ca2+ concentration ([Ca2+]i) of skeletal muscle is reduced to below the basal level by immobilization, which is associated with the down-regulation of Piezo1. Acute disruption of Piezo1 in skeletal muscle induced Klf15 and Il6 expression as well as muscle atrophy, which was prevented by antibodies to IL-6. A role for the Piezo1/KLF15/IL-6 axis in immobility-induced muscle atrophy was validated by human samples. Our results thus uncover a paradigm for Ca2+ signaling in that a decrease in [Ca2+]i from the basal level triggers a defined biological event.

  Mar. 2022, The Journal of clinical investigation, 132(10) (10), 1 - 13, English, International magazine

  Scientific journal

  Link to Kobe Univ. Repository (Kernel)


• Efferent and afferent connections of supratrigeminal neurons conveying orofacial muscle proprioception in rats.

  Atsushi Yoshida, Misaki Inoue, Fumihiko Sato, Yayoi Morita, Yumi Tsutsumi, Takahiro Furuta, Katsuro Uchino, Fatema Akhter, Yong Chul Bae, Yoshihisa Tachibana, Tomio Inoue

  The supratrigeminal nucleus (Su5) is a key structure for controlling jaw movements; it receives proprioceptive sensation from jaw-closing muscle spindles (JCMSs) and sends projections to the trigeminal motor nucleus (Mo5). However, the central projections and regulation of JCMS proprioceptive sensation are not yet fully understood. Therefore, we aimed to reveal the efferent and afferent connections of the Su5 using neuronal tract tracings. Anterograde tracer injections into the Su5 revealed that the Su5 sends contralateral projections (or bilateral projections with a contralateral predominance) to the Su5, basilar pontine nuclei, pontine reticular nucleus, deep mesencephalic nucleus, superior colliculus, caudo-ventromedial edge of the ventral posteromedial thalamic nucleus, parafascicular thalamic nucleus, zona incerta, and lateral hypothalamus, and ipsilateral projections (or bilateral projections with an ipsilateral predominance) to the intertrigeminal region, trigeminal oral subnucleus, dorsal medullary reticular formation, and hypoglossal nucleus as well as the Mo5. Retrograde tracer injections into the Su5 demonstrated that the Su5 receives bilateral projections with a contralateral predominance (or contralateral projections) from the primary and secondary somatosensory cortices, granular insular cortex, and Su5, and ipsilateral projections (or bilateral projections with an ipsilateral predominance) from the dorsal peduncular cortex, bed nuclei of stria terminalis, central amygdaloid nucleus, lateral hypothalamus, parasubthalamic nucleus, trigeminal mesencephalic nucleus, parabrachial nucleus, juxtatrigeminal region, trigeminal oral and caudal subnuclei, and dorsal medullary reticular formation. These findings suggest that the Su5, which receives JCMS proprioception, has efferent and afferent connections with multiple brain regions that are involved in emotional and autonomic functions as well as orofacial motor functions.

  Jan. 2022, Brain structure & function, 227(1) (1), 111 - 129, English, International magazine

  Scientific journal


• Widespread corticopetal projections from the oval paracentral nucleus of the intralaminar thalamic nuclei conveying orofacial proprioception in rats.

  Yumi Tsutsumi, Yuka Mizuno, Tahsinul Haque, Fumihiko Sato, Takahiro Furuta, Ayaka Oka, Masayuki Moritani, Yong Chul Bae, Takashi Yamashiro, Yoshihisa Tachibana, Atsushi Yoshida

  The oval paracentral nucleus (OPC) was initially isolated from the paracentral nucleus (PC) within the intralaminar thalamic nuclei in rats. We have recently shown that the rat OPC receives proprioceptive inputs from jaw-closing muscle spindles (JCMSs). However, it remains unknown which cortical areas receive thalamic inputs from the OPC, and whether the cortical areas receiving the OPC inputs are distinct from those receiving inputs from the other intralaminar nuclei and sensory thalamic nuclei. To address this issue, we injected an anterograde tracer, biotinylated dextranamine (BDA), into the OPC, which was electrophysiologically identified by recording of proprioceptive inputs from the JCMSs. Many BDA-labeled axonal fibers and terminals from the OPC were ipsilaterally observed in the rostral and rostroventral regions of the primary somatosensory cortex (S1), the rostral region of the secondary somatosensory cortex (S2), and the most rostrocaudal levels of the granular insular cortex (GI). In contrast, a BDA injection into the caudal PC, which was located slightly rostral to the OPC, resulted in ipsilateral labeling of axonal fibers and terminals in the rostrolateral region of the medial agranular cortex and the rostromedial region of the lateral agranular cortex. Furthermore, injections of a retrograde tracer, Fluorogold, into these S1, S2, and GI regions, resulted in preferential labeling of neurons in the ipsilateral OPC among the intralaminar and sensory thalamic nuclei. These findings reveal that the rat OPC has widespread, but strong corticopetal projections, indicating that there exist divergent corticopetal pathways from the intralaminar thalamic nucleus, which process JCMS proprioceptive sensation.

  Corresponding, May 2021, Brain structure & function, 226(4) (4), 1115 - 1133, English, International magazine, Co-authored internationally

  [Refereed]

  Scientific journal


• Pain induces stable, active microcircuits in the somatosensory cortex that provide a therapeutic target.

