Analysis of Nigral Dopamine Neuron Projections.
Fumino Fujiyama, Fuyuki Karube
Brain and nerve = Shinkei kenkyu no shinpo, 77, 4, 363, 367, Apr. 2025, [Lead author], [Domestic magazines]
Japanese, Scientific journal, Environmental adaptation requires reward prediction errors to be transmitted to the striatum by dopaminergic neurons in the substantia nigra pars compacta of the midbrain. Various methods have been used to visualize the neural circuits involving dopaminergic neurons. In this review, we introduce single-neuron labeling using the membrane-targeting Sindbis virus and Cre-expressing AAV1 as anterograde transsynaptic tracers.

New findings of the basal ganglia.　　　　　　　　　　　　　　　
Fumino Fujiyama
MDSJ Letters, 18, 1, 2025, [Lead author]

Volume electron microscopy for genetically and molecularly defined neural circuits
Ohno N, Karube F, Fujiyama F
Neuroscience Research, Jun. 2024, [Peer-reviewed], [Last author, Corresponding author], [International Magazine]
English, Scientific journal, The brain networks responsible for adaptive behavioral changes are based on the physical connections between neurons. Light and electron microscopy have long been used to study neural projections and the physical connections between neurons. Volume electron microscopy has recently expanded its scale of analysis due to methodological advances, resulting in complete wiring maps of neurites in a large volume of brain tissues and even entire nervous systems in a growing number of species. However, structural approaches frequently suffer from inherent limitations in which elements in images are identified solely by morphological criteria. Recently, an increasing number of tools and technologies have been developed to characterize cells and cellular components in the context of molecules and gene expression. These advancements include newly developed probes for visualization in electron microscopic images as well as correlative integration methods for the same elements across multiple microscopic modalities. Such approaches advance our understanding of interactions between specific neurons and circuits and may help to elucidate novel aspects of the basal ganglia network involving dopamine neurons. These advancements are expected to reveal mechanisms for processing adaptive changes in specific neural circuits that modulate brain functions.

Globus pallidus is not independent from striatal direct pathway neurons: an up-to-date review
Fumino Fujiyama, Fuyuki Karube, Yasuharu Hirai
Mol Brain, 17, 34, 34, 34, Jun. 2024, [Peer-reviewed], [Lead author], [International Magazine]
English, Scientific journal, Striatal projection neurons, which are classified into two groups-direct and indirect pathway neurons, play a pivotal role in our understanding of the brain's functionality. Conventional models propose that these two pathways operate independently and have contrasting functions, akin to an "accelerator" and "brake" in a vehicle. This analogy further elucidates how the depletion of dopamine neurons in Parkinson's disease can result in bradykinesia. However, the question arises: are these direct and indirect pathways truly autonomous? Despite being distinct types of neurons, their interdependence cannot be overlooked. Single-neuron tracing studies employing membrane-targeting signals have shown that the majority of direct pathway neurons terminate not only in the output nuclei, but also in the external segment of the globus pallidus (GP in rodents), a relay nucleus of the indirect pathway. Recent studies have unveiled the existence of arkypallidal neurons, which project solely to the striatum, in addition to prototypic neurons. This raises the question of which type of GP neurons receive these striatal axon collaterals. Our morphological and electrophysiological experiments showed that the striatal direct pathway neurons may affect prototypic neurons via the action of substance P on neurokinin-1 receptors. Conversely, another research group has reported that direct pathway neurons inhibit arkypallidal neurons via GABA. Regardless of the neurotransmitter involved, it can be concluded that the GP is not entirely independent of direct pathway neurons. This review article underscores the intricate interplay between different neuronal pathways and challenges the traditional understanding of their independence.

Pre- and Postembedding Immunoelectron Microscopy to Analyze the Central Nervous System.
Fumino Fujiyama, Fuyuki Karube
Methods in molecular biology (Clifton, N.J.), 2794, 2794, 45, 62, Springer US, 18 Apr. 2024, [Peer-reviewed], [Lead author], [International Magazine]
English, Scientific journal, Immunocytochemistry, a method of delineating the subcellular localization of target proteins, was developed from immunohistochemistry. In principle, proteins are labeled using an antigen-antibody reaction. In order to observe under an electron microscope, the reaction product must scatter the electron beam with sufficient contrast while it is necessary to have an amplifying label that can withstand the observation. We have some detailed tips on making electron microscope samples to achieve this objective, and we would be happy to help you.

Anterograde trans-neuronal labeling of striatal interneurons in relation to dopamine neurons in the substantia nigra pars compacta.
Fuyuki Karube, Yang Yang, Kenta Kobayashi, Fumino Fujiyama
Frontiers in neuroanatomy, 18, 1325368, 1325368, Frontiers Media SA, 28 Feb. 2024, [Peer-reviewed], [Last author], [International Magazine]
English, Scientific journal, Recent advances in neural tracing have unveiled numerous neural circuits characterized by brain region and cell type specificity, illuminating the underpinnings of specific functions and behaviors. Dopaminergic (DA) neurons in the midbrain are highly heterogeneous in terms of gene and protein expression and axonal projections. Different cell types within the substantia nigra pars compacta (SNc) tend to project to the striatum in a cell-type-dependent manner characterized by specific topography. Given the wide and dense distribution of DA axons, coupled with a combination of synaptic and volume transmission, it remains unclear how DA release is spatially and temporally regulated, to appropriately achieve specific behaviors and functions. Our hypothesis posits that hidden rules governing synapse formation between pre-synaptic DA neuron types and striatal neuron types may modulate the effect of DA at a single-cell level. To address this conjecture, we employed adeno-associated virus serotype 1 (AAV1) to visualize the neural circuitry of DA neurons. AAV1 has emerged as a potent anatomical instrument capable of labeling and visualizing pre- and post-synaptic neurons simultaneously through anterograde trans-synaptic labeling. First, AAV1-Cre was injected into the SNc, resulting in Cre expression in both medium spiny neurons and interneurons in the striatum. Due to the potential occurrence of the retrograde transfer of AAV1, only striatal interneurons were considered for trans-synaptic or trans-neuronal labeling. Interneuron types expressing parvalbumin, choline acetyltransferase, somatostatin, or nitrogen oxide synthase exhibited Cre expression. Using a combination of AAV1-Cre and Cre-driven fluorophore expressing AAVs, striatal interneurons and the axons originating from the SNc were visualized in distinct colors. Using immunofluorescence against neurotransmitter transporters, almost all axons in the striatum visualized using this approach were confirmed to be dopaminergic. Moreover, individual DA axons established multiple appositions on the somata and proximal dendrites of interneurons. This finding suggests that irrespective of the extensive and widespread axonal arborization of DA neurons, a particular DA neuron may exert a significant influence on specific interneurons. Thus, AAV1-based labeling of the DA system can be a valuable tool to uncover the concealed rules governing these intricate relationships.

Optogenetic activation of the ventral tegmental area-hippocampal pathway facilitates rapid adaptation to changes in spatial goals.
Yuta Tamatsu, Hirotsugu Azechi, Riku Takahashi, Fumiya Sawatani, Kaoru Ide, Fumino Fujiyama, Susumu Takahashi
iScience, 26, 12, 108536, 108536, Elsevier BV, 15 Dec. 2023, [Peer-reviewed], [International Magazine]
English, Scientific journal, Animal adaptation to environmental goals to pursue rewards is modulated by dopamine. However, the role of dopamine in the hippocampus, involved in spatial navigation, remains unclear. Here, we studied dopaminergic inputs from the ventral tegmental area (VTA) to the hippocampus, focusing on spatial goal persistence and adaptation. Mice with VTA dopaminergic lesions struggled to locate and update learned reward locations in a circular maze with dynamic reward locations, emphasizing the importance of VTA dopaminergic neurons in the persistence and adaptation of spatial memory. Further, these deficits were accompanied by motor impairments or motivational loss even when dopamine receptors in the dorsal hippocampus were selectively blocked. Stimulation of VTA dopaminergic axons within the dorsal hippocampus enhanced the mice's ability to adapt to changing reward locations. These findings provide insights into the contribution of dopaminergic inputs within the hippocampus to spatial goal adaptation.

Empagliflozin attenuates arrhythmogenesis in diabetic cardiomyopathy by normalizing intracellular Ca2+ handling in ventricular cardiomyocytes.
Takahide Kadosaka, Masaya Watanabe, Hiroyuki Natsui, Takuya Koizumi, Motoki Nakao, Taro Koya, Hikaru Hagiwara, Rui Kamada, Taro Temma, Fuyuki Karube, Fumino Fujiyama, Toshihisa Anzai
American journal of physiology. Heart and circulatory physiology, 324, 3, H341-H354, 01 Mar. 2023, [Peer-reviewed], [International Magazine]
English, Scientific journal, Diabetic 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.

