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Last Updated :2024/07/25
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Profile and Settings
Name (Japanese)
KarubeName (Kana)
FuyukiName
200901015142296816
通称等の別名
- Hokkaido University
Achievement
Research Interests
Research Areas
Education
- 1993/04 - 1998/03 東京大学大学院
- 1989/04 - 1993/03 Tokyo University of Agriculture and Technology Faculty of Agriculture
Published Papers
- Takahide Kadosaka, Masaya Watanabe, Hiroyuki Natsui, Takuya Koizumi, Motoki Nakao, Taro Koya, Hikaru Hagiwara, Rui Kamada, Taro Temma, Fuyuki Karube, Fumino Fujiyama, Toshihisa AnzaiAmerican journal of physiology. Heart and circulatory physiology 324 (3) H341-H354 2023/01/06Diabetic cardiomyopathy has been reported to increase the risk of fatal ventricular arrhythmia. The beneficial effects of the selective sodium-glucose co-transporter 2 inhibitor have not been fully examined in the context of anti-arrhythmic therapy, especially its direct cardioprotective effects despite the negligible SGLT2 expression in cardiomyocytes. We aimed to examine the anti-arrhythmic effects of empagliflozin (EMPA) treatment on diabetic cardiomyocytes, with a special focus on Ca2+ handling. We conducted echocardiography and hemodynamic studies and studied electrophysiology, Ca2+ handling, and protein expression in C57BLKS/J-leprdb/db mice (db/db mice) and their non-diabetic lean heterozygous Leprdb/+ littermates (db/+ mice). Preserved systolic function with diastolic dysfunction was observed in 16-week-old db/db mice. During arrhythmia induction, db/db mice had significantly increased premature ventricular complexes (PVCs) than controls, which was attenuated by EMPA. In protein expression analyses, calmodulin-dependent protein kinase II (CaMKII) Thr287 autophosphorylation and CaMKII-dependent RyR2 phosphorylation (S2814) were significantly increased in diabetic hearts, which were inhibited by EMPA. Additionally, global O-GlcNAcylation significantly decreased with EMPA treatment. Furthermore, EMPA significantly inhibited ventricular cardiomyocyte glucose uptake. Diabetic cardiomyocytes exhibited increased spontaneous Ca2+ events and decreased sarcoplasmic reticulum (SR) Ca2+ content, along with impaired Ca2+ transient, all of which normalized with EMPA treatment. Notably, most EMPA-induced improvements in Ca2+ handling were abolished by the addition of an O-GlcNAcase (OGA) inhibitor. In conclusion, EMPA attenuated ventricular arrhythmia inducibility by normalizing the intracellular Ca2+ handling, and we speculated that this effect was, at least partly, due to the inhibition of O-GlcNAcylation via the suppression of glucose uptake into cardiomyocytes.
- Kumiko Ogata, Fuko Kadono, Yasuharu Hirai, Ken-ichi Inoue, Masahiko Takada, Fuyuki Karube, Fumino FujiyamaFrontiers in Neuroanatomy 16 2022/02/04 [Refereed][Not invited]
The striatum is one of the key nuclei for adequate control of voluntary behaviors and reinforcement learning. Two striatal projection neuron types, expressing either dopamine receptor D1 (D1R) or dopamine receptor D2 (D2R) constitute two independent output routes: the direct or indirect pathways, respectively. These pathways co-work in balance to achieve coordinated behavior. Two projection neuron types are equivalently intermingled in most striatal space. However, recent studies revealed two atypical zones in the caudal striatum: the zone in which D1R-neurons are the minor population (D1R-poor zone) and that in which D2R-neurons are the minority (D2R-poor zone). It remains obscure as to whether these imbalanced zones have similar properties on axonal projections and electrophysiology compared to other striatal regions. Based on morphological experiments in mice using immunofluorescence, in situ hybridization, and neural tracing, here, we revealed that the poor zones densely projected to the globus pallidus and substantia nigra pars lateralis, with a few collaterals in substantia nigra pars reticulata and compacta. Similar to that in other striatal regions, D1R-neurons were the direct pathway neurons. We also showed that the membrane properties of projection neurons in the poor zones were largely similar to those in the conventional striatum using in vitro electrophysiological recording. In addition, the poor zones existed irrespective of the age or sex of mice. We also identified the poor zones in the common marmoset as well as other rodents. These results suggest that the poor zones in the caudal striatum follow the conventional projection patterns irrespective of the imbalanced distribution of projection neurons. The poor zones could be an innate structure and common in mammals. The unique striatal zones possessing highly restricted projections could relate to functions different from those of motor-related striatum. - Shogo Soma, Naofumi Suematsu, Akinori Y Sato, Keisuke Tsunoda, Allen Bramian, Anish Reddy, Koki Takabatake, Fuyuki Karube, Fumino Fujiyama, Satoshi ShimegiNeurobiology of Learning and Memory 183 107484 - 107484 1074-7427 2021/09 [Refereed][Not invited]
- Moritoshi Hirono, Fuyuki Karube, Yuchio YanagawaFrontiers in Neural Circuits 15 2021/06/14 [Refereed][Not invited]