  Takuya Okada, Daisuke Kato, Yuki Nomura, Norihiko Obata, Xiangyu Quan, Akihito Morinaga, Hajime Yano, Zhongtian Guo, Yuki Aoyama, Yoshihisa Tachibana, Andrew J Moorhouse, Osamu Matoba, Tetsuya Takiguchi, Satoshi Mizobuchi, Hiroaki Wake

  Sustained neuropathic pain from injury or inflammation remains a major burden for society. Rodent pain models have informed some cellular mechanisms increasing neuronal excitability within the spinal cord and primary somatosensory cortex (S1), but how activity patterns within these circuits change during pain remains unclear. We have applied multiphoton in vivo imaging and holographic stimulation to examine single S1 neuron activity patterns and connectivity during sustained pain. Following pain induction, there is an increase in synchronized neuronal activity and connectivity within S1, indicating the formation of pain circuits. Artificially increasing neuronal activity and synchrony using DREADDs reduced pain thresholds. The expression of N-type voltage-dependent Ca2+ channel subunits in S1 was increased after pain induction, and locally blocking these channels reduced both the synchrony and allodynia associated with inflammatory pain. Targeting these S1 pain circuits, via inhibiting N-type Ca2+ channels or other approaches, may provide ways to reduce inflammatory pain.

  Mar. 2021, Science advances, 7(12) (12), English, International magazine

  [Refereed]

  Scientific journal

  Link to Kobe Univ. Repository (Kernel)


• Proprioceptive thalamus receiving forelimb and neck muscle spindle inputs via the external cuneate nucleus in the rat.

  Yume Uemura, Tahsinul Haque, Fumihiko Sato, Yumi Tsutsumi, Haruka Ohara, Ayaka Oka, Takahiro Furuta, Yong Chul Bae, Takashi Yamashiro, Yoshihisa Tachibana, Atsushi Yoshida

  Proprioceptive signals from body muscles have historically been considered to project to the rostrodorsal shell of the ventrobasal thalamic complex [the ventral posterolateral nucleus (VPL) and ventral posteromedial nucleus (VPM)]. However, we have recently found that proprioception from rat jaw-closing muscle spindles (JCMSs) is conveyed via the supratrigeminal nucleus to the caudo-ventromedial edge of the VPM, but not to the rostrodorsal shell of the VPM. Therefore, proprioception from other body muscles may also project to thalamic regions other than the rostrodorsal shell of the VPL. We thus examined the thalamic projection from the rat external cuneate nucleus (ECu), which receives proprioceptive inputs from forelimb and neck muscles. After injection of anterograde tracer into the ECu, axon terminals were contralaterally labeled in the ventromedial part (VPLvm) of the VPL, but not in the rostrodorsal shell of the VPL. After anterograde tracer injection into the cuneate nucleus (Cu), axon terminals were widely labeled in the contralateral VPL including the VPLvm. In the VPLvm, we electrophysiologically confirmed the proprioceptive inputs responsive to electrical stimulation of the ECu or median nerve and to the pressure of forelimb/neck muscles or wrist flexion. After retrograde tracer injection into the VPLvm, neurons were contralaterally labeled in the ECu and Cu. After retrograde tracer injection into the VPL where no such proprioceptive inputs were recorded, no ECu neurons were labeled. These findings indicate that proprioception from forelimb/neck muscle spindles and JCMSs is somatotopically transmitted to the ventromedial floor of the ventrobasal thalamic complex, but not to its rostrodorsal shell.

  Corresponding, Sep. 2020, Brain structure & function, 225(7) (7), 2177 - 2192, English, International magazine, Co-authored internationally

  [Refereed]

  Scientific journal


• Ascending projection of jaw-closing muscle-proprioception to the intralaminar thalamic nuclei in rats.

  Fumihiko Sato, Seiya Kado, Yumi Tsutsumi, Yoshihisa Tachibana, Etsuko Ikenoue, Takahiro Furuta, Katsuro Uchino, Yong Chul Bae, Narikazu Uzawa, Atsushi Yoshida

  An invasive intralaminar thalamic stimulation and a non-invasive application of oral splint are both effective in treating tic symptoms of patients with Tourette syndrome (TS). Therefore, these two treatments may exert some influence on the same brain region in TS patients. We thus hypothesized that the proprioceptive input arising from the muscle spindles of jaw-closing muscles (JCMSs), known to be increased by the application of oral splint, is transmitted to the intralaminar thalamic nuclei. To test this issue, we morphologically and electrophysiologically examined the thalamic projections of proprioceptive input from the JCMSs to the intralaminar thalamic nuclei of rats. We first injected an anterograde tracer, biotinylated dextranamine, into the electrophysiologically identified supratrigeminal nucleus, which is known to receive proprioceptive inputs from the JCMSs via the trigeminal mesencephalic neurons. A moderate number of biotinylated dextranamine-labeled axon terminals were bilaterally distributed in the oval paracentral nucleus (OPC) of the intralaminar thalamic nuclei. We also detected electrophysiological responses to the electrical stimulation of bilateral masseter nerves and to sustained jaw-opening in the OPC. After injection of retrograde tracer (cholera toxin B subunit or Fluorogold) into the OPC, neuronal cell bodies were retrogradely labeled in the rostrodorsal portion of the bilateral supratrigeminal nucleus. Here, we show that proprioceptive inputs from the JCMSs are conveyed to the OPC in the intralaminar nuclei via the supratrigeminal nucleus. This study can help to understand previously unrecognized pathways of proprioception ascending inputs from the brainstem to the thalamus, which may contribute to treatments of TS patients.

  Jul. 2020, Brain research, 1739, 146830 - 146830, English, International magazine, Co-authored internationally

  [Refereed]

  Scientific journal


• Motor learning requires myelination to reduce asynchrony and spontaneity in neural activity.