Morphological Reevaluation of the Network in Basal Ganglia　　　　　　　　　　　　　　　
Fujiyama F
Clinical Neurophysiology, SE03, 2023, [Peer-reviewed], [Lead author]
English, Scientific journal

Conservation of the Direct and Indirect Pathway Dichotomy in Mouse Caudal Striatum With Uneven Distribution of Dopamine Receptor D1- and D2-Expressing Neurons
Kumiko Ogata, Fuko Kadono, Yasuharu Hirai, Ken-ichi Inoue, Masahiko Takada, Fuyuki Karube, Fumino Fujiyama
Frontiers in Neuroanatomy, Feb. 2022, [Peer-reviewed], [Last author]
English, Scientific journal

Acetylcholine from the nucleus basalis magnocellularis facilitates the retrieval of well-established memory
Shogo Soma, Naofumi Suematsu, Akinori Y Sato, Keisuke Tsunoda, Allen Bramian, Anish Reddy, Koki Takabatake, Fuyuki Karube, Fumino Fujiyama, Satoshi Shimegi
Neurobiology of Learning and Memory, 107484, 107484, Elsevier BV, Jun. 2021, [Peer-reviewed]
English, Scientific journal

Exclusive labeling of direct and indirect pathway neurons in the mouse neostriatum by an adeno-associated virus vector with Cre/lox system
Shinichiro Okamoto, Kenta Yamauchi, Jaerin Sohn, Megumu Takahashi, Yoko Ishida, Takahiro Furuta, Masato Koike, Fumino Fujiyama, Hiroyuki Hioki
STAR Protocols, 2, 1, 100230, 100230, Elsevier BV, Mar. 2021, [Peer-reviewed]
English, Scientific journal

Overlapping Projections of Neighboring Direct and Indirect Pathway Neostriatal Neurons to Globus Pallidus External Segment.
Shinichiro Okamoto, Jaerin Sohn, Takuma Tanaka, Megumu Takahashi, Yoko Ishida, Kenta Yamauchi, Masato Koike, Fumino Fujiyama, Hiroyuki Hioki
iScience, 101409, 101409, 06 Aug. 2020, [Peer-reviewed], [International Magazine]
English, Scientific journal, Indirect pathway medium-sized spiny neurons (iMSNs) in the neostriatum are well known to project to the external segment of the globus pallidus (GPe). Although direct MSNs (dMSNs) also send axon collaterals to the GPe, it remains unclear how dMSNs and iMSNs converge within the GPe. Here, we selectively labeled neighboring dMSNs and iMSNs with green and red fluorescent proteins using an adeno-associated virus vector and examined axonal projections of dMSNs and iMSNs to the GPe in mice. Both dMSNs and iMSNs formed two axonal arborizations displaying topographical projections in the dorsoventral and mediolateral planes. iMSNs displayed a wider and denser axon distribution, which included that of dMSNs. Density peaks of dMSN and iMSN axons almost overlapped, revealing convergence of dMSN axons in the center of iMSN projection fields. These overlapping projections suggest that dMSNs and iMSNs may work cooperatively via interactions within the GPe.

Motor cortex can directly drive the globus pallidus neurons in a projection neuron type-dependent manner in the rat
Fuyuki Karube, Susumu Takahashi, Kenta Kobayashi, Fumino Fujiyama
eLife, 8, e49511, eLife Sciences Publications, Ltd, 12 Nov. 2019, [Peer-reviewed], [Last author]
English, Scientific journal, 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.

Thalamostriatal projections and striosome-matrix compartments.
Fujiyama F, Unzai T, Karube F
Neurochemistry international, 125, 67, 73, Jan. 2019, [Peer-reviewed], [Lead author]
English

Pseudotumor cerebri and lung cancer-associated jugular vein thrombosis: Role of anatomical variations of torcular herophili.
Matsuda W, Noguchi S, Fujiyama F
eNeurologicalSci, 13, 18, 20, Dec. 2018, [Peer-reviewed], [Last author]
English, Scientific journal

Supramammillary Nucleus Afferents to the Dentate Gyrus Co-release Glutamate and GABA and Potentiate Granule Cell Output.
Hashimotodani Y, Karube F, Yanagawa Y, Fujiyama F, Kano M
Cell reports, 25, 10, 2704, 2715, Dec. 2018, [Peer-reviewed]

Anatomical variations of the torcular Herophili: macroscopic study and clinical aspects.
Matsuda W, Sonomura T, Honma S, Ohno S, Goto T, Hirai S, Itoh M, Honda Y, Fujieda H, Udagawa J, Takano S, Fujiyama F, Ueda S
Anatomical science international, 93, 4, 464, 468, Sep. 2018, [Peer-reviewed]

Perineuronal Nets in the Deep Cerebellar Nuclei Regulate GABAergic Transmission and Delay Eyeblink Conditioning.
Hirono M, Watanabe S, Karube F, Fujiyama F, Kawahara S, Nagao S, Yanagawa Y, Misonou H
The Journal of neuroscience : the official journal of the Society for Neuroscience, 38, 27, 6130, 6144, 04 Jul. 2018, [Peer-reviewed]

Parvalbumin-producing striatal interneurons receive excitatory inputs onto proximal dendrites from the motor thalamus in male mice.
Nakano Y, Karube F, Hirai Y, Kobayashi K, Hioki H, Okamoto S, Kameda H, Fujiyama F
Journal of neuroscience research, 96, 7, 1186, 1207, Jul. 2018, [Peer-reviewed]

Substance P effects exclusively on prototypic neurons in mouse globus pallidus.
Mizutani K, Takahashi S, Okamoto S, Karube F, Fujiyama F
Brain structure & function, 222, 9, 4089, 4110, Dec. 2017, [Peer-reviewed]

Continuous membrane potential fluctuations in motor cortex and striatum neurons during voluntary forelimb movements and pauses.
Nonomura S, Fujiwara-Tsukamoto Y, Kajihara T, Fujiyama F, Isomura Y
Neuroscience research, 120, 53, 59, Jul. 2017, [Peer-reviewed]

Quantitative Analyses of the Projection of Individual Neurons from the Midline Thalamic Nuclei to the Striosome and Matrix Compartments of the Rat Striatum.
Unzai T, Kuramoto E, Kaneko T, Fujiyama F
Cerebral cortex (New York, N.Y. : 1991), 27, 2, 1164, 1181, Feb. 2017, [Peer-reviewed]

Using a novel PV-Cre rat model to characterize pallidonigral cells and their terminations.
Oh YM, Karube F, Takahashi S, Kobayashi K, Takada M, Uchigashima M, Watanabe M, Nishizawa K, Kobayashi K, Fujiyama F
Brain structure & function, 222, 5, 2359, 2378, Dec. 2016, [Peer-reviewed]

Neuronal circuits and physiological roles of the basal ganglia in terms of transmitters, receptors and related disorders.
Yamada K, Takahashi S, Karube F, Fujiyama F, Kobayashi K, Nishi A, Momiyama T
The journal of physiological sciences : JPS, 66, 6, 435, 446, Nov. 2016, [Peer-reviewed]

[Morphological Re-evaluation of the Basal Ganglia Network].
Fujiyama F
Brain and nerve = Shinkei kenkyu no shinpo, 68, 7, 861, 864, Jul. 2016, [Peer-reviewed]

A single-neuron tracing study of arkypallidal and prototypic neurons in healthy rats.
Fujiyama F, Nakano T, Matsuda W, Furuta T, Udagawa J, Kaneko T
Brain structure & function, 221, 9, 4733, 4740, Dec. 2015, [Peer-reviewed]

Morphological elucidation of basal ganglia circuits contributing reward prediction.
Fujiyama F, Takahashi S, Karube F
Frontiers in neuroscience, 9, 6, 1, 9, 2015, [Peer-reviewed]
English, Scientific journal

Singular localization of sodium channel β4 subunit in unmyelinated fibres and its role in the striatum.
Miyazaki H, Oyama F, Inoue R, Aosaki T, Abe T, Kiyonari H, Kino Y, Kurosawa M, Shimizu J, Ogiwara I, Yamakawa K, Koshimizu Y, Fujiyama F, Kaneko T, Shimizu H, Nagatomo K, Yamada K, Shimogori T, Hattori N, Miura M, Nukina N
Nature communications, 5, 5525, Nov. 2014, [Peer-reviewed]
Scientific journal

Long-lasting single-neuron labeling by in vivo electroporation without microscopic guidance.
Oyama K, Ohara S, Sato S, Karube F, Fujiyama F, Isomura Y, Mushiake H, Iijima T, Tsutsui K
Journal of neuroscience methods, 218, 2, 139, 147, 2, Sep. 2013, [Peer-reviewed]
Scientific journal

Quantitative analysis of axon bouton distribution of subthalamic nucleus neurons in the rat by single neuron visualization with a viral vector.
Koshimizu Y, Fujiyama F, Nakamura KC, Furuta T, Kaneko T
The Journal of comparative neurology, 521, 9, 2125, 2146, 9, Jun. 2013, [Peer-reviewed]
Scientific journal

Cell type-specific inhibitory inputs to dendritic and somatic compartments of parvalbumin-expressing neocortical interneuron.
Hioki H, Okamoto S, Konno M, Kameda H, Sohn J, Kuramoto E, Fujiyama F, Kaneko T
The Journal of neuroscience : the official journal of the Society for Neuroscience, 33, 2, 544, 555, 2, Jan. 2013, [Peer-reviewed]
Scientific journal

A morphological analysis of thalamocortical axon fibers of rat posterior thalamic nuclei: a single neuron tracing study with viral vectors.
Ohno S, Kuramoto E, Furuta T, Hioki H, Tanaka YR, Fujiyama F, Sonomura T, Uemura M, Sugiyama K, Kaneko T
Cerebral cortex (New York, N.Y. : 1991), 22, 12, 2840, 2857, 12, Dec. 2012, [Peer-reviewed]
Scientific journal

Parvalbumin-producing cortical interneurons receive inhibitory inputs on proximal portions and cortical excitatory inputs on distal dendrites.
Kameda H, Hioki H, Tanaka YH, Tanaka T, Sohn J, Sonomura T, Furuta T, Fujiyama F, Kaneko T
The European journal of neuroscience, 35, 6, 838, 854, 6, Mar. 2012, [Peer-reviewed]
Scientific journal