Classically, the cerebellum has been thought to play a significant role in motor coordination. However, a growing body of evidence for novel neural connections between the cerebellum and various brain regions indicates that the cerebellum also contributes to other brain functions implicated in reward, language, and social behavior. Cerebellar Purkinje cells (PCs) make inhibitory GABAergic synapses with their target neurons: other PCs and Lugaro/globular cells via PC axon collaterals, and neurons in the deep cerebellar nuclei (DCN) via PC primary axons. PC-Lugaro/globular cell connections form a cerebellar cortical microcircuit, which is driven by serotonin and noradrenaline. PCs’ primary outputs control not only firing but also synaptic plasticity of DCN neurons following the integration of excitatory and inhibitory inputs in the cerebellar cortex. Thus, strong PC-mediated inhibition is involved in cerebellar functions as a key regulator of cerebellar neural networks. In this review, we focus on physiological characteristics of GABAergic transmission from PCs. First, we introduce monoaminergic modulation of GABAergic transmission at synapses of PC-Lugaro/globular cell as well as PC-large glutamatergic DCN neuron, and a Lugaro/globular cell-incorporated microcircuit. Second, we review the physiological roles of perineuronal nets (PNNs), which are organized components of the extracellular matrix and enwrap the cell bodies and proximal processes, in GABA release from PCs to large glutamatergic DCN neurons and in cerebellar motor learning. Recent evidence suggests that alterations in PNN density in the DCN can regulate cerebellar functions. - Fuyuki Karube, Susumu Takahashi, Kenta Kobayashi, Fumino FujiyamaeLife 8 (e49511) 2019/11/12 [Refereed][Not invited]
The basal ganglia are critical for the control of motor behaviors and for reinforcement learning. Here, we demonstrate in rats that primary and secondary motor areas (M1 and M2) make functional synaptic connections in the globus pallidus (GP), not usually thought of as an input site of the basal ganglia. Morphological observation revealed that the density of axonal boutons from motor cortices in the GP was 47% and 78% of that in the subthalamic nucleus (STN) from M1 and M2, respectively. Cortical excitation of GP neurons was comparable to that of STN neurons in slice preparations. FoxP2-expressing arkypallidal neurons were preferentially innervated by the motor cortex. The connection probability of cortico-pallidal innervation was higher for M2 than M1. These results suggest that cortico-pallidal innervation is an additional excitatory input to the basal ganglia, and that it can affect behaviors via the cortex-basal ganglia-thalamus motor loop. - Fujiyama F, Unzai T, KARUBE FNeurochemistry International 125 67 - 73 2019/01 [Refereed][Not invited]
- Hashimotodani Y, Karube F, Yanagawa Y, Fujiyama F, Kano MCell Reports 25 2704 - 2715 2018/11 [Refereed][Not invited]
- Yasutake Nakano, Fuyuki Karube, Yasuharu Hirai, Kenta Kobayashi, Hiroyuki Hioki, Shinichiro Okamoto, Hiroshi Kameda, Fumino FujiyamaJournal of neuroscience research 96 (7) 1186 - 1207 0360-4012 2018/07 [Refereed][Not invited]
In rodents, the dorsolateral striatum regulates voluntary movement by integrating excitatory inputs from the motor-related cerebral cortex and thalamus to produce contingent inhibitory output to other basal ganglia nuclei. Striatal parvalbumin (PV)-producing interneurons receiving this excitatory input then inhibit medium spiny neurons (MSNs) and modify their outputs. To understand basal ganglia function in motor control, it is important to reveal the precise synaptic organization of motor-related cortical and thalamic inputs to striatal PV interneurons. To examine which domains of the PV neurons receive these excitatory inputs, we used male bacterial artificial chromosome transgenic mice expressing somatodendritic membrane-targeted green fluorescent protein in PV neurons. An anterograde tracing study with the adeno-associated virus vector combined with immunodetection of pre- and postsynaptic markers visualized the distribution of the excitatory appositions on PV dendrites. Statistical analysis revealed that the density of thalamostriatal appositions along the dendrites was significantly higher on the proximal than distal dendrites. In contrast, there was no positional preference in the density of appositions from axons of the dorsofrontal cortex. Population observations of thalamostriatal and corticostriatal appositions by immunohistochemistry for pathway-specific vesicular glutamate transporters confirmed that thalamic inputs preferentially, and cortical ones less preferentially, made apposition on proximal dendrites of PV neurons. This axodendritic organization suggests that PV neurons produce fast and reliable inhibition of MSNs in response to thalamic inputs and process excitatory inputs from motor cortices locally and plastically, possibly together with other GABAergic and dopaminergic dendritic inputs, to modulate MSN inhibition. - Hirono M, Watanabe S, Karube F, Fujiyama F, Kawahara S, Nagao S, Yanagawa Y, Misonou HThe Journal of neuroscience : the official journal of the Society for Neuroscience 38 (27) 6130 - 6144 0270-6474 2018/07 [Refereed][Not invited]
- Yoon-Mi Oh, Fuyuki Karube, Susumu Takahashi, Kenta Kobayashi, Masahiko Takada, Motokazu Uchigashima, Masahiko Watanabe, Kayo Nishizawa, Kazuto Kobayashi, Fumino FujiyamaBRAIN STRUCTURE & FUNCTION 222 (5) 2359 - 2378 1863-2653 2017/12 [Refereed][Not invited]