  Daisuke Kato, Hiroaki Wake, Philip R Lee, Yoshihisa Tachibana, Riho Ono, Shouta Sugio, Yukio Tsuji, Yasuyo H Tanaka, Yasuhiro R Tanaka, Yoshito Masamizu, Riichiro Hira, Andrew J Moorhouse, Nobuaki Tamamaki, Kazuhiro Ikenaka, Noriyuki Matsukawa, R Douglas Fields, Junichi Nabekura, Masanori Matsuzaki

  Myelination increases the conduction velocity in long-range axons and is prerequisite for many brain functions. Impaired myelin regulation or impairment of myelin itself is frequently associated with deficits in learning and cognition in neurological and psychiatric disorders. However, it has not been revealed what perturbation of neural activity induced by myelin impairment causes learning deficits. Here, we measured neural activity in the motor cortex during motor learning in transgenic mice with a subtle impairment of their myelin. This deficit in myelin impaired motor learning, and was accompanied by a decrease in the amplitude of movement-related activity and an increase in the frequency of spontaneous activity. Thalamocortical axons showed variability in axonal conduction with a large spread in the timing of postsynaptic cortical responses. Repetitive pairing of forelimb movements with optogenetic stimulation of thalamocortical axon terminals restored motor learning. Thus, myelin regulation helps to maintain the synchrony of cortical spike-time arrivals through long-range axons, facilitating the propagation of the information required for learning. Our results revealed the pathological neuronal circuit activity with impaired myelin and suggest the possibility that pairing of noninvasive brain stimulation with relevant behaviors may ameliorate cognitive and behavioral abnormalities in diseases with impaired myelination.

  Jan. 2020, Glia, 68(1) (1), 193 - 210, English, International magazine, Co-authored internationally

  [Refereed]

  Scientific journal

  Link to Kobe Univ. Repository (Kernel)


• Dual microglia effects on blood brain barrier permeability induced by systemic inflammation.

  Koichiro Haruwaka, Ako Ikegami, Yoshihisa Tachibana, Nobuhiko Ohno, Hiroyuki Konishi, Akari Hashimoto, Mami Matsumoto, Daisuke Kato, Riho Ono, Hiroshi Kiyama, Andrew J Moorhouse, Junichi Nabekura, Hiroaki Wake

  Microglia survey brain parenchyma, responding to injury and infections. Microglia also respond to systemic disease, but the role of blood-brain barrier (BBB) integrity in this process remains unclear. Using simultaneous in vivo imaging, we demonstrated that systemic inflammation induces CCR5-dependent migration of brain resident microglia to the cerebral vasculature. Vessel-associated microglia initially maintain BBB integrity via expression of the tight-junction protein Claudin-5 and make physical contact with endothelial cells. During sustained inflammation, microglia phagocytose astrocytic end-feet and impair BBB function. Our results show microglia play a dual role in maintaining BBB integrity with implications for elucidating how systemic immune-activation impacts neural functions.

  Dec. 2019, Nature communications, 10(1) (1), 5816 - 5816, English, International magazine, Co-authored internationally

  [Refereed]

  Scientific journal

  Link to Kobe Univ. Repository (Kernel)


• Oral splint ameliorates tic symptoms in patients with tourette syndrome.

  Jumpei Murakami, Yoshihisa Tachibana, Shigehisa Akiyama, Takafumi Kato, Aya Taniguchi, Yoshiaki Nakajima, Mao Shimoda, Hiroaki Wake, Yukiko Kano, Masahiko Takada, Atsushi Nambu, Atsushi Yoshida

  Oct. 2019, Movement disorders : official journal of the Movement Disorder Society, 34(10) (10), 1577 - 1578, English, International magazine

  [Refereed]

  Link to Kobe Univ. Repository (Kernel)


• Direct and indirect pathways for choosing objects and actions.

  Hikosaka O, Kim HF, Amita H, Yasuda M, Isoda M, Tachibana Y, Yoshida A

  Mar. 2019, The European journal of neuroscience, 49(5) (5), 637 - 645, Co-authored internationally

  [Refereed]


• Microglia Enhance Synapse Activity to Promote Local Network Synchronization.

  Akiyoshi R, Wake H, Kato D, Horiuchi H, Ono R, Ikegami A, Haruwaka K, Omori T, Tachibana Y, Moorhouse AJ, Nabekura J

  Society for Neuroscience, Sep. 2018, eNeuro, 5(5) (5), ENEURO.0088 - 18.2018

  [Refereed]

  Scientific journal

  Link to Kobe Univ. Repository (Kernel)


• Transcortical descending pathways through granular insular cortex conveying orofacial proprioception

  Etsuko Ikenoue, Fatema Akhter, Yumi Tsutsumi, Fumihiko Sato, Haruka Ohara, Katsuro Uchino, Takahiro Furuta, Yoshihisa Tachibana, Atsushi Yoshida

  Elsevier B.V., May 2018, Brain Research, 1687, 11 - 19, English

  [Refereed]

  Scientific journal


• Cortical and subcortical projections from granular insular cortex receiving orofacial proprioception.