Local connections of excitatory neurons to corticothalamic neurons in the rat barrel cortex.
Tanaka YR, Tanaka YH, Konno M, Fujiyama F, Sonomura T, Okamoto-Furuta K, Kameda H, Hioki H, Furuta T, Nakamura KC, Kaneko T
The Journal of neuroscience : the official journal of the Society for Neuroscience, 31, 50, 18223, 18236, 50, Dec. 2011, [Peer-reviewed]

Exclusive and common targets of neostriatofugal projections of rat striosome neurons: a single neuron-tracing study using a viral vector.
Fujiyama F, Sohn J, Nakano T, Furuta T, Nakamura KC, Matsuda W, Kaneko T
The European journal of neuroscience, 33, 4, 668, 677, 4, Feb. 2011, [Peer-reviewed]

Complementary distribution of glutamatergic cerebellar and GABAergic basal ganglia afferents to the rat motor thalamic nuclei.
Kuramoto E, Fujiyama F, Nakamura KC, Tanaka Y, Hioki H, Kaneko T
The European journal of neuroscience, 33, 1, 95, 109, 1, Jan. 2011, [Peer-reviewed]

Local connections of layer 5 GABAergic interneurons to corticospinal neurons.
Tanaka YH, Tanaka YR, Fujiyama F, Furuta T, Yanagawa Y, Kaneko T
Frontiers in neural circuits, 5, 12, 2011, [Peer-reviewed]

Vesicular glutamate transporter 3-expressing nonserotonergic projection neurons constitute a subregion in the rat midbrain raphe nuclei.
Hioki H, Nakamura H, Ma YF, Konno M, Hayakawa T, Nakamura KC, Fujiyama F, Kaneko T
The Journal of comparative neurology, 518, 5, 668, 686, 5, Mar. 2010, [Peer-reviewed]

Afferent islands are larger than mu-opioid receptor patch in striatum of rat pups.
Nakamura KC, Fujiyama F, Furuta T, Hioki H, Kaneko T
Neuroreport, 20, 6, 584, 588, 6, Apr. 2009, [Peer-reviewed]

[Anatomical connections of the basal ganglia].
Fujiyama F
Brain and nerve = Shinkei kenkyu no shinpo, 61, 341, 349, 4, Apr. 2009, [Peer-reviewed]

Single nigrostriatal dopaminergic neurons form widely spread and highly dense axonal arborizations in the neostriatum.
Matsuda W, Furuta T, Nakamura KC, Hioki H, Fujiyama F, Arai R, Kaneko T
The Journal of neuroscience : the official journal of the Society for Neuroscience, 29, 2, 444, 453, 2, Jan. 2009, [Peer-reviewed]

Rapid integration of young newborn dentate gyrus granule cells in the adult hippocampal circuitry.
Ide Y, Fujiyama F, Okamoto-Furuta K, Tamamaki N, Kaneko T, Hisatsune T
The European journal of neuroscience, 28, 12, 2381, 2392, 12, Dec. 2008, [Peer-reviewed]

Potential of embryonic stem cell-derived neurons for synapse formation with auditory hair cells.
Matsumoto M, Nakagawa T, Kojima K, Sakamoto T, Fujiyama F, Ito J
Journal of neuroscience research, 86, 14, 3075, 3085, 14, Nov. 2008, [Peer-reviewed]

Paucity of enkephalin production in neostriatal striosomal neurons: analysis with preproenkephalin-green fluorescent protein transgenic mice.
Koshimizu Y, Wu SX, Unzai T, Hioki H, Sonomura T, Nakamura KC, Fujiyama F, Kaneko T
The European journal of neuroscience, 28, 10, 2053, 2064, 10, Nov. 2008, [Peer-reviewed]

Transiently increased colocalization of vesicular glutamate transporters 1 and 2 at single axon terminals during postnatal development of mouse neocortex: a quantitative analysis with correlation coefficient (vol 26, pg 3054, 2007)
Nakamura Kouichi, Watakabe Akiya, Hioki Hiroyuki, Fujiyama Fumino, Tanaka Yasuyo, Yamamori Tetsuo, Kaneko Takeshi
EUROPEAN JOURNAL OF NEUROSCIENCE, 28, 5, 1032, 1046, Sep. 2008, [Peer-reviewed]

Quantification and characterization of GABA-ergic amacrine cells in the retina of GAD67-GFP knock-in mice.
May CA, Nakamura K, Fujiyama F, Yanagawa Y
Acta ophthalmologica, 86, 4, 395, 400, 4, Jun. 2008, [Peer-reviewed]

Morphological analysis of axonal development in newly generated neurons of adult mouse hippocampus
Yoko Ide, Fumino Fujiyama, Keiko Furuta, Nobuaki Tamamaki, Takeshi Kaneko, Tatsuhiro Hisatsune
NEUROSCIENCE RESEARCH, 61, S58, S58, 2008, [Peer-reviewed]
English

Transiently increased colocalization of vesicular glutamate transporters 1 and 2 at single axon terminals during postnatal development of mouse neocortex: a quantitative analysis with correlation coefficient.
Nakamura K, Watakabe A, Hioki H, Fujiyama F, Tanaka Y, Yamamori T, Kaneko T
The European journal of neuroscience, 26, 11, 3054, 3067, 11, Dec. 2007, [Peer-reviewed]

Metabotropic glutamate receptor 4-immunopositive terminals of medium-sized spiny neurons selectively form synapses with cholinergic interneurons in the rat neostriatum.
Kuramoto E, Fujiyama F, Unzai T, Nakamura K, Hioki H, Furuta T, Shigemoto R, Ferraguti F, Kaneko T
The Journal of comparative neurology, 500, 5, 908, 922, 5, Feb. 2007, [Peer-reviewed]

Homozygous GAD65 and heterozygous GAD67 knock-out mice reveal normal retinal development and maintenance despite reduced amounts of GABA.
May CA, Nakamura K, Fujiyama F, Komatsu Y, Yanagawa Y
Acta neuropathologica, 113, 1, 101, 103, 1, Jan. 2007, [Peer-reviewed]

Morphological analysis of axons of newly generated granule cells in adult mouse hippocampus
Yoko Ide, Fumino Fujiyama, Keiko Furuta, Nobuaki Tamamaki, Takeshi Kaneko, Tatsuhiro Hisatsune
NEUROSCIENCE RESEARCH, 58, S209, S209, 2007, [Peer-reviewed]
English

Vesicular glutamate transporter 2 is required for central respiratory rhythm generation but not for locomotor central pattern generation.
Wallén-Mackenzie A, Gezelius H, Thoby-Brisson M, Nygård A, Enjin A, Fujiyama F, Fortin G, Kullander K
The Journal of neuroscience : the official journal of the Society for Neuroscience, 26, 47, 12294, 12307, 47, Nov. 2006, [Peer-reviewed]

Difference in organization of corticostriatal and thalamostriatal synapses between patch and matrix compartments of rat neostriatum.
Fujiyama F, Unzai T, Nakamura K, Nomura S, Kaneko T
The European journal of neuroscience, 24, 10, 2813, 2824, 10, Nov. 2006, [Peer-reviewed]

Postnatal changes in the colocalization of VGluT1 and VGluT2 immunoreactivities at single axon terminals of the mouse neocortex
Nakamura Kouichi, Watakabe Akiya, Hioki Hiroyuki, Fujiyama Fumino, Tanaka Yasuyo, Yamamori Tetsuo, Kaneko Takeshi
NEUROSCIENCE RESEARCH, 55, S81, 2006, [Peer-reviewed]

Postnatal changes of vesicular glutamate transporter (VGluT)1 and VGluT2 immunoreactivities and their colocalization in the mouse forebrain.
Nakamura K, Hioki H, Fujiyama F, Kaneko T
The Journal of comparative neurology, 492, 3, 263, 288, 3, Nov. 2005, [Peer-reviewed]

Erratum: Demonstration of long-range GABAergic connections distributed throughout the mouse neocortex (European Journal of Neuroscience (2005) 21 (1587-1600)
Ryohei Tomioka, Keiko Okamoto, Takahiro Furuta, Fumino Fujiyama, Takuji Iwasato, Yuchio Yanagawa, Kunihiko Obata, Takeshi Kaneko, Nobuaki Tamamaki
European Journal of Neuroscience, 21, 8, 2310, Apr. 2005, [Peer-reviewed]
English, Scientific journal

Demonstration of long-range GABAergic connections distributed throughout the mouse neocortex.
Tomioka R, Okamoto K, Furuta T, Fujiyama F, Iwasato T, Yanagawa Y, Obata K, Kaneko T, Tamamaki N
The European journal of neuroscience, 21, 6, 1587, 1600, 6, Mar. 2005, [Peer-reviewed]

Presynaptic localization of an AMPA-type glutamate receptor in corticostriatal and thalamostriatal axon terminals.
Fujiyama F, Kuramoto E, Okamoto K, Hioki H, Furuta T, Zhou L, Nomura S, Kaneko T
The European journal of neuroscience, 20, 12, 3322, 3330, 12, Dec. 2004, [Peer-reviewed]

Chemically specific circuit composed of vesicular glutamate transporter 3- and preprotachykinin B-producing interneurons in the rat neocortex.
Hioki H, Fujiyama F, Nakamura K, Wu SX, Matsuda W, Kaneko T
Cerebral cortex (New York, N.Y. : 1991), 14, 11, 1266, 1275, 11, Nov. 2004, [Peer-reviewed]