In the present study, we generated a novel parvalbumin (PV)-Cre rat model and conducted detailed morphological and electrophysiological investigations of axons from PV neurons in globus pallidus (GP). The GP is considered as a relay nucleus in the indirect pathway of the basal ganglia (BG). Previous studies have used molecular profiling and projection patterns to demonstrate cellular heterogeneity in the GP; for example, PV-expressing neurons are known to comprise approximately 50% of GP neurons and represent majority of prototypic neurons that project to the subthalamic nucleus and/or output nuclei of BG, entopeduncular nucleus and substantia nigra (SN). The present study aimed to identify the characteristic projection patterns of PV neurons in the GP (PV-GP neurons) and determine whether these neurons target dopaminergic or GABAergic neurons in SN pars compacta (SNc) or reticulata (SNr), respectively. We initially found that (1) 57% of PV neurons co-expressed Lim-homeobox 6, (2) the PVGP terminals were preferentially distributed in the ventral part of dorsal tier of SNc, (3) PV-GP neurons formed basket-like appositions with the somata of tyrosine hydroxylase, PV, calretinin and cholecystokinin immunoreactive neurons in the SN, and (4) in vitro wholecell recording during optogenetic photo-stimulation of PVGP terminals in SNc demonstrated that PV-GP neurons strongly inhibited dopamine neurons via GABA(A) receptors. These results suggest that dopamine neurons receive direct focal inputs from PV-GP prototypic neurons. The identification of high-contrast inhibitory systems on dopamine neurons might represent a key step toward understanding the BG function. - Kazuko Mizutani, Susumu Takahashi, Shinichiro Okamoto, Fuyuki Karube, Fumino FujiyamaBRAIN STRUCTURE & FUNCTION 222 (9) 4089 - 4110 1863-2653 2017/12 [Refereed][Not invited]
Previous studies have suggested that the neurokinin-1 receptor (NK-1R) expressing neurons in the globus pallidus (GP) receive substance P (SP), presumably released by axon collaterals of striatal direct neurons. However, the effect of SP on the GP remains unclear. In this study, we identified that the SP-responsive cells comprise a highly specific cell type in the GP with regard to immunofluorescence, electrophysiology, and projection properties. Morphologically, NK-1R-immunoreactive neurons occasionally co-expressed parvalbumin (PV) and/or Lim-homeobox 6 (Lhx6), but not Forkhead box protein P2 (FoxP2), which is mainly expressed by arkypallidal neurons. Retrograde tracing experiments also showed that some of GP neurons projecting to the subthalamic nucleus (namely prototypic neurons) expressed NK-1R as well as Lhx6 and/or PV, but not FoxP2. In vitro electrophysiological study revealed that, among 48 GP neurons, the SP agonist induced inward current in 21 neurons. The response was prevented by bath application of the NK-1R antagonist. Based on the firing properties, 92 recorded GP neurons were classified into three distinct types, i.e., CL1, 2, and 3. Interestingly, all the SP-responsive neurons were found to be in CL2 and CL3 types, but not in CL1. Moreover, active and passive membrane properties of the neurons in those clusters and immunofluorescent identification suggested that CL1 and CL2/3 could be considered as arkypallidal and prototypic neurons, respectively. Therefore, SP-responsive neurons were one of the populations of prototypic neurons based on both anatomical and electrophysiological results. Altogether, the striatal direct pathway neurons could affect the indirect pathway in the way of prototypic neurons, via the action of SP to NK-1R. - Fuyuki Karube, Katalin Sari, Zoltan F. KisvardayBRAIN STRUCTURE & FUNCTION 222 (3) 1401 - 1426 1863-2653 2017/04 [Refereed][Not invited]
To uncover the functional topography of layer 6 neurons, optical imaging was combined with three-dimensional neuronal reconstruction. Apical dendrite morphology of 23 neurons revealed three distinct types. Type Aa possessed a short apical dendrite with many oblique branches, Type Ab was characterized by a short and less branched apical dendrite, whereas Type B had a long apical dendrite with tufts in layer 2. Each type had a similar number of boutons, yet their spatial distribution differed from each other in both radial and horizontal extent. Boutons of Type Aa and Ab were almost restricted to the column of the parent soma with a laminar preference to layer 4 and 5/6, respectively. Only Type B contributed to long horizontal connections (up to 1.5 mm) mostly in deep layers. For all types, bouton distribution on orientation map showed an almost equal occurrence at iso- (52.6 +/- 18.8 %) and non-iso-orientation (oblique, 27.7 +/- 14.9 % and cross-orientation 19.7 +/- 10.9 %) sites. Spatial convergence of axons of nearby layer 6 spiny neurons depended on soma separation of the parent cells, but only weakly on orientation preference, contrary to orientation dependence of converging axons of layer 4 spiny cells. The results show that layer 6 connections have only a weak dependence on orientation preference compared with those of layers 2/3 (Buzas et al., J Comp Neurol 499:861-881, 2006) and 4 (Karube and Kisvarday, Cereb Cortex 21:1443-1458, 2011). - Perineuronal nets in the deep cerebellar nuclei regulate GABAergic transmission and delay eyeblink conditioningHirono M, Watanabe S, Karube F, Fujiyama F, Kawahara S, Nagao S, Yanagawa Y, Misonou HJ Neurosci 291 51 2017 [Refereed][Not invited]
- Katsuya Yamada, Susumu Takahashi, Fuyuki Karube, Fumino Fujiyama, Kazuto Kobayashi, Akinori Nishi, Toshihiko MomiyamaJOURNAL OF PHYSIOLOGICAL SCIENCES 66 (6) 435 - 446 1880-6546 2016/11 [Refereed][Not invited]