  Tsutsumi Y, Tachibana Y, Sato F, Furuta T, Ohara H, Tomita A, Fujita M, Moritani M, Yoshida A

  We have recently revealed that the proprioceptive signal from jaw-closing muscle spindles (JCMSs) is conveyed to the dorsal part of granular insular cortex rostroventrally adjacent to the rostralmost part of secondary somatosensory cortex (dGIrvs2) via the caudo-ventromedial edge (VPMcvm) of ventral posteromedial thalamic nucleus (VPM) in rats. However, it remains unclear to which cortical or subcortical structures the JCMS proprioceptive information is subsequently conveyed from the dGIrvs2. To test this issue, we injected an anterograde tracer, biotinylated dextranamine, into the electophysiologically identified dGIrvs2, and analyzed the resultant distribution profiles of labeled axon terminals in rats. Labeled terminals were distributed with an ipsilateral predominance. In the cerebral cortex, they were seen in the primary and secondary somatosensory cortices, lateral and medial agranular cortices and dorsolateral orbital cortex. In the basal ganglia, they were found in the caudate putamen, core part of accumbens nucleus, lateral globus pallidus, subthalamic nucleus, and substantia nigra pars compacta and pars reticulata. They were also observed in the central amygdaloid nucleus and extended amygdala (the interstitial nucleus of posterior limb of anterior commissure and the juxtacapsular part of lateral division of bed nucleus of stria terminalis). In the thalamus, they were seen in the reticular nucleus, ventromedial nucleus, core VPM, parvicellular part of ventral posterior nucleus, oval paracentral nucleus, medial and triangular parts of posterior nucleus, and zona incerta as well as the VPMcvm. These data suggest that the JCMS proprioceptive information through the dGIrvs2 is transmitted to the emotional 'limbic' regions as well as sensorimotor regions.

  2018, Neuroscience, 388, 317 - 329, English, International magazine

  [Refereed]

  Scientific journal


• THALAMO-INSULAR PATHWAY CONVEYING OROFACIAL MUSCLE PROPRIOCEPTION IN THE RAT

  Fumihiko Sato, Yume Uemura, Chiharu Kanno, Yumi Tsutsumi, Akiko Tomita, Ayaka Oka, Takafumi Kato, Katsuro Uchino, Jumpei Murakami, Tahsinul Haque, Yoshihisa Tachibana, Atsushi Yoshida

  Dec. 2017, NEUROSCIENCE, 365, 158 - 178, English

  [Refereed]

  Scientific journal


• Information processing from the motor cortices to the subthalamic nucleus and globus pallidus and their somatotopic organizations revealed electrophysiologically in monkeys

  Hirokazu Iwamuro, Yoshihisa Tachibana, Yoshikazu Ugawa, Nobuhito Saito, Atsushi Nambu

  Dec. 2017, EUROPEAN JOURNAL OF NEUROSCIENCE, 46(11) (11), 2684 - 2701, English

  [Refereed]

  Scientific journal

  Link to Kobe Univ. Repository (Kernel)


• Orofacial proprioceptive thalamus of the rat

  Atsushi Yoshida, Takashi Fujio, Fumihiko Sato, Md Sams Sazzad Ali, Tahsinul Haque, Haruka Ohara, Masayuki Moritani, Takafumi Kato, Jonathan O. Dostrovsky, Yoshihisa Tachibana

  Last, Aug. 2017, BRAIN STRUCTURE & FUNCTION, 222(6) (6), 2655 - 2669, English

  [Refereed]

  Scientific journal


• Flavour-enhanced cortisol release during gum chewing

  Yoko Hasegawa, Yoshihisa Tachibana, Takahiro Ono, Hiromitsu Kishimoto

  Apr. 2017, PLOS ONE, 12(4) (4), e0173475, English

  [Refereed]

  Scientific journal

  Link to Kobe Univ. Repository (Kernel)


• Computational Model of Recurrent Subthalamo-Pallidal Circuit for Generation of Parkinsonian Oscillations

  Osamu Shouno, Yoshihisa Tachibana, Atsushi Nambu, Kenji Doya

  Mar. 2017, FRONTIERS IN NEUROANATOMY, 11, 21, English

  [Refereed]

  Scientific journal

  Link to Kobe Univ. Repository (Kernel)


• REVISITING THE SUPRATRIGEMINAL NUCLEUS IN THE RAT

  T. Fujio, F. Sato, Y. Tachibana, T. Kato, A. Tomita, K. Higashiyama, T. Ono, Y. Maeda, A. Yoshida

  Jun. 2016, NEUROSCIENCE, 324, 307 - 320, English

  [Refereed]

  Scientific journal


• Direct projection from the lateral habenula to the trigeminal mesencephalic nucleus in rats

  Haruka Ohara, Yoshihisa Tachibana, Takashi Fujio, Rieko Takeda-Ikeda, Fumihiko Sato, Ayaka Oka, Takafumi Kato, Etsuko Ikenoue, Takashi Yamashiro, Atsushi Yoshida

  Jan. 2016, BRAIN RESEARCH, 1630, 183 - 197, English

  [Refereed]

  Scientific journal


• Mechanism of parkinsonian neuronal oscillations in the primate basal ganglia: Some considerations based on our recent work

  Atsushi Nambu, Yoshihisa Tachibana

  Frontiers Research Foundation, May 2014, Frontiers in Systems Neuroscience, 8(MAY) (MAY), English

  [Refereed]

  Scientific journal


• Flavor-Enhanced Modulation of Cerebral Blood Flow during Gum Chewing

  Yoko Hasegawa, Yoshihisa Tachibana, Joe Sakagami, Min Zhang, Masahiro Urade, Takahiro Ono

  6, Jun. 2013, PLoS ONE, 8(6) (6), English

  [Refereed]

  Scientific journal


• The Primate Ventral Pallidum Encodes Expected Reward Value and Regulates Motor Action

  Yoshihisa Tachibana, Okihide Hikosaka

  Nov. 2012, NEURON, 76(4) (4), 826 - 837, English

  [Refereed]