Vesicular glutamate transporter immunoreactivity in the central and peripheral endings of muscle-spindle afferents.
Wu SX, Koshimizu Y, Feng YP, Okamoto K, Fujiyama F, Hioki H, Li YQ, Kaneko T, Mizuno N
Brain research, 1011, 2, 247, 251, 2, Jun. 2004, [Peer-reviewed]

Identification of sympathetic premotor neurons in medullary raphe regions mediating fever and other thermoregulatory functions.
Nakamura K, Matsumura K, Hübschle T, Nakamura Y, Hioki H, Fujiyama F, Boldogköi Z, König M, Thiel HJ, Gerstberger R, Kobayashi S, Kaneko T
The Journal of neuroscience : the official journal of the Society for Neuroscience, 24, 23, 5370, 5380, 23, Jun. 2004, [Peer-reviewed]

Independent inputs by VGLUT2- and VGLUT3-positive glutamatergic terminals onto rat sympathetic preganglionic neurons.
Nakamura K, Wu SX, Fujiyama F, Okamoto K, Hioki H, Kaneko T
Neuroreport, 15, 3, 431, 436, 3, Mar. 2004, [Peer-reviewed]

Substance P and enkephalinergic synapses onto neurokinin-1 receptor-immunoreactive neurons in the pre-Bötzinger complex of rats.
Liu YY, Wong-Riley MT, Liu JP, Wei XY, Jia Y, Liu HL, Fujiyama F, Ju G
The European journal of neuroscience, 19, 1, 65, 75, 1, Jan. 2004, [Peer-reviewed]

Localization of vesicular glutamate transporters and neuronal nitric oxide synthase in rat nucleus tractus solitarii
L.H Lin, R.H Edwards, R.T.J Fremeau, F Fujiyama, T Kaneko, W.T Talman
Neuroscience, 123, 1, 247, 255, Elsevier BV, Jan. 2004
Scientific journal

Cellular localization of three vesicular glutamate transporter mRNAs and proteins in rat spinal cord and dorsal root ganglia.
Oliveira AL, Hydling F, Olsson E, Shi T, Edwards RH, Fujiyama F, Kaneko T, Hökfelt T, Cullheim S, Meister B
Synapse (New York, N.Y.), 50, 2, 117, 129, 2, Nov. 2003, [Peer-reviewed]

Changes of immunocytochemical localization of vesicular glutamate transporters in the rat visual system after the retinofugal denervation.
Fujiyama F, Hioki H, Tomioka R, Taki K, Tamamaki N, Nomura S, Okamoto K, Kaneko T
The Journal of comparative neurology, 465, 2, 234, 249, 2, Oct. 2003, [Peer-reviewed]

Plasma membrane and vesicular glutamate transporter mRNAs/proteins in hypothalamic neurons that regulate body weight.
Collin M, Bäckberg M, Ovesjö ML, Fisone G, Edwards RH, Fujiyama F, Meister B
The European journal of neuroscience, 18, 5, 1265, 1278, 5, Sep. 2003, [Peer-reviewed]

Vesicular glutamate transporters, VGluT1 and VGluT2, in the trigeminal ganglion neurons of the rat, with special reference to coexpression.
Li JL, Xiong KH, Dong YL, Fujiyama F, Kaneko T, Mizuno N
The Journal of comparative neurology, 463, 2, 212, 220, 2, Aug. 2003, [Peer-reviewed]

Evidence for a glutamatergic input to pontine preganglionic neurons of the superior salivatory nucleus in rat.
Lin LH, Agassandian K, Fujiyama F, Kaneko T, Talman WT
Journal of chemical neuroanatomy, 25, 4, 261, 268, 4, Jul. 2003, [Peer-reviewed]

Expression of vesicular glutamate transporters, VGluT1 and VGluT2, in axon terminals of nociceptive primary afferent fibers in the superficial layers of the medullary and spinal dorsal horns of the rat.
Li JL, Fujiyama F, Kaneko T, Mizuno N
The Journal of comparative neurology, 457, 3, 236, 249, 3, Mar. 2003, [Peer-reviewed]

Differential distribution of vesicular glutamate transporters in the rat cerebellar cortex
H Hioki, F Fujiyama, K Taki, R Tomioka, T Furuta, N Tamamaki, T Kaneko
Neuroscience, 117, 1, 1, 6, Elsevier BV, Mar. 2003
Scientific journal

Honeycomb-like mosaic at the border of layers 1 and 2 in the cerebral cortex.
Ichinohe N, Fujiyama F, Kaneko T, Rockland KS
The Journal of neuroscience : the official journal of the Society for Neuroscience, 23, 4, 1372, 1382, 4, Feb. 2003, [Peer-reviewed]

Relationship between two types of vesicular glutamate transporters and neurokinin-1 receptor-immunoreactive neurons in the pre-Bötzinger complex of rats: light and electron microscopic studies.
Liu YY, Wong-Riley MT, Liu JP, Jia Y, Liu HL, Fujiyama F, Ju G
The European journal of neuroscience, 17, 1, 41, 48, 1, Jan. 2003, [Peer-reviewed]

Synaptic localization of GABA(A) receptor subunits in the substantia nigra of the rat: effects of quinolinic acid lesions of the striatum.
Fujiyama F, Stephenson FA, Bolam JP
The European journal of neuroscience, 15, 12, 1961, 1975, 12, Jun. 2002, [Peer-reviewed]

Complementary distribution of vesicular glutamate transporters in the central nervous system.
Kaneko T, Fujiyama F
Neuroscience research, 42, 4, 243, 250, 4, Apr. 2002, [Peer-reviewed]

Immunohistochemical localization of candidates for vesicular glutamate transporters in the rat brain.
Kaneko T, Fujiyama F, Hioki H
The Journal of comparative neurology, 444, 1, 39, 62, 1, Feb. 2002, [Peer-reviewed]

Immunocytochemical localization of candidates for vesicular glutamate transporters in the rat cerebral cortex.
Fujiyama F, Furuta T, Kaneko T
J Comp Neurol, 435, 3, 379, 387, 2001, [Peer-reviewed]
English, Scientific journal

Synaptic localization of GABA (A) receptor subunits in the striatum of the rat.
Fujiyama F, Fritschy JM, Stephenson FA, Bolam JP
J Comp Neurol, 416, 2, 158, 172, 2000, [Peer-reviewed]
English, Scientific journal

Association of dopaminergic terminals and neurons releasing nitric oxide in the rat striatum: an electron microscopic study using NADPH-diaphorase histochemistry and tyrosine hydroxylase immunohistochemistry.
Fujiyama F, Masuko S
Brain Res Bull, 40, 2, 121, 127, 1996, [Peer-reviewed]
English, Scientific journal

Eicosanoids are produced by microglia, not by astrocytes, in rat glial cell cultures.
Matsuo M, Hamasaki Y, Fujiyama F, Miyazaki S
Brain Res, 685, 1-2, 201, 204, 1995, [Peer-reviewed]
English, Scientific journal

Autopsy report of primary CNS B-cell lymphoma indistinguishable from multiple sclerosis: diagnosis with the immunoglobulin gene rearrangements analysis.
Kuroda Y, Kawasaki T, Haraoka S, Fujiyama F, Kakigi R, Abe M, Tabuchi K, Kuroiwa T, Kishikawa T, Sugihara H
J Neurol Sci, 111, 2, 173, 179, 1992, [Peer-reviewed]
English, Scientific journal

Systemic interferon-alpha in the treatment of HTLV-I-associated myelopathy.
Kuroda Y, Kurohara K, Fujiyama F, Takashima H, Endo C, Matsui M, Neshige R, Kakigi R
Acta Neurol Scand, 86, 1, 82, 86, 1992, [Peer-reviewed]
English, Scientific journal

Analysis of factors of relevance to rapid clinical progression in HTLV-I-associated myelopathy.
Kuroda Y, Fujiyama F, Nagumo F
J Neurol Sci, 105, 1, 61, 66, 1991, [Peer-reviewed]
English, Scientific journal

Event-related brain potentials as indicators of visual recognition and detection of criminals by their use.
Neshige R, Kuroda Y, Kakigi R, Fujiyama F, Matoba R, Yarita M, Luders H, Shibasaki H
Forensic Sci. Int, 51, 1, 95, 103, 1991, [Peer-reviewed]
English, Scientific journal

ダイバーシティ推進委員会 最初の２年　　　　　　　　　　　　　　　
Fumino Fujiyama, Acta anatomica Nipponica, 98, 1, 3, 2023
Japanese

Results of Questionnaire Survey on Efforts to Increase Research-Oriented Doctors and on the Role of Japanese Association of Anatomists in Fostering Young Investigators (March 2017)
八木沼 洋行, 松村 讓兒, 藤山 文乃, 中村 桂一郎, 網塚 憲生, 一條 裕之, 瀬藤 光利, 柴田 昌宏, 渡辺 雅彦, 解剖学雑誌 = Acta anatomica Nipponica, 92, 2, 8, Sep. 2017
日本解剖学会, Japanese

Phasic Firings of Neurons in Motor Cortex and Striatum during Spindle on Electrocorticogram Signals
黒宮 光平, 塚元 葉子, 酒井 裕, 礒村 宜和, 藤山 文乃, 佐村 俊和, 電子情報通信学会技術研究報告 = IEICE technical report : 信学技報, 116, 424, 49, 52, 26 Jan. 2017
電子情報通信学会, Japanese

structure and function of basal ganglia　　　　　　　　　　　　　　　
藤山文乃, 高橋晋, 苅部冬紀, Clinical Neuroscience, 35, 268, 270, 2017, [Invited]