The authors have reviewed recent research advances in basal ganglia circuitry and function, as well as in related disorders from multidisciplinary perspectives derived from the results of morphological, electrophysiological, behavioral, biochemical and molecular biological studies. Based on their expertise in their respective fields, as denoted in the text, the authors discuss five distinct research topics, as follows: (1) area-specific dopamine receptor expression of astrocytes in basal ganglia, (2) the role of physiologically released dopamine in the striatum, (3) control of behavioral flexibility by striatal cholinergic interneurons, (4) regulation of phosphorylation states of DARPP-32 by protein phosphatases and (5) physiological perspective on deep brain stimulation with optogenetics and closed-loop control for ameliorating parkinsonism. - Yoshiyuki Kubota, Fuyuki Karube, Masaki Nomura, Yasuo KawaguchiFRONTIERS IN NEURAL CIRCUITS 10 27 1662-5110 2016/04 [Refereed][Not invited]
The most typical and well known inhibitory action in the cortical microcircuit is a strong inhibition on the target neuron by axo-somatic synapses. However, it has become clear that synaptic inhibition in the cortex is much more diverse and complicated. Firstly, at least ten or more inhibitory non-pyramidal cell subtypes engage in diverse inhibitory functions to produce the elaborate activity characteristic of the different cortical states. Each distinct non-pyramidal cell subtype has its own independent inhibitory function. Secondly, the inhibitory synapses innervate different neuronal domains, such as axons, spines, dendrites and soma, and their inhibitory postsynaptic potential (IPSP) size is not uniform. Thus, cortical inhibition is highly complex, with a wide variety of anatomical and physiological modes. Moreover, the functional significance of the various inhibitory synapse innervation styles and their unique structural dynamic behaviors differ from those of excitatory synapses. In this review, we summarize our current understanding of the inhibitory mechanisms of the cortical microcircuit. - Yoshiyuki Kubota, Satoru Kondo, Masaki Nomura, Sayuri Hatada, Noboru Yamaguchi, Alsayed A. Mohamed, Fuyuki Karube, Joachim Luebke, Yasuo KawaguchiELIFE 4 2050-084X 2015/07 [Refereed][Not invited]
Inhibitory interneurons target precise membrane regions on pyramidal cells, but differences in their functional effects on somata, dendrites and spines remain unclear. We analyzed inhibitory synaptic events induced by cortical, fast-spiking (FS) basket cells which innervate dendritic shafts and spines as well as pyramidal cell somata. Serial electron micrograph (EMg) reconstructions showed that somatic synapses were larger than dendritic contacts. Simulations with precise anatomical and physiological data reveal functional differences between different innervation styles. FS cell soma-targeting synapses initiate a strong, global inhibition, those on shafts inhibit more restricted dendritic zones, while synapses on spines may mediate a strictly local veto. Thus, FS cell synapses of different sizes and sites provide functionally diverse forms of pyramidal cell inhibition. - Fumino Fujiyama, Susumu Takahashi, Fuyuki KarubeFrontiers in Neuroscience 9 6 1662-453X 2015 [Refereed][Not invited]
Electrophysiological studies in monkeys have shown that dopaminergic neurons respond to the reward prediction error. In addition, striatal neurons alter their responsiveness to cortical or thalamic inputs in response to the dopamine signal, via the mechanism of dopamine-regulated synaptic plasticity. These findings have led to the hypothesis that the striatum exhibits synaptic plasticity under the influence of the reward prediction error and conduct reinforcement learning throughout the basal ganglia circuits. The reinforcement learning model is useful however, the mechanism by which such a process emerges in the basal ganglia needs to be anatomically explained. The actor-critic model has been previously proposed and extended by the existence of role sharing within the striatum, focusing on the striosome/matrix compartments. However, this hypothesis has been difficult to confirm morphologically, partly because of the complex structure of the striosome/matrix compartments. Here, we review recent morphological studies that elucidate the input/output organization of the striatal compartments. - Kei Oyama, Shinya Ohara, Sho Sato, Fuyuki Karube, Fumino Fujiyama, Yoshikazu Isomura, Hajime Mushiake, Toshio Iijima, Ken-Ichiro TsutsuiJournal of Neuroscience Methods 218 (2) 139 - 147 0165-0270 2013/09/15 [Refereed][Not invited]
In order to make a direct link between the morphological and functional study of the nervous system, we established an experimental protocol for labeling individual neurons persistently without microscopic guidance by injecting a plasmid encoding fluorescent protein electroporatively after recording their activity extracellularly. Using a glass pipette filled with electrolyte solution containing a plasmid encoding green fluorescent protein (GFP), single-neuron recording and electroporation were performed on anesthetized rats. When performing the electroporation at the completion of recording, the degree of contact between the target neuron and the electrode tip was adjusted by monitoring the change of the trace of recorded action potentials and the increase of electrode resistance. The expression of GFP and its immunostaining with a polyclonal antibody enabled us to clearly see the basic structural components such as cell bodies, axons, dendrites, and even smaller components such as spines. Identification of the morphological subtypes of neurons was possible with every labeled neuron. The optimum condition for labeling was a 30% increase of the electrode resistance, and the labeling success rate evaluated 3 days after labeling was 40%. The rate evaluated one month after labeling was only slightly lower (33%). We also confirmed experimentally that this recording and labeling procedure can be similarly successful in head-fixed behaving rats. This new experimental protocol will be a breakthrough in systems neuroscience because it makes a direct link between the morphology and behavior-related activity of single neurons. © 2013 Elsevier B.V. - Yasuharu Hirai, Mieko Morishima, Fuyuki Karube, Yasuo KawaguchiJOURNAL OF NEUROSCIENCE 32 (5) 1898 - 1913 0270-6474 2012/02 [Refereed][Not invited]