  Scientific journal


• Reply: Cortically evoked responses of human pallidal neurons

  Hiroki Nishibayashi, Atsuhi Nambu, Yoshihisa Tachibana, Toru Itakura

  Dec. 2011, Movement Disorders, 26(14) (14), 2583 - 2584, English

  [Refereed]

  Scientific journal


• Reduced pallidal output causes dystonia

  Atsushi Nambu, Satomi Chiken, Pullanipally Shashidharan, Hiroki Nishibayashi, Mitsuhiro Ogura, Koji Kakishita, Satoshi Tanaka, Yoshihisa Tachibana, Hitoshi Kita, Toru Itakura

  Nov. 2011, Frontiers in Systems Neuroscience, 5(2011) (2011), 89, English

  [Refereed]

  Scientific journal


• Subthalamo-pallidal interactions underlying parkinsonian neuronal oscillations in the primate basal ganglia

  Yoshihisa Tachibana, Hirokazu Iwamuro, Hitoshi Kita, Masahiko Takada, Atsushi Nambu

  Nov. 2011, EUROPEAN JOURNAL OF NEUROSCIENCE, 34(9) (9), 1470 - 1484, English

  [Refereed]

  Scientific journal


• Cortically Evoked Responses of Human Pallidal Neurons Recorded During Stereotactic Neurosurgery

  Hiroki Nishibayashi, Mitsuhiro Ogura, Koji Kakishita, Satoshi Tanaka, Yoshihisa Tachibana, Atsushi Nambu, Hitoshi Kita, Toru Itakura

  Feb. 2011, MOVEMENT DISORDERS, 26(3) (3), 469 - 476, English

  [Refereed]

  Scientific journal


• Organization of motor cortical inputs in the globus pallidus via the subthalamic nucleus in monkeys

  Iwamuro Hirokazu, Tachibana Yoshihisa, Saito Nobuhito, Nambu Atsushi

  2008, NEUROSCIENCE RESEARCH, 61, S241

  [Refereed]


• Motor cortical control of internal pallidal activity through glutamatergic and GABAergic inputs in awake monkeys

  Yoshihisa Tachibana, Hitoshi Kita, Satomi Chiken, Masahiko Takada, Atsushi Nambu

  Jan. 2008, EUROPEAN JOURNAL OF NEUROSCIENCE, 27(1) (1), 238 - 253, English

  [Refereed]

  Scientific journal


• Abnormal oscillatory discharges of basal ganglia neurons in parkinsonian monkeys

  Tachibana Yoshihisa, Iwamuro Hirokazu, Takada Masahiko, Nambu Atsushi

  2007, NEUROSCIENCE RESEARCH, 58, S60

  [Refereed]


• Serotonin modulates pallidal neuronal activity in the awake monkey

  Hitoshi Kita, Satomi Chiken, Yoshihisa Tachibana, Atsushi Nambu

  Jan. 2007, JOURNAL OF NEUROSCIENCE, 27(1) (1), 75 - 83, English

  [Refereed]

  Scientific journal


• Origins of GABA(A) and GABA(B) receptor-mediated responses of globus pallidus induced after stimulation of the putamen in the monkey

  H Kita, S Chiken, Y Tachibana, A Nambu

  Jun. 2006, JOURNAL OF NEUROSCIENCE, 26(24) (24), 6554 - 6562, English

  [Refereed]

  Scientific journal


• Ionotropic glutamate receptor antagonism can reduce abnormal pallidal discharges in parkinsonian monkeys

  Tachibana Yoshihisa, Iwamuro Hirokazu, Takada Masahiko, Nambu Atsushi

  2006, NEUROSCIENCE RESEARCH, 55, S200

  [Refereed]


• Down-regulation of metabotropic glutamate receptor 1 alpha in globus pallidus and substantia nigra of parkinsonian monkeys

  K Kaneda, Y Tachibana, M Imanishi, H Kita, R Shigemoto, A Nambu, M Takada

  Dec. 2005, EUROPEAN JOURNAL OF NEUROSCIENCE, 22(12) (12), 3241 - 3254, English

  [Refereed]

  Scientific journal


• Balance of monosynaptic excitatory and disynaptic inhibitory responses of the globus pallidus induced after stimulation of the subthalamic nucleus in the monkey

  H Kita, Y Tachibana, A Nambu, S Chiken

  Sep. 2005, JOURNAL OF NEUROSCIENCE, 25(38) (38), 8611 - 8619, English

  [Refereed]

  Scientific journal


• Different corticostriatal projections from two parts of the cortical masticatory area in the rabbit

  Y Masuda, SK Kim, T Kato, S Iida, A Yoshida, Y Tachibana, T Morimoto

  Mar. 2005, EXPERIMENTAL BRAIN RESEARCH, 161(3) (3), 397 - 404, English

  [Refereed]

  Scientific journal


• Role of ionotropic glutamatergic and GABAergic inputs on the firing activity of neurons in the external pallidum in awake monkeys

  H Kita, A Nambu, K Kaneda, Y Tachibana, M Takada

  Nov. 2004, JOURNAL OF NEUROPHYSIOLOGY, 92(5) (5), 3069 - 3084, English

  [Refereed]

  Scientific journal


• Organization of prefrontal outflow toward frontal motor-related areas in macaque monkeys

  M Takada, A Nambu, N Hatanaka, Y Tachibana, S Miyachi, M Taira, M Inase

  Jun. 2004, EUROPEAN JOURNAL OF NEUROSCIENCE, 19(12) (12), 3328 - 3342, English

  [Refereed]

  Scientific journal


• Input-output organization of the rostral part of the dorsal premotor cortex, with special reference to its corticostriatal projection