ドパミンと神経機能 基底核回路とドパミン
藤山文乃, 月刊神経内科, 85, 5, 460‐463, 25 Nov. 2016
Japanese

Results of Questionnaire Survey on Gross Anatomy Education (March 2014)
八木沼 洋行, 松村 讓兒, 佐藤 洋一, 飯野 哲, 鶴尾 吉宏, 大和田 祐二, 藤山 文乃, 網塚 憲生, 解剖学雑誌 = Acta anatomica Nipponica, 91, 4, 33, 40, Sep. 2016
日本解剖学会, Japanese

Morphological Re-evaluation of the Basal Ganglia Network
藤山文乃, Brain and Nerve, 68, 7, 0861‐0864, 01 Jul. 2016
Japanese

大脳基底核ネットワークの解析
藤山文乃, 臨床神経生理学, 43, 5, 300, 01 Oct. 2015
Japanese

姿勢・歩行―Something new?伝導路を見る 大脳基底核を巡る伝導路
高橋晋, 藤山文乃, Clin Neurosci, 33, 7, 767, 771, 01 Jul. 2015
Japanese

大脳基底核回路の形態学的解析
藤山文乃, 日本神経回路学会誌, 21, 3, 132, 135, 05 Sep. 2014
大脳基底核を病変の主座とするパーキンソン病やハンチントン病の主症状として，随意運動の障害や不随意運動が認められることから，大脳基底核が運動の実行や調節に関わっていることは明らかであろう．また，近年では黒質－線条体のドーパミン系を中心に強化学習などの新たな機能的側面も注目されている．運動と学習，この二つを大脳基底核はいかにして同時に手がけているのであろうか．筆者は大脳基底核を形態学的のみ観察してきたため，この疑問に直接答えることはできない．しかし解析を進める中で，大脳基底核には大脳皮質や小脳にはない形態学的な特徴があり，この特徴こそが大脳基底核が複数のミッションを同時に遂行できる鍵ではないかとの思いを持っている．まだまだ道半ばではあるが，研究の途中経過を報告する．, Japanese Neural Network Society, Japanese

単一ニューロン可視化技術でみる基底核回路
藤山文乃, Front Parkinson Dis, 7, 3, 148, 151, 31 Aug. 2014
Japanese

パーキンソン病のVisual View 単一ニューロン可視化技術でみる基底核回路
藤山 文乃, Frontiers in Parkinson disease, 7, 3, 148, 151, Aug. 2014
メディカルレビュー社, Japanese

大脳基底核の神経回路
藤山文乃, パーキンソン病・運動障害疾患コングレスプログラム・抄録集, 8th, 49, 2014
Japanese

Decision Making―意思決定・行動選択の神経科学 意思決定・行動選択の神経科学 大脳基底核の神経回路
藤山文乃, Clin Neurosci, 32, 1, 30, 32, 01 Jan. 2014
Japanese

予測と意思決定の神経科学 報酬予測を作る大脳基底核回路の形態学的解明
藤山文乃, 生体の科学, 64, 4, 309, 313, 15 Aug. 2013
Japanese

Morphological re-evaluation of the network in basal ganglia
藤山 文乃, 生体の科学, 64, 4, 309, 313, Jul. 2013
金原一郎記念医学医療振興財団 ; 1949-, Japanese

運動系視床皮質投射の神経回路
倉本恵梨子, 藩世秀, 大野幸, 田中康裕, 雲財知, 古田貴寛, 日置寛之, 中村公一, 藤山文乃, 金子武嗣, 日本解剖学会総会・全国学術集会講演プログラム・抄録集, 118th, 79, 2013
Japanese

中脳ドパミン系の投射様式:パーキンソン病の発症に関与する神経基盤についての考察
松田和郎, 古田貴寛, 薗村貴弘, 大原信司, 布施郁子, 武内重二, 山上達人, 安田宗義, 本間智, 中村公一, 日置寛之, 藤山文乃, 金子武嗣, 宇田川潤, 機能的脳神経外科, 51, 60, 66, 15 Dec. 2012
日本定位・機能神経外科学会事務局, Japanese

Novel Single-Neuron-Tracing Method Using Sindbis Viral Vectors
KURAMOTO Eriko, FURUTA Takahiro, HIOKI Hiroyuki, FUJIYAMA Fumino, KANEKO Takeshi, Microscopy, 46, 2, 125, 131, 30 Jun. 2011
日本顕微鏡学会, Japanese

組換えウイルストレーサーによる単一細胞標識法を用いて,ラットの視床後核群ニューロンの軸索分布を解析する
大野幸, 倉本恵梨子, 藤山文乃, 古田貴實, 日置寛之, 田中康裕, 薗村貴弘, 椙山加綱, 金子武嗣, 解剖学雑誌, 86, 2, 61, 01 Jun. 2011
Japanese

Attempt of quantitative analysis of morphological synaptic connectivity by combining focused ion beam milling and scanning electron microscopy (FIB-SEM) and confocal laser-scanning microscope
Takahiro Sonomura, Takahiro Furuta, Tomo Unzai, Wakoto Matsuda, Haruki Iwai, Fumino Fujiyama, Masanori Uemura, Takeshi Kaneko, NEUROSCIENCE RESEARCH, 71, E310, E310, 2011
English, Summary international conference

Immunohistochemical analysis of neocortical inhibitory inputs to PV-expressing neurons with BAC transgenic mice
Hiroyuki Hioki, Michiteru Konno, Shinichiro Okamoto, Hiroshi Kameda, Eriko Kuramoto, Fumino Fujiyama, Takeshi Kaneko, NEUROSCIENCE RESEARCH, 71, E364, E364, 2011
English, Summary international conference

Single subthalamic neurons target the striatum in rat: Complete visualization with a viral vector
Yoshinori Koshimizu, Fumino Fujiyama, Takahiro Furuta, Kouichi C. Nakamura, Takeshi Kaneko, NEUROSCIENCE RESEARCH, 71, E142, E142, 2011
English, Summary international conference

Single-neuron tracing study of thalamocortical projections arising from the rat ventral medial nucleus by using viral vectors
Eriko Kuramoto, Sachi Ohno, Fumino Fujiyama, Takahiro Furuta, Tomo Unzai, Hiroyuki Hioki, Yasuhiro Tanaka, Takeshi Kaneko, NEUROSCIENCE RESEARCH, 71, E89, E89, 2011
English, Summary international conference

Two types of rat pallidofugal projection system revealed by single-neuron tracing study with a viral vector
Fumino Fujiyama, Takashi Nakano, Takahiro Furuta, Eriko Kuramoto, Daichi Hirai, Takeshi Kaneko, NEUROSCIENCE RESEARCH, 71, E139, E139, 2011
English, Summary international conference

神経系構成細胞の分子マーカー 基底核ニューロンの分子マーカー
藤山文乃, Clin Neurosci, 28, 12, 1352, 1354, 01 Dec. 2010
Japanese

ウイルスベクターを用いた単一視床下核ニューロンの形態解析
越水義登, 古田貴寛, 中村公一, 藤山文乃, 金子武嗣, 解剖学雑誌, 85, 2, 77, 01 Jun. 2010
Japanese

ウイルスベクターを用いた単一視床下核ニューロンの形態学解析
越水義登, 古田貴寛, 中村公一, 藤山文乃, 金子武嗣, 解剖学雑誌, 85, Supplement, 167, Mar. 2010
Japanese

Single-neuron tracing study of the external segment of the globus pallidus in rat with a Sindbis viral vector
Fumino Fujiyama, Takashi Nakano, Takahiro Furuta, Takeshi Kaneko, NEUROSCIENCE RESEARCH, 68, E104, E105, 2010
English, Summary international conference

Classification of neocortical inhibitory inputs into the PV-expressing neurons with BAC transgenic mice
Hiroyuki Hioki, Hiroshi Kameda, Shinichiro Okamoto, Michiteru Konno, Fujiyama Fumino, Kaneko Takeshi, NEUROSCIENCE RESEARCH, 68, E156, E156, 2010
English, Summary international conference

A single-neuron analysis of rat subthalamic nucleus: Complete visualization with a viral vector
Yoshinori Koshimizu, Takahiro Furuta, Hiroyuki Hioki, Kouichi Nakamura, Fumino Fujiyama, Takeshi Kaneko, NEUROSCIENCE RESEARCH, 68, E261, E262, 2010
English, Summary international conference

Subcolumnar structures in local inputs of pyramidal neurons onto corticothalamic neurons in rat barrel cortex
Yasuhiro Tanaka, Yasuyo Tanaka, Michiteru Konno, Fumino Fujiyama, Keiko Okamoto-Furuta, Takahiro Sonomura, Hiroshi Kameda, Hiroyuki Hioki, Takahiro Furuta, Kouichi C. Nakamura, Takeshi Kaneko, NEUROSCIENCE RESEARCH, 68, E73, E73, 2010
English, Summary international conference

A morphological analysis of thalamocortical neurons in rat posterior nuclei by single neuron labeling with viral vectors
Sachi Ohno, Eriko Kuramoto, Fumino Fujiyama, Takahiro Furuta, Hiroyuki Hioki, Yasuhiro Tanaka, Takahiro Sonomura, Kazuna Sugiyama, Takeshi Kaneko, NEUROSCIENCE RESEARCH, 68, E157, E157, 2010
English, Summary international conference

Single-neuron tracing study of thalamocortical projections arising from the rat ventral medial nucleus by using viral vectors
Eriko Kuramoto, Fumino Fujiyama, Takahiro Furuta, Tomo Unzai, Hiroyuki Hioki, Yasuhiro Tanaka, Takeshi Kaneko, NEUROSCIENCE RESEARCH, 68, E262, E262, 2010
English, Summary international conference