How information is manipulated and segregated within local circuits in the frontal cortex remains mysterious, in part because of inadequate knowledge regarding the connectivity of diverse pyramidal cell subtypes. The frontal cortex participates in the formation and retrieval of declarative memories through projections to the perirhinal cortex, and in procedural learning through projections to the striatum/pontine nuclei. In rat frontal cortex, we identified two pyramidal cell subtypes selectively projecting to distinct subregions of perirhinal cortex (PRC). PRC-projecting cells in upper layer 2/3 (L2/3) of the frontal cortex projected to perirhinal area 35, while neurons in L5 innervated perirhinal area 36. L2/3 PRC-projecting cells partially overlapped with those projecting to the basolateral amygdala. L5 PRC-projecting cells partially overlapped with crossed corticostriatal cells, but were distinct from neighboring corticothalamic (CTh)/corticopontine cells. L5 PRC-projecting and CTh cells were different in their electrophysiological properties and dendritic/axonal morphologies. Within the frontal cortex, L2/3 PRC-projecting cells innervated L5 PRC-projecting and CTh cells with similar probabilities, but received feedback excitation only from PRC-projecting cells. These data suggest that specific neuron subtypes in different cortical layers are reciprocally excited via interlaminar loops. Thus, two interacting output channels send information from the frontal cortex to different hierarchical stages of the parahippocampal network, areas 35 and 36, with additional collaterals selectively targeting the amygdala or basal ganglia, respectively. Combined with the hierarchical connectivity of PRC-projecting and CTh cells, these observations demonstrate an exquisite diversification of frontal projection neurons selectively connected according to their participation in distinct memory subsystems. - Yoshiyuki Kubota, Fuyuki Karube, Masaki Nomura, Allan T. Gulledge, Atsushi Mochizuki, Andreas Schertel, Yasuo KawaguchiSCIENTIFIC REPORTS 1 (89) doi:10.1038/srep00089 2045-2322 2011/09 [Refereed][Not invited]
Dendritic trees influence synaptic integration and neuronal excitability, yet appear to develop in rather arbitrary patterns. Using electron microscopy and serial reconstructions, we analyzed the dendritic trees of four morphologically distinct neocortical interneuron subtypes to reveal two underlying organizational principles common to all. First, cross-sectional areas at any given point within a dendrite were proportional to the summed length of all dendritic segments distal to that point. Consistent with this observation, total cross-sectional area was almost perfectly conserved at bifurcation points. Second, dendritic cross-sections became progressively more elliptical at more proximal, larger diameter, dendritic locations. Finally, computer simulations revealed that these conserved morphological features limit distance dependent filtering of somatic EPSPs and facilitate distribution of somatic depolarization into all dendritic compartments. Because these features were shared by all interneurons studied, they may represent common organizational principles underlying the otherwise diverse morphology of dendritic trees. - Yoshiyuki Kubota, Naoki Shigematsu, Fuyuki Karube, Akio Sekigawa, Satoko Kato, Noboru Yamaguchi, Yasuharu Hirai, Mieko Morishima, Yasuo KawaguchiCEREBRAL CORTEX 21 (8) 1803 - 1817 1047-3211 2011/08 [Refereed][Not invited]
Whether neocortical gamma-aminobutyric acid (GABA) cells are composed of a limited number of distinct classes of neuron, or whether they are continuously differentiated with much higher diversity, remains a contentious issue for the field. Most GABA cells of rat frontal cortex have at least 1 of 6 chemical markers (parvalbumin, calretinin, alpha-actinin-2, somatostatin, vasoactive intestinal polypeptide, and cholecystokinin), with each chemical class comprising several distinct neuronal subtypes having specific physiological and morphological characteristics. To better clarify GABAergic neuron diversity, we assessed the colocalization of these 6 chemical markers with corticotropin-releasing factor (CRF), neuropeptide Y (NPY), the substance P receptor (SPR), and nitric oxide synthase (NOS); these 4 additional chemical markers suggested to be expressed diversely or specifically among cortical GABA cells. We further correlated morphological and physiological characteristics of identified some chemical subclasses of inhibitory neurons. Our results reveal expression specificity of CRF, NPY, SPR, and NOS in morphologically and physiologically distinct interneuron classes. These observations support the existence of a limited number of functionally distinct subtypes of GABA cells in the neocortex. - Fuyuki Karube, Zoltan F. KisvardayCEREBRAL CORTEX 21 (6) 1443 - 1458 1047-3211 2011/06 [Refereed][Not invited]