  Y Tachibana, A Nambu, N Hatanaka, S Miyachi, M Takada

  Jan. 2004, NEUROSCIENCE RESEARCH, 48(1) (1), 45 - 57, English

  [Refereed]

  Scientific journal


• Influence of oro-facial sensory input on the output of the cortical masticatory area in the anesthetized rabbit

  Yuji Masuda, Yoshihisa Tachibana, Tomio Inoue, Koichi Iwata, Toshifumi Morimoto

  2002, Experimental Brain Research, 146(4) (4), 501 - 510, English

  [Refereed]

  Scientific journal


• Alteration of medullary dorsal horn neuronal activity following inferior alveolar nerve transection in rats

  K Iwata, T Imai, Y Tsuboi, A Tashiro, A Ogawa, T Morimoto, Y Masuda, Y Tachibana, J Hu

  Dec. 2001, JOURNAL OF NEUROPHYSIOLOGY, 86(6) (6), 2868 - 2877, English

  [Refereed]

  Scientific journal

• 閉口筋筋紡錘感覚の小脳皮質への投射

  堤友美, 佐藤文彦, 古田貴寛, 孫在隣, 加藤隆史, 橘吉寿, 吉田篤, 吉田篤

  2023, Journal of Oral Biosciences Supplement (Web), 2023


• 味および香りがガム咀嚼時のストレスに及ぼす影響

  長谷川 陽子, 橘 吉寿, 小野 高裕

  (NPO)日本咀嚼学会, Nov. 2012, 日本咀嚼学会雑誌, 22(2) (2), 144 - 145, Japanese

• Roles of aquaporin9 in diabetic retinal neurodegeneration

  楠原 仙太郎, 淺原 俊一郎, 橘 吉寿

  Japan Society for the Promotion of Science, Grants-in-Aid for Scientific Research, Grant-in-Aid for Scientific Research (C), Kobe University, 01 Apr. 2021 - 31 Mar. 2024

  1.研究内容:遺伝子改変糖尿病マウスを安定的に得るためにInsCre;Pdkflox/+マウスとPdkflox/floxマウスを用いた体外受精を行い凍結受精卵を作成した。このことによって、任意の時期にInsCre;Pdkflox/flox（糖尿病マウス）およびPdkflox/floxマウス（コントロールマウス）を得ることができるようになった。遺伝子改変マウスCx3cr1-GFPマウス（ミクログリア標識）およびアデノ随伴ウイルス（アストロサイト、網膜神経節細胞）による標識を適宜利用し、糖尿病マウスでの２光子顕微鏡による生体イメージングを行った。ミクログリアの動きおよび形態変化を定量化する方法につき複数のアルゴリズムをトライし、安定して評価できる系が確立されつつある。また、AQP9の糖尿病網膜神経変性における役割の解明を進めるために、InsCre;Pdkflox/flox;Aqp9-/-マウスおよびPdkflox/flox;Aqp9+/-マウス（コントロール）の安定供給に向けマウスの交配を続けていると同時にAqp9-/-マウスにストレプトゾトシンを投与し高血糖を誘発して解析を進めている。 2.研究の意義:多面的な神経保護作用を有する乳酸のトランスポーターであるAQP9は糖尿病早期における糖尿病網膜神経変性に関与している可能性が高い。慢性炎症の際に早期から異常が認められるミクログリアの変化が２光子顕微鏡による生体イメージングで解析できていることから、この研究を続けることによって糖尿病網膜におけるAQP9の役割が明らかになるものと思われる。 3. 研究の重要性:本研究によって糖尿病早期におけるAQP9の役割が明らかになれば、乳酸をターゲットにした糖尿病網膜症への早期介入への道筋が示されることになり将来の失明予防に大いに貢献できると考える。


• 神経回路可視化と光操作による薬物依存形成脳内機構の解明

  橘 吉寿, 金田 勝幸

  日本学術振興会, 科学研究費助成事業, 基盤研究(B), 神戸大学, 01 Apr. 2021 - 31 Mar. 2024


• Structure of behavior: comparative cognitive neurobiological approach

  Toda Koji

  Japan Society for the Promotion of Science, Grants-in-Aid for Scientific Research, Fund for the Promotion of Joint International Research (Fostering Joint International Research (B)), 09 Oct. 2018 - 31 Mar. 2021

  In this project, we aimed to understand psychological and neurobiological mechanisms of the behavior. We established novel behavioral experiments including appetitive and aversive classical/operant conditioning tasks for head-fixed mice. Using these tasks, we measured and manipulated neuronal activities with genetical, histological, pharmacological, optogenetic, and chemogenetic approaches. We also applied computational approach to understand the mechanism of the behavior.


• Roles of neurovascular unit in diabetic retinal neurodegeneration

  Kusuhara Sentaro

  Japan Society for the Promotion of Science, Grants-in-Aid for Scientific Research, Grant-in-Aid for Scientific Research (C), Kobe University, 01 Apr. 2018 - 31 Mar. 2021

  We evaluated the damage to neurovascular unit and performed in vivo two-photon imaging of retinal glial cells in diabetic (InsCreTg; Pdk1flox/flox) mice. Immunohistochemistry disclosed that microglial activation as well as decrease in laminin thickness and ganglion cell axons proceed other cellular and extracellular matrix events in diabetic mouse retinas. Improvement of optical system including contact lens enabled high-resolution in vivo retinal imaging. Using this imaging system, we observed microglia migrating around retinal vessels and astrocytes with its processes extending towards them and detected leukocytes slowly moving in the retinal vessel lumen.