線条体パッチ・マトリックスと入出力の解析
藤山文乃, 脳の高次機能システム 平成16-21年度 No.16068101, 110, 111, 2010
Japanese

Anatomical Connections of the Basal Ganglia
FUJIYAMA FUMINO, Brain Nerve, 61, 4, 341, 349, 01 Apr. 2009
Japanese

Anatomical connections of the basal ganglia
藤山 文乃, Brain and nerve, 61, 4, 341, 349, Apr. 2009
医学書院, Japanese

Quantitative analysis of single cell projection from midline and intralaminar thalamic nuclei to patch and matrix compartments of rat striatum
Tomo Unzai, Fumino Fujiyama, Eriko Kuramoto, Takeshi Kaneko, NEUROSCIENCE RESEARCH, 65, S177, S177, 2009
English, Summary international conference

Difference between corticostriatal and thalamostriatal afferents to striatal parvalbumin-producing interneuron
Fumino Fujiyama, Hiroshi Kameda, Takeshi Kaneko, NEUROSCIENCE RESEARCH, 65, S71, S71, 2009
English, Summary international conference

The innervation patterns of single subthalamic neurons in rat
Yoshinori Koshimizu, Fumino Fujiyama, Kouichi Nakamura, Takahiro Furuta, Takeshi Kaneko, NEUROSCIENCE RESEARCH, 65, S105, S106, 2009
English, Summary international conference

Postnatal development of striatofugal neurons in the matrix compartment of rat neostriatum: A single axon tracing study
Kouichi Nakamura, Fumino Fujiyama, Takahiro Furuta, Eriko Kuramoto, Takeshi Kaneko, NEUROSCIENCE RESEARCH, 65, S106, S106, 2009
English, Summary international conference

Excitatory and inhibitory inputs to PV-positive cortical neurons: A quantitative analysis with BAC transgenic mice
Hiroshi Kameda, Takahiro Sonomura, Yasuyo Tanaka, Kouichi Nakamura, Fumino Fujiyama, Hiroyuki Hioki, Takeshi Kaneko, NEUROSCIENCE RESEARCH, 65, S132, S132, 2009
English, Summary international conference

Axonal arborization of mesocorticolimbic dopaminergic pathway: a single-cell study
Wakoto Matsuda, Takahiro Furuta, Kouichi Nakamura, Hiroyuki Hioki, Fumino Fujiyama, Osamu Yasuhara, Takeshi Kaneko, NEUROSCIENCE RESEARCH, 65, S188, S188, 2009
English, Summary international conference

Intra- and juxta-columnar projection of cortical pyramidal neurons to corticothalamic neurons in the rat somatosensory cortex
Yasuhiro Tanaka, Yasuyo Tanaka, Michiteru Konno, Fumino Fujiyama, Keiko Okamoto-Furuta, Takahiro Sonomura, Hiroshi Kameda, Hiroyuki Hioki, Takahiro Furuta, Kouichi Nakamura, Takeshi Kaneko, NEUROSCIENCE RESEARCH, 65, S177, S177, 2009
English, Summary international conference

ラット線条体パッチ・マトリックス構造と視床線条体ニューロンの投射様式
雲財知, 藤山文乃, 倉本恵梨子, 金子武嗣, 解剖学雑誌, 83, 2, 67, Jun. 2008
Japanese

線条体パッチ・マトリックスを巡るネットワークを再検討する
藤山文乃, 孫在隣, 中野隆, 雲財知, 金子武嗣, 解剖学雑誌, 83, Supplement, 133, Mar. 2008
Japanese

ラット新生仔線条体のドーパミンアイランドにみられる二重構造
中村公一, 藤山文乃, 古田貴寛, 金子武嗣, 解剖学雑誌, 83, Supplement, 214, Mar. 2008
Japanese

Neural circuits involving patch and matrix compartments of rat neostriatum
Fumino Fujiyama, Jaerin Sohn, Takashi Nakano, Tomo Unzai, Yoshinori Koshimizu, Takeshi Kaneko, NEUROSCIENCE RESEARCH, 61, S12, S12, 2008
English, Summary international conference

Axonal arborization of mesocorticolimbic (A10) dopaminergic pathway: A single-cell study
Wakoto Matsuda, Takahiro Furuta, Kouichi Nakamura, Hiroyuki Hioki, Fumino Fujiyama, Ryohachi Arai, Takeshi Kaneko, NEUROSCIENCE RESEARCH, 61, S258, S258, 2008
English, Summary international conference

Postnatal development of striatofugal neurons in the matrix compartment of rat neostriatum: A single axon tracing study
Kouichi Nakamura, Fumino Fujiyama, Takahiro Furuta, Erika Kuramoto, Takeshi Kaneko, NEUROSCIENCE RESEARCH, 61, S98, S98, 2008
English, Summary international conference

単一ニューロントレースにより線条体パッチ・マトリックスからの投射経路を再検討する
中野隆, 藤山文乃, 雲財知, 野村嶬, 金子武嗣, 形態・機能, 6, 1, 62, 01 Sep. 2007
Japanese

淡蒼球外節に投射する線条体のエンケファリン産生ニューロンは主にマトリックス領域に分布する:トランスジェニックマウスを用いた解析
越水義登, 武勝昔, 雲財知, 藤山文乃, 金子武嗣, 解剖学雑誌, 82, Supplement, 164, Mar. 2007
Japanese

Difference in network between patch and matrix compartment of rat neostriatum
Fujiyama Fumino, Proceedings of Annual Meeting of the Physiological Society of Japan, 2007, 0, 7, 7, 2007
The neostriatum, which possesses a mosaic organization consisting of patch and matrix compartments, receives glutamatergic excitatory afferents from the cerebral cortex and thalamus. Differences in the synaptic organization of these striatopetal afferents between the patch and matrix compartments were examined in the rat using confocal laser scanning and electron microscopes. Thalamostriatal terminals, which were immunopositive for vesicular glutamate transporter (VGluT) 2, were less dense in the patch than in the matrix compartment, although the density of VGluT1-immunopositive corticostriatal terminals was almost evenly distributed in both the compartments. Quantitative analysis of ultrastructural images revealed that 84% of VGluT2-positive synapses in the patch compartment were formed with dendritic spines, whereas 70% in the matrix compartment were made with dendritic shafts. In contrast, VGluT1-positive terminals display a similar preference for specific synaptic targets in both the compartments: about 80% made synapses with dendritic spines. In addition, VGluT2-positive axospinous synapses in the patch compartment were larger than the VGluT1-positive axospinous synapses in both the compartment. Since axospinous synapses are generally found in neuronal connections showing high synaptic plasticity, the present findings suggest that the thalamostriatal connection requires higher synaptic plasticity in the patch compartment than in the matrix compartment. We further demonstrate the output pattern originating from patch and matrix compartments, using single cell tracing with the recombinant Sindbis virus. <b>[J Physiol Sci. 2007;57 Suppl:S7]</b>, PHYSIOLOGICAL SOCIETY OF JAPAN

Single cell tracing of thalamostriatal projection neurons with reference to patch and matrix compartments of rat striatum
Tomo Unzai, Fumino Fujiyama, Takeshi Kaneko, NEUROSCIENCE RESEARCH, 58, S34, S34, 2007
English, Summary international conference

The striatofugal system from patch and matrix compartments in rat neostriatum
Jaerin Sohn, Fumino Fujiyama, Takeshi Kaneko, NEUROSCIENCE RESEARCH, 58, S92, S92, 2007
English, Summary international conference

A reevaluation of the network via patch and matrix compartments of rat neostriatum
Fumino Fujiyama, Jaerin Sohn, Tomo Unzai, Takeshi Kaneko, NEUROSCIENCE RESEARCH, 58, S59, S59, 2007
English, Summary international conference

Presynaptic AMPA receptors on the corticostriatal terminals enhance the release probability of the synaptic vesicles
Takuma Tanaka, Fumino Fujiyama, Masaki Nomura, Toshio Aoyagi, Takeshi Kaneko, NEUROSCIENCE RESEARCH, 58, S211, S211, 2007
English, Summary international conference

Single cell tracing of striatofugal neurons in neonatal rat brain
Kouichi Nakamura, Fumino Fujiyama, Takahiro Furuta, Takeshi Kaneko, NEUROSCIENCE RESEARCH, 58, S212, S212, 2007
English, Summary international conference

Parkinson病 What’s new? 概念と基本 大脳基底核の解剖
藤山文乃, 金子武嗣, Clin Neurosci, 25, 1, 22, 24, 01 Jan. 2007
Japanese

Presynaptic localization of an AMPA-type glutamate receptor in rat neostriatum
FUJIYAMA Fumino, Microscopy, 41, 2, 90, 94, 31 Jul. 2006
日本顕微鏡学会, Japanese

Presynaptic localization of an AMPA-type glutamate receptor in rat neostriatum
FUJIYAMA Fumino, Microscopy, 41, 2, 90, 94, 31 Jul. 2006
日本顕微鏡学会, Japanese

Single cell tracing of thalamostriatal projection neurons with reference to patch and matrix compartments of rat striatum
Tomo Unzai, Fumino Fujiyama, Takeshi Kaneko, NEUROSCIENCE RESEARCH, 55, S195, S195, 2006
English, Summary international conference