Our aim was to reveal the relationship between layer IV horizontal connections and the functional architecture of the cat primary visual cortex because these connections play important roles in the first cortical stage of visual signals integration. We investigated bouton distribution of spiny neurons over an orientation preference map using in vivo optical imaging, unit recordings, and single neuron reconstructions. The radial extent of reconstructed axons (14 star pyramidal and 9 spiny stellate cells) was similar to 1.5 mm. In the vicinity of the parent somata (< 400 mu m), boutons occupied chiefly iso-orientations, however, more distally, 7 cells projected preferentially to non-iso-orientations. Boutons of each cell were partitioned into 1-15 distinct clusters based on the mean-shift algorithm, of which 57 clusters preferred iso-orientations and 43 clusters preferred cross-orientations, each showing sharp orientation preference "tuning." However, unlike layer III/V pyramidal cells preferring chiefly iso-orientations, layer IV cells were engaged with broad orientations because each bouton cluster from the same cell could show different orientation preference. These results indicate that the circuitry of layer IV spiny cells is organized differently from that of iso-orientation dominant layer III/V cells and probably processes visual signals in a different manner from that of the superficial and deeper layers. - Kubota Yoshiyuki, Karube Fuyuki, Nomura Masaki, Gulledge Allan T, Mochizuki Atsushi, Kawaguchi YasuoNEUROSCIENCE RESEARCH 68 E12 0168-0102 2010 [Refereed][Not invited]
- Giorgio A. Ascoli, Lidia Alonso-Nanclares, Stewart A. Anderson, German Barrionuevo, Ruth Benavides-Piccione, Andreas Burkhalter, Gyoergy Buzsaki, Bruno Cauli, Javier DeFelipe, Alfonso Fairen, Dirk Feldmeyer, Gord Fishell, Yves Fregnac, Tamas F. Freund, Daniel Gardner, Esther P. Gardner, Jesse H. Goldberg, Moritz Helmstaedter, Shaul Hestrin, Fuyuki Karube, Zoltan F. Kisvarday, Bertrand Lambolez, David A. Lewis, Oscar Marin, Henry Markram, Alberto Munoz, Adam Packer, Carl C. H. Petersen, Kathleen S. Rockland, Jean Rossier, Bernardo Rudy, Peter Somogyi, Jochen F. Staiger, Gabor Tamas, Alex M. Thomson, Maria Toledo-Rodriguez, Yun Wang, David C. West, Rafael YusteNATURE REVIEWS NEUROSCIENCE 9 (7) 557 - 568 1471-003X 2008/07 [Refereed][Not invited]
Neuroscience produces a vast amount of data from an enormous diversity of neurons. A neuronal classification system is essential to organize such data and the knowledge that is derived from them. Classification depends on the unequivocal identification of the features that distinguish one type of neuron from another. The problems inherent in this are particularly acute when studying cortical interneurons. To tackle this, we convened a representative group of researchers to agree on a set of terms to describe the anatomical, physiological and molecular features of GABAergic interneurons of the cerebral cortex. The resulting terminology might provide a stepping stone towards a future classification of these complex and heterogeneous cells. Consistent adoption will be important for the success of such an initiative, and we also encourage the active involvement of the broader scientific community in the dynamic evolution of this project. - Masakazu Uematsu, Yasuharu Hirai, Fuyuki Karube, Satoe Ebihara, Megumi Kato, Kuniya Abe, Kunihiko Obata, Sachiko Yoshida, Masumi Hirabayashi, Yuchio Yanagawa, Yasuo KawaguchiCEREBRAL CORTEX 18 (2) 315 - 330 1047-3211 2008/02 [Refereed][Not invited]
Although neocortical GABAergic (gamma-aminobutyric acidergic) interneurons have been the focus of intense study, especially in the rat, a consensus view of the functional diversity and organization of inhibitory cortical neurons has not yet been achieved. To better analyze GABAergic neurons in the rat, we used a bacterial artificial chromosome (BAC) construct and established 2 lines of transgenic rats that coexpress Venus, a yellow fluorescent protein, with the vesicular GABA transporter. The brain GABA content from both transgenic lines was similar to the level found in wild-type rats. In the frontal cortex, Venus was expressed in >95% of GABAergic neurons, most of which also expressed at least one of 6 biochemical markers, including alpha-actitin-2, which preferentially labeled late-spiking neurogliaform cells. Taking advantage of the fact that Venus expression allows for targeted recording from all classes of nonpyramidal cells, irrespective of their somatic morphologies, we demonstrated that fast-spiking neurons, which were heterogeneous in somatic size as well as vertical dendritic projection, had relatively uniform horizontal dimensions, suggesting a cell type-specific columnar input territory. Our data demonstrate the benefits of VGAT-Venus rats for investigating GABAergic circuits, as well as the feasibility of using BAC technology in rats to label subsets of specific, genetically defined neurons. - Kubota Yoshiyuki, Karube Fuyuki, Nomura Masaki, Aoyagi Toshio, Mochizuki Atsushi, Kawaguchi YasuoNEUROSCIENCE RESEARCH 58 S73 0168-0102 2007 [Refereed][Not invited]
- Yoshiyuki Kubota, Sayuri Hatada, Satoru Kondo, Fuyuki Karube, Yasuo KawaguchiJOURNAL OF NEUROSCIENCE 27 (5) 1139 - 1150 0270-6474 2007/01 [Refereed][Not invited]