• Neural mechanism of tic disorders revealed by optical imaging in the brain

  Tachibana Yoshihisa

  Japan Society for the Promotion of Science, Grants-in-Aid for Scientific Research, Grant-in-Aid for Scientific Research (C), Kobe University, 01 Apr. 2018 - 31 Mar. 2021

  The pathophysiology of motor and vocal tics remains unknown. Recently, the disinhibition of the striatum is suggested to cause the tic symptoms. To test this issue, we unilaterally injected GABA antagonist bicuculline into the mouse striatum. We found that the local bicuculline into the striatum induced contralateral muscle twitches depending on injection sites. Then, we investigated the activated brain regions by striatal disinhibition using c-Fos immunohistochemistry. We found that limbic structures such as the amygdala, cingulate cortex, insular cortex as well as the primary motor cortex were activated although the structure does not receive direct inputs from the striatum. These data suggest that the tic is generated by abnormal neuronal processing in the motor-limbic network in the brain.


• 発振現象を基軸としたパーキンソン病の病態解明とオプトDBS開発

  橘 吉寿

  日本学術振興会, 科学研究費助成事業, 新学術領域研究(研究領域提案型), 神戸大学, 01 Apr. 2018 - 31 Mar. 2020

  パーキンソン病において、大脳基底核内の局所回路における異常リズム形成がパーキンソン病症状発現に深く関与するという報告がこれまでなされている。また、この異常リズムを是正する目的での視床下核もしくは淡蒼球内節（ともに大脳基底核の構成要素である）の高頻度電気刺激が、パーキンソン病症状を改善することが臨床的に知られている。しかしながら、パーキンソン病患者ならびにパーキンソン病モデル動物において、大脳基底核で異常発振が見られるものの、大脳皮質―大脳基底核―視床ループの一部である大脳皮質運動野において異常発振が起こるかどうか未だ明らかでない。これらの問題を解決するため、パーキンソン病モデルマウスにおいて、大脳基底核と密に連絡し最終的な運動出力を担う大脳皮質運動野で基底核と同様の異常リズムが観察されるかどうかを2光子顕微鏡イメージングにて検証した。その結果、パーキンソン病症状発現前に比べ、症状発現後において、大脳皮質一次運動野の同期発火は、大脳皮質浅層（II/III層）で有意に増加し、大脳皮質深層（V層）では有意な増加を示さないことが明らかとなった。また、大脳皮質一次運動野のII/III層は線条体に、V層は視床下核にそれぞれ投射することが解剖学的に確認されたので、ウイルスの二重感染により線条体もしくは視床下核にそれぞれ投射する大脳皮質運動野神経細胞を可視化することに成功し、さらに投射特異的な光遺伝学による人工神経活動操作法も確立したので、今後は、細胞種特異的に大脳皮質神経細胞の異常な同期化を是正することで、パーキンソン病症状が改善するかについて検証したい。


• Study on brain mechanisms involved in orofacial functions to map the entire brain connectivity (connectome)

  Yoshida Atsushi

  Japan Society for the Promotion of Science, Grants-in-Aid for Scientific Research, Grant-in-Aid for Challenging Exploratory Research, Osaka University, 01 Apr. 2016 - 31 Mar. 2018

  We had the following results in rats. (1) The proprioception from masticatory muscle spindles (MMS-proprioception) was conveyed to the supratrigeminal nucleus (Su5), then to the caudo-ventromedial edge of ventral posteromedial thalamic nucleus (VPMcvm), and finally to the dorsal part of granular insular cortex (dGIrvs2), but not to the primary and secondary somatosensory cortices (S1 and S2). The MMS-proprioception may make effects on emotion and homeostasis through this pathway, but not on the sensory discrimination. (2) The other orofacial sensations were conveyed to the trigeminal sensory nuclear complex, and then to the core VPM, and finally to the S1 and S2. (3) These two corticopetal pathways did not overlap each other. This study has for the first time revealed functional significances of muscle proprioception, and, thus, will contribute very much to the study of connectome in brain science.


• The effect that the taste/odor of the chewing food gives for a stress reaction

  Hasegawa Yoko, ONO Takahiro, TACHIBANA Yoshihisa

  Japan Society for the Promotion of Science, Grants-in-Aid for Scientific Research, Grant-in-Aid for Scientific Research (C), Hyogo Medical University, 01 Apr. 2013 - 31 Mar. 2016

  This study is aimed to clarify the relationship between taste/odor and stress response of food chewing. The study divided into three purpose; (1)Examine the taste/odor of chewing foods that cause stress, (2)To evaluate regarding higher brain functions and changes in the deliciousness of food, (3)The influence of the autonomic nervous regulation by differences in preferences for chewing food． As a result, subjects could discriminate between the types of gum without prior information. Saliva cortisol concentrations were highest and lowest for the subjects who chewed the most flavourful gum and the least flavourful gum, respectively. In additon, no significant correlation was found between performances of the mental arithmetic test and subjective sensory evaluation, except for a weak negative correlation with taste. More examination will be necessary in future.