Roles of presynaptic AMPA receptors on corticostriatal terminals in up-states of medium-sized spiny neurons
Takuma Tanaka, Fumino Fujiyama, Masaki Nomura, Toshio Aoyagi, Takesi Kaneko, NEUROSCIENCE RESEARCH, 55, S125, S125, 2006
English, Summary international conference

Difference in organization of corticostriatal and thalamostriatal synapses between patch and matrix compartments of rat neostriatum
Fumino Fujiyama, Tomo Unzai, Kouichi Nakamura, Sakashi Nomura, Takeshi Kaneko, NEUROSCIENCE RESEARCH, 55, S195, S195, 2006
English, Summary international conference

グルタミン酸トランスポーターの新たな展開 中枢神経ネットワークにおけるシナプス小胞性グルタミン酸トランスポーター
藤山文乃, 日置寛之, 金子武嗣, 脳21, 8, 4, 405, 410, 20 Oct. 2005
Japanese

脳内神経回路 線条体出力神経への興奮性入力の形態的解析
藤山文乃, ブレインサイエンス・レビュー, 2005, 219, 233, 25 Mar. 2005
Japanese

Identification of sympathetic premotor neurons mediating fever and thermoregulation in the rostral ventromedial medulla
Nakamura Kazuhiro, Kobayashi Shigeo, Kaneko Takeshi, Matsumura Kiyoshi, Huebschle Thomas, Nakamura Yoshiko, Wu Sheng-Xi, Okamoto Keiko, Fujiyama Fumino, Hioki Hiroyuki, Gerstberger Ruediger, Proceedings of Annual Meeting of the Physiological Society of Japan, 2004, 0, S196, S196, 2004
The rostral ventromedial medulla (RVMM) sympathetically regulates thermogenesis in brown adipose tissue (BAT) and constriction of skin blood vessels. However, the sympathetic-related neurons in the RVMM remain to be identified. First, we found that vesicular glutamate transporter 3 (VGLUT3) -immunoreactive neurons in the rostral raphe pallidus nucleus and raphe magnus nucleus expressed Fos in response to both fever-inducing stimulus (central injection of prostaglandin E<SUB>2</SUB>) and cold-exposure (4&deg;C, 4 hours) in rats. Most of the VGLUT3-expressing neurons were negative for serotonin immunoreactivity, and many of them were labeled trans-synaptically with pseudorabies virus inoculated into rat interscapular BAT or tail. Furthermore, we found that the VGLUT3-positive neurons directly project onto sympathetic preganglionic neurons in the intermediolateral cell column (IML) of the spinal cord; and that VGLUT3-positive axon terminals in the IML formed asymmetric synapses, suggesting the excitatory characteristics of the synapses. These results suggest that the rostral medullary raphe regions contain glutamatergic neurons that could be categorized as a novel group of sympathetic premotor neurons involved in fever induction and thermoregulation. <b>[Jpn J Physiol 54 Suppl:S196 (2004)]</b>, PHYSIOLOGICAL SOCIETY OF JAPAN

大脳基底核におけるシナプス小胞性グルタミン酸トランスポーターの解析
藤山文乃, 岡本敬子, 古田貴寛, 玉巻伸章, 金子武嗣, 解剖学雑誌, 78, Supplement, 266, Apr. 2003
Japanese

Comprehensive study of brain. Correlation between glutamate inputs and glutamate receptors that derive from cerebral cortex and thalamus of rat striatum.
FUJIYAMA FUMINO, FURUTA TAKAHIRO, SHIGEMOTO RYUICHI, KANEKO TAKETSUGU, 脳研究の総合的推進に関する研究 平成13年度採択公募班員, 45, 2003
Japanese

Immunocytochemical analysis of vesicular glutamate transporters in the projection neurons of the retina
Fujiyama Fumino, Hioki Hiroyuki, Kaneko Takeshi, Abstracts of the Annual Meeting of the Japanese Association of Anatomists, 107, 0, 80, 80, 07 Jul. 2002
THE JAPANESE ASSOCIATION OF ANATOMISTS

Distribution of vesicular glutamate transporters, VGluT1 and VGluT2, in the cerebellar cortex
Hioki Hiroyuki, Fujiyama Fumino, Okamoto Keiko, Kaneko Takeshi, Abstracts of the Annual Meeting of the Japanese Association of Anatomists, 107, 0, 76, 76, 2002
THE JAPANESE ASSOCIATION OF ANATOMISTS

小脳皮質におけるVesicular glutamate transporterの候補の分布
日置寛之, 藤山文乃, 金子武嗣, 日本神経科学大会プログラム・抄録集, 24th, 249, 26 Sep. 2001
Japanese

ラット脳におけるVesicular glutamate transporterの候補の分布を免疫組織化学的に研究する
金子武嗣, 藤山文乃, 日置寛之, 日本神経科学大会プログラム・抄録集, 24th, 247, 26 Sep. 2001
Japanese

大脳皮質におけるシナプス小胞性グルタミン酸トランスポーターの候補の光顕および電顕的免疫組織学的研究
藤山文乃, 古田貴寛, 金子武嗣, 日本神経科学大会プログラム・抄録集, 24th, 247, 26 Sep. 2001
Japanese

大脳皮質におけるシナプス小胞性グルタミン酸トランスポーターの候補の光顕および電顕的免疫組織学的研究
藤山文乃, 古田貴寛, 金子武嗣, 神経化学, 40, 2/3, 303, 01 Sep. 2001
Japanese

ラット脳におけるVesicular glutamate transporterの候補の分布を免疫組織化学的に研究する
金子武嗣, 藤山文乃, 日置寛之, 神経化学, 40, 2/3, 303, 01 Sep. 2001
Japanese

小脳皮質におけるVesicular glutamate transporterの候補の分布
日置寛之, 藤山文乃, 金子武嗣, 神経化学, 40, 2/3, 305, 01 Sep. 2001
Japanese

Vesivular glutamate transporteer(VGluT)免疫活性によるグルタミン酸作動性神経終末分布の解析
藤山文乃, 金子武嗣, 解剖学雑誌, 76, 1, 142, 01 Feb. 2001
Japanese

Special issue : neuromuscular diseases for practitioners.Practical diagnosis and therapy.Multiple sclerosis.
FUJIYAMA FUMINO, KURODA YASUO, SHIBAZAKI HIROSHI, 月刊臨床と研究, 68, 4, 981, 986, Apr. 1991
Japanese

Burkitt's type ALL with numb chin syndrome as the initial manifestation.
FUJIYAMA FUMINO, MATSUZAKI MIWAKO, SHIMAMOTO YOSHINORI, NOGUCHI TERUO, KURATA YOSHITO, KURODA YASUO, YAMAGUCHI MASAYA, 臨床血液, 32, 2, 152, 155, Feb. 1991
A case of Burkitt's type ALL with numb chin syndrome as the initial manifestation is described. A 57-year-old Japanease male was admitted to our hospital in November 14, 1989 because of paresthesia at the chin and lower lip with diplopia and ptosis. Neurological examination revealed oculomotor paralysis of the right side and hypesthesia on the chin, lower lip and buccal mucous membrane. Laboratory findings showed increased leukocyte count. Bone marrow aspirate revealed hypercellular marrow with 92.3% leukemic cells which had vacuoles in the cytoplasm and surface marker of IgM, κ type. The abnormalities of karyotype included t(8;14). He was treated with chemotherapy and radiation. His conditions were temporarily improved, but relapsed later and died in March 6, 1990. Leukemic infiltrations to the trigeminal nerve were found in autopsy. The relationship between lymphoid malignancies and numb chin syndrome was discussed., The Japanese Society of Hematology, Japanese

多発性硬化症.　　　　　　　　　　　　　　　
藤山文乃, 黒田康夫, 柴崎浩, 月刊 臨床と研究, 別冊, 68, 4, 37, 42, 1991
Japanese

A case of PEP syndrome.
Saika Minoru, Watanabe Hideo, Matsushita Ikuko, Asami Toyoko, Oda Kenichiro, Fujiyama Fumino, Orthopedics & Traumatology, 37, 4, 1770, 1773, Feb. 1989
A case of PEP syndrome (Crow-Fukase syndrome) was reported.The patient was a 30 years old female. She had polyneuropathy, edema, pigmentation and hypertrichosis of bilateral lower limbs. Roentogenograms of 8th thoracic spine and left femur showed osteosclerotic and osteolytic changes.A needle biopsy of left femur showed proliferation of atypical lymphoplasmatoid cells.We started a therapy of radiation on 8th thoracic spine and left femur, and medicated her with prednisolone. After three months pigmentation, edema, and hypertrichosis improved distinctly, but polyneuropathy did not so much.We emphasized the importance of recognition of PEP syndrome and early therapy., 西日本整形・災害外科学会, Japanese

標準生理学（第10版）　　　　　　　　　　　　　　　
大森治紀, 伊佐正, 他
医学書院, 2025, [Contributor]

カンデル神経科学（日本語版第２版）
Kandel, Eric R., Koester, John, Mack, Sarah, Siegelbaum, Steven, 宮下, 保司, 岡野, 栄之, 神谷, 之康, 合田, 裕紀子, 加藤, 総夫(医学), 藤田, 一郎, 伊佐, 正, 定藤, 規弘, 大隅, 典子, 井ノ口, 馨, 笠井, 清登, 第4章日本語訳
メディカル・サイエンス・インターナショナル, Sep. 2022, 9784815730550, xlviii, 1653p, Japanese

Clinical Neuroscience 39(8), 2021　　　　　　　　　　　　　　　
意思決定の神経回路, 952-955
中外医学社, Aug. 2021, [Joint work]