Fast inhibition in the cortex is gated primarily at GABAergic synapses formed by local interneurons onto postsynaptic targets. Although GABAergic inputs to the somata and axon initial segments of neocortical pyramidal neurons are associated with direct inhibition of action potential generation, the role of GABAergic inputs to distal dendritic segments, including spines, is less well characterized. Because a significant proportion of inhibitory input occurs on distal dendrites and spines, it will be important to determine whether these GABAergic synapses are formed selectively by certain classes of presynaptic cells onto specific postsynaptic elements. By electron microscopic observations of synapses formed by different subtypes of nonpyramidal cells, we found that a surprisingly large fraction (33.4 +/- 9.3%) of terminals formed symmetrical synaptic junctions onto a subset of cortical spines that were mostly coinnervated by an asymmetrical terminal. Using VGLUT1 and VGLUT2 isoform of the glutamate vesicular transporter immunohistochemistry, we found that the double-innervated spines selectively received thalamocortical afferents expressing the VGLUT2 but almost never intracortical inputs expressing the VGLUT1. When comparing the volumes of differentially innervated spines and their synaptic junction areas, we found that spines innervated by VGLUT2-positive terminal were significantly larger than spines innervated by VGLUT1-positive terminal and that these spines had larger, and more often perforated, synapses than those of spines innervated by VGLUT1-positive afferent. These results demonstrate that inhibitory inputs to pyramidal cell spines may preferentially reduce thalamocortical rather than intracortical synaptic transmission and are therefore positioned to selectively gate extracortical information. - Y Kawaguchi, F Karube, Y KubotaCEREBRAL CORTEX 16 (5) 696 - 711 1047-3211 2006/05 [Refereed][Not invited]
To understand the dendritic differentiation in various types of cortical nonpyramidal cells, we analyzed quantitatively their dendritic branching and spine expression. The dendritic internode and interspine interval obeyed exponential distributions with type-specific decay constants. The initial branching pattern, internode interval and spine density at the light microscopic level divided nonpyramidal cells into three dendritic types, correlated with axonal, neurochemical and firing types. The initial branching pattern determined the overall vertical spread of dendrites. Basket cell subtypes with different firing and chemical expression patterns were distinct in the vertical and horizontal spatial spread, providing diverse input territories. Internode densities of dendritic spines, as well as those of axonal synaptic boutons, did not correlate with the tortuosities and intervals, suggesting a tendency to distribute synapses homogeneously over the arbor. Dendritic spines identified at the electron microscopic level were different in length and shape among subtypes. Although the density was lower than that of pyramidal cells, spines themselves were also composed of several morphological types such as mushroom and multihead ones, which were expressed differentially among subtypes. Correlation of dendritic branching characteristics with differences in spine structure suggests distinct ways to receive specific inputs among the subtypes. - F Karube, Y Kubota, Y KawaguchiJOURNAL OF NEUROSCIENCE 24 (12) 2853 - 2865 0270-6474 2004/03 [Refereed][Not invited]
GABAergic nonpyramidal cells, cortical interneurons, consist of heterogeneous subtypes differing in their axonal field and target selectivity. It remains to be investigated how the diverse innervation patterns are generated and how these spatially complicated, but synaptically specific wirings are achieved. Here, we asked whether a particular cell type obeys a specific branching and bouton arrangement principle or differs from others only in average morphometric values of the morphological template common to nonpyramidal cells. For this purpose, we subclassified nonpyramidal cells within each physiological class by quantitative parameters of somata, dendrites, and axons and characterized axon branching and bouton distribution patterns quantitatively. Each subtype showed a characteristic set of vertical and horizontal bouton spreads around the somata. Each parameter, such as branching angles, internode or interbouton intervals, followed its own characteristic distribution pattern irrespective of subtypes, suggesting that nonpyramidal cells have the common mechanism for formation of the axon branching pattern and bouton arrangement. Fitting of internode and interbouton interval distributions to the exponential indicated their apparent random occurrence. Decay constants of the fitted exponentials varied among nonpyramidal cells, but each subtype expressed a particular set of interbouton and internode interval averages. The distinctive combination of innervation field shape and local axon phenotypes suggests a marked functional difference in the laminar and columnar integration properties of different GABAergic subtypes, as well as the subtype-specific density of inhibited targets. - Fuyuki Karube, Masahiko KobayashiArchives of Insect Biochemistry and Physiology 42 (2) 111 - 118 0739-4462 1999 [Refereed][Not invited]