• ハイリスク・ハイリターン、ローリスク・ローリターンを選択する神経基盤と調節因子

  橘 吉寿

  日本学術振興会, 科学研究費助成事業, 新学術領域研究(研究領域提案型), 生理学研究所, 01 Apr. 2012 - 31 Mar. 2014

  本研究課題においては、（サル）がローリスク・ローリターン、ハイリスク・ハイリターンな状況におかれた際、どのような行動選択（意思決定）を行い、その際、大脳基底核にある視床下核ニューロンがどのように活動するかを電気生理学的に記録・解析することを目標とする。申請者が用いる行動課題（眼球運動課題）においては、視覚刺激の色情報に基づいた意思決定をサルは行わねばならない。具体的には、まず中央に四角形が現れ、サルが一定期間固視したあと、左右に二つの視覚刺激が呈示される。一つは緑色の視覚刺激で、研究期間を通して、ローリスク・ローリターンな報酬を予測させる刺激である。もう一つの刺激は、赤色の視覚刺激で、これは絶えずハイリスク・ハイリターンな報酬を予測させる刺激である。遅延期間のあと、固視点が消灯し、それを合図にサルは、左右のいずれかの視覚刺激に急速眼球運動を行わねばならない。ローリスク・ローリターンを示す緑色の刺激を選択した場合、例えば、ある決まった量の報酬を5回に4回の割合で得ることが出来る。一方、ハイリスク・ハイリターンを示す赤色の刺激を選んだ場合は、例えば、5回に1回の割合でしか報酬を得ることが出来ない。ただし、報酬を得ることが出来る試行においては、報酬量が緑色の刺激を選んだ際に得られる報酬量の4倍となる。このような眼球運動課題をサルに課した結果、ハイリスク・ハイリターンを示す刺激に対し、ローリスク・ローリターンとなる刺激をサルは好んで選択した。齧歯類は総じてハイリスク・ハイリターンとなる刺激を好むのに対し、サルはヒトと同様に、ローリスク・ローリターンを好んで選んだことは非常に興味深い結果と考えられる。また、その際に視床下核ニューロンから非常にユニークな関連神経活動が記録された。


• Neural mechanism for stabilizing our behavior -novel function of the basal ganglia-

  TACHIBANA Yoshihisa

  Japan Society for the Promotion of Science, Grants-in-Aid for Scientific Research, Grant-in-Aid for Young Scientists (B), National Institute for Physiological Sciences, 01 Apr. 2012 - 31 Mar. 2014

  The basal ganglia are considered to have two functions in motor control: an accelerating system and a braking system. In particular, the subthalamic nucleus (STN) is believed to be part of the braking system. Based on the traditional concept, I hypothesized that the STN increased its neuronal activity when the animal's motor action was suppressed (e.g., longer reaction time and slower velocity). However, the result from my recoding of STN activity in behaving monkeys was different from the prediction; the STN activity was increased when the motor action was facilitated. The previous study also showed that the neuronal activity in the striatum (part of the accelerating system in the basal ganglia) was increased when the action was facilitated. These data indicate that the accelerating and braking systems in the basal ganglia may work synergistically to stabilize motor actions.


• 脳深部刺激療法がパーキンソン病を改善する神経生理学的基盤を探る

  橘 吉寿

  日本学術振興会, 科学研究費助成事業, 若手研究(B), 生理学研究所, 2007 - 2008

  パーキンソン病の病態生理を解明するために、MPTP神経毒誘発性パーキンソン病モデルサルを作製し、大脳基底核の神経活動を記録した。その結果、淡蒼球外節、淡蒼球内節ならびに視床下核において、過度のbeta帯域(13-17Hz)の発振現象を示す神経活動が多数観察された。これらの異常な神経活動はMPTP神経毒投与前においては認められなかったことから、この大脳基底核ニューロンにおけるbeta帯域の発振現象がパーキンソン症状を惹起している可能性が考えられる。モデル動物へのパーキンソン病治療薬であるL-DOPAの投与により、パーキンソン症状の消失と共に、beta帯域の異常発振は減弱した。つぎに、大脳基底核の出力核である淡蒼球内節の異常発振は、視床下核からのグルタミン酸作動性入力により惹起されるものであるという仮説のもと、視床下核にムシモールを注入し視床下核の神経活動を不活化したところ、パーキンソン症状の減弱と共に、淡蒼球内節の発振現象は消失した。また、視床下核の発振現象についてさらに詳細に調べたところ、淡蒼球外節からのGABA作動性入力と大脳皮質からのグルタミン酸作動性入力により視床下核の発振活動が増強されることが明らかとなった。本研究は、パーキンソン病患者に対して視床下核あるいは淡蒼球内節の脳深部刺激療法が奏功する作用メカニズムを考える上で、非常に重要な神経生理学的知見を与えるものであると考えられる。


• Dynamic functions of cortico-basal ganglia loop

  NAMBU Atsushi, HATANAKA Nobuhiko, TACHIBANA Yoshihisa, CHIKEN Satomi

  Japan Society for the Promotion of Science, Grants-in-Aid for Scientific Research, Grant-in-Aid for Scientific Research (B), National Institute for Physiological Sciences, 2006 - 2008

  (1)正常な大脳基底核の機能に関する研究 線条体、淡蒼球外節・内節の活動を、覚醒下、課題遂行中のサルから記録し、大脳皮質刺激に対する応答や運動との相関を調べた。また、局所に薬剤を注入することにより、これらの神経活動が引き起こされるメカニズムについて検討した。 (2)大脳基底核疾患の病態に関する研究 MPTPを投与して作製したパーキンソン病モデルサルや、ヒト全身性ジストニアの原因遺伝子であるDYT1遺伝子を組み込んだジストニアモデルマウス、さらにはステレオ手術時に大脳基底核疾患患者などから大脳基底核の神経活動を記録することにより、これら大脳基底核疾患の病態について検討した。 その結果、ハイパー直接路・直接路・間接路が順にダイナミックに働くことにより、不必要な運動が抑制され、必要な運動のみが正確なタイミングで引き起こされるというモデルが妥当であり、これによってある程度、大脳基底核疾患の病態を説明できることが示された。