Mating results in a strong suppression of sex pheromone (bombykol) production in the female silkworm moth, Bombyx mori. The mechanical stimulation from the insertion of a penis, inflation of the bursa copulatrix (BC), or copulation with the sterile male whose penis was removed in order to prevent ejaculation (pr-male) induced only a partial decline in bombykol production. Artificial insemination stimulates oviposition of fertilized eggs as does normal mating. However, bombykol production did not decline in artificially inseminated females. When females were artificially inseminated before or after mating with pr-males, some females had a small amount of bombykol, similar to females mated with normal males, while other females had a large amount of bombykol similar to virgin females. The former usually laid fertilized eggs, while the latter laid only unfertilized eggs though semen filled their spermatophores and spermathecae. The mechanical stimulation caused by mating with a pr-male could be replaced by covering the abdominal tip with melted paraffin. Neither implantation of the BC obtained from mated females, nor injection of the spermatophore extract, into a female mated with a pr-male could inactivate bombykol production. Injection of hemolymph from a mated female into a virgin also failed to affect bombykol production These results indicate that a combination of both the tactile stimulation of the abdominal tip and the arrival of fertile spermatozoa in the vestibulum trigger a neural inactivation mechanism of bombykol production after mating. Arch. Insect Biochem. Physiol. 42:111-118, 1999. © 1999 Wiley-Liss, Inc. - Fuyuki Karube, Masahiko KobayashiJournal of Insect Physiology 45 (10) 947 - 957 0022-1910 1999 [Refereed][Not invited]
In the silkmoth, Bombyx mori, mating accelerates egg laying. Sterilized males did not induce females to oviposit, whereas artificial insemination was enough to accelerate oviposition. These findings showed that mechanical stimulation of the outer reproductive organs and the bursa copulatrix (BC) had no effect on oviposition. Factors included in seminal fluids also did not stimulate oviposition because neither implantation of female internal reproductive organs nor injection of the spermatophore extract into virgin females activated oviposition. Preventing sperm precedence by experimental removal of the BC or spermatheca inhibited activation of egg laying. More precise surgeries on the spermatheca showed that the main factor for eliciting oviposition was the presence of matured and fertile eupyrene spermatozoa in the vestibulum. Sperm were not effective unless they reached the vestibulum. Nerve transection and electrophysiological studies revealed that nerve 4 of the terminal abdominal ganglion was the pathway by which the mating signal was transmitted toward the higher central nervous system.
MISC
- structure and function of basal ganglia藤山文乃, 高橋晋, 苅部冬紀 Clinical Neuroscience 35- 268 -270 2017 [Not refereed][Invited]
- Fumino Fujiyama, Susumu Takahashi, Fuyuki Karube FRONTIERS IN NEUROSCIENCE 9- 2015/02 [Not refereed][Not invited]
Electrophysiological studies in monkeys have shown that dopaminergic neurons respond to the reward prediction error. In addition, striatal neurons alter their responsiveness to cortical or thalamic inputs in response to the dopamine signal, via the mechanism of dopamine-regulated synaptic plasticity. These findings have led to the hypothesis that the striatum exhibits synaptic plasticity under the influence of the reward prediction error and conduct reinforcement learning throughout the basal ganglia circuits. The reinforcement learning model is useful; however, the mechanism by which such a process emerges in the basal ganglia needs to be anatomically explained. The actor critic model has been previously proposed and extended by the existence of role sharing within the striatum, focusing on the striosome/matrix compartments. However, this hypothesis has been difficult to confirm morphologically, partly because of the complex structure of the striosome/matrix compartments. Here, we review recent morphological studies that elucidate the input/output organization of the striatal compartments. - Fuyuki Karube, Zoltan F. Kisvarday NEUROSCIENCE RESEARCH 68- E152 -E152 2010 [Not refereed][Not invited]
- Y. Kawaguchi, F. Karube Encyclopedia of Neuroscience 775 -783 2010 [Not refereed][Not invited]
To understand the structural and functional principles of the neocortex it is essential to identify the functional classes of cortical neurons and their patterns of synaptic connectivity. Neocortical neurons can be divided into two generalized types, excitatory pyramidal cells utilizing glutamate as a transmitter, and nonpyramidal cells that generally release γ-aminobutyric acid as an inhibitory transmitter. Nonpyramidal neurons are extremely heterogeneous in both their dendritic and axonal arborizations. Extensive research over the past decade has defined several basic cellular subtypes, although the specifics of cell classification are still intensely debated. Nonpyramidal cell subtypes have been classified based on a combination of anatomical, physiological, and chemical characteristics, as well as the timing and location of their cellular differentiation. Each subtype shows unique connection selectivity in the cortical circuit. © 2009 Elsevier Ltd All rights reserved. - Yoshiyuki Kubota, Fuyuki Karube, Masaki Nomura, Toshio Aoyagi, Yasuo Kawaguchi NEUROSCIENCE RESEARCH 65- S84 -S84 2009 [Not refereed][Not invited]
- Yoshiyuki Kubota, Fuyuki Karube, Masaki Nomura, Toshio Aoyagi, Yasuo Kawaguchi JOURNAL OF PHYSIOLOGICAL SCIENCES 59- 77 -77 2009 [Not refereed][Not invited]
- 大脳皮質棘突起への興奮性入力と抑制性入力の二重支配窪田 芳之, 畑田 さゆり, 根東 覚, 苅部 冬紀, 川口 泰雄 解剖学雑誌 82- (Suppl.) 225 -225 2007/03 [Not refereed][Not invited]
Books etc
- 大脳基底核 意志と行動の狭間にある神経回路苅部 冬紀, 高橋 晋, 藤山 文乃 (Joint work)
共立出版 2019/07 - 脳科学辞典：錐体細胞2012
- "Structures and Circuits: Cerebral Cortex, Inhibitory cells". In The New Encyclopedia of Neuroscience (ed Squire L)Elsevier, Oxford, UK. 2008