大脳基底核 : 意思と行動の狭間にある神経路
苅部, 冬紀, 高橋, 晋, 藤山, 文乃, 市川, 眞澄
共立出版, Jul. 2019, 9784320057975, x, 151p, 図版 [2] p, Japanese

標準生理学（第9版）
河合, 康明, 黒沢, 美枝子, 鯉淵, 典之, 伊佐, 正, 本間, 研一, 大森, 治紀, 大橋, 俊夫, 第5章F.G
医学書院, Mar. 2019, 9784260034296, xxvii, 1172p, Japanese, [Contributor]

脳神経外科医が知っておくべきニューロサイエンスの知識　　　　　　　　　　　　　　　
監修 橋本信夫, 編集 三國信啓, 深谷親
2015, [Contributor]

カンデル神経科学（日本語版初版）
Kandel, Eric R., Schwartz, James H. (James Harris), Jessell, Thomas M., Siegelbaum, Steven, Hudspeth, A. James, Mack, Sarah, 金澤, 一郎, 宮下, 保司, 岡野, 栄之, 和田, 圭司, 加藤, 総夫(医学), 入來, 篤史, 藤田, 一郎, 伊佐, 正, 定藤, 規弘, 大隅, 典子, 笠井, 清登, 第4章日本語訳
メディカル・サイエンス・インターナショナル, Apr. 2014, 9784895927710, xliii, 1649p, Japanese, [Joint translation]

標準生理学（第8版）
本間, 研一, 大森, 治紀, 大橋, 俊夫, 河合, 康明, 黒沢, 美枝子, 鯉淵, 典之, 伊佐, 正, 小澤, 瀞司, 福田, 康一郎, 第5章F.G
医学書院, Mar. 2014, 9784260017817, xxix, 1140p, Japanese, [Contributor]

中枢神経系の構造. カンデル神経科学　　　　　　　　　　　　　　　
日本語監修, 金澤一郎, 宮下保司
2014, [Joint translation]

線条体. 脳神経科学イラストレイテッド 改訂第三版　　　　　　　　　　　　　　　
羊土社, 2012

大脳基底核の構造（細胞構築と神経回路） Brain and Nerve　　　　　　　　　　　　　　　
医学書院, 2009

線条体パッチ・マトリックス構造における入出力の相違を形態学的に解析する
藤山, 文乃, 京都大学大学院医学研究科
[藤山文乃], 2008, 1冊

脳神経科学イラストレイテッド 改訂第2版　　　　　　　　　　　　　　　
編集 森寿
2006, [Contributor]

電子顕微鏡でみるミクロの世界 生物編　　　　　　　　　　　　　　　
増子貞彦, 藤山文乃, 編集 社団法人日本電子顕微鏡学会, 黒質分離培養神経シナプス.
学際企画, 1995, [Joint work]

電子顕微鏡でみるミクロの世界　　　　　　　　　　　　　　　
社団法人日本電子顕微鏡学会
1995, [Contributor]

Morphological Reevaluation of Basal Ganglia Network　　　　　　　　　　　　　　　
Fumino Fujiyama
Gordon Research Conference, Basal Ganglia, 24 Mar. 2024, English, Invited oral presentation
24 Mar. 2024 - 29 Mar. 2024

大脳基底核の形態学的解析からわかったこと.　　　　　　　　　　　　　　　
藤山文乃
第102回北海道医学大会生理系分科会・第102回日本生理学会北海道地方会, 旭川, 2022, Japanese, Invited oral presentation
2022 - 2022, [Invited]

大脳基底核の形態学的解析.　　　　　　　　　　　　　　　
藤山文乃
日本解剖学会 第68回東北・北海道連合支部学術集会, 札幌, 2022, Japanese, Invited oral presentation
2022 - 2022, [Invited]

大脳基底核回路の再検証.　　　　　　　　　　　　　　　
藤山文乃
第39回日本脳神経外科コングレス総会, 横浜, 2019, Japanese, Others
2019 - 2019, [Invited]

大脳基底核の構造、神経回路と機能.　　　　　　　　　　　　　　　
藤山文乃
第124回日本解剖学会総会・全国学術集会, 新潟, 2019, Japanese, Nominated symposium
2019 - 2019, [Invited]

Neuroanatomical analysis of the rodent basal ganglia network　　　　　　　　　　　　　　　
Fujiyama F
13th International Basal Ganglia Society Meeting, 2019, English, Nominated symposium
2019 - 2019, [Invited]

Basal Ganglia Circuits for Motor and Behavioral, Emotional Performances.　　　　　　　　　　　　　　　
FUJIYAMA Fumino
4th Taiwan International Congress of Parkinson’s Disease and Movement Disorders, Nov. 2018, English, Invited oral presentation
[Invited], [International presentation]

思い通りに動くということ（脳科学の達人）　　　　　　　　　　　　　　　
藤山文乃
第41回日本神経科学大会, 神戸, 2018, Japanese, Public discourse
2018 - 2018, [Invited]

手術に必要な大脳基底核の解剖・生理.　　　　　　　　　　　　　　　
藤山文乃
第41回日本てんかん外科学会・第57回日本定位・機能神経外科学会, 奈良, 2018, Japanese, Public discourse
2018 - 2018, [Invited]

Basal Ganglia Circuits for Motor and Behavioral, Emotional Performances　　　　　　　　　　　　　　　
FUJIYAMA Fumino
21st International Congress of Parkinson’s Disease and Movement Disorders, Jun. 2017, English, Nominated symposium
[Invited], [International presentation]

Using a novel PV-Cre rat model to characterize pallidonigral cells and their terminations　　　　　　　　　　　　　　　
FUJIYAMA Fumino
12th International Basal Ganglia Society Meeting, Mar. 2017, English, Nominated symposium
[Invited], [International presentation]

大脳基底核の構造、神経回路と機能.　　　　　　　　　　　　　　　
藤山文乃
第40回日本神経科学大会, 千葉, 2017, Japanese, Public discourse
2017 - 2017, [Invited]

パーキンソン病と機能神経外科生理学的知見再考.　　　　　　　　　　　　　　　
藤山文乃
第59回日本脳循環代謝学会学術集会, 徳島, 2016, Japanese, Keynote oral presentation
2016 - 2016, [Invited]

パーキンソン病と機能神経外科生理学的知見再考.　　　　　　　　　　　　　　　
藤山文乃
第55回日本定位・機能神経外科学会, 仙台, 2016, Japanese, Keynote oral presentation
2016 - 2016, [Invited]

Quantitative analyses of the thalamic projections to the striosome and matrix compartments of the rat striatum.　　　　　　　　　　　　　　　
藤山文乃
121回日本解剖学会総会・全国学術集会, 福島, 2016, Japanese, Nominated symposium
2016 - 2016, [Invited]

大脳基底核を形態学的に再検証する.　　　　　　　　　　　　　　　
藤山文乃
第38回日本神経科学大会, 神戸, 2015, Japanese, Public discourse
2015 - 2015, [Invited]

組織学・組織学実習　　　　　　　　　　　　　　　
北海道大学
2020 - Present

システム神経科学　　　　　　　　　　　　　　　
同志社大学

神経疾患と創薬　　　　　　　　　　　　　　　
同志社大学

ニューロサイエンス入門　　　　　　　　　　　　　　　
同志社大学

研究安全と倫理　　　　　　　　　　　　　　　
同志社大学

発生学（実習含む）　　　　　　　　　　　　　　　
佐賀医科大学

組織学（実習含む）　　　　　　　　　　　　　　　
佐賀医科大学, 同志社大学

神経解剖学（実習含む）　　　　　　　　　　　　　　　
京都大学, 佐賀医科大学, 同志社大学

肉眼解剖学（実習含む）　　　　　　　　　　　　　　　
京都大学, 佐賀医科大学

運動制御に関わるドーパミン神経回路を投射経路特異的遺伝子発現法により明らかにする
科学研究費助成事業
01 Apr. 2024 - 31 Mar. 2028
藤山 文乃
日本学術振興会, 基盤研究(B), 北海道大学, 24K02777

海馬場所細胞の活動操作によるエピソード記憶神経基盤の解明
科学研究費助成事業
Apr. 2023 - Mar. 2028
高橋 晋, 藤山 文乃, 苅部 冬紀, 畦地 裕統, 井出 薫
日本学術振興会, 基盤研究(A), 同志社大学, 23H00502

行動選択を担う神経投射の多様性構築メカニズム　　　　　　　　　　　　　　　
科学研究費助成事業 学術変革領域研究(A)
10 Sep. 2021 - 31 Mar. 2026
藤山 文乃
日本学術振興会, 学術変革領域研究(A), 北海道大学, 21H05241

Cell type census of adaptive neuronal circuits: biological mechanisms of structural and functional organization
Grants-in-Aid for Scientific Research
Sep. 2021 - Mar. 2026
礒村 宜和, 堀江 健生, 下郡 智美, 藤山 文乃, 佐々木 拓哉, 小林 和人, 郷 康広, 島崎 秀昭
「適応回路センサス」領域では、動物が行動を適応させる脳機能の仕組みを解明するために、神経回路活動の計測操作技術、網羅的な遺伝子発現の解析技術、さらに理論的考証を組み合わせて、新たな視点から適応回路の構築・遷移メカニズムに迫る。総括班の目的は計画研究班や公募研究班の学術交流と連携協力を力強く支援し、次世代の科学を担う若手研究者を育成しつつ、研究成果を国内外に発信して社会にも広く還元することである。
初年度は計画班班員による領域連携体制の構築に集中した。企画運営委員会、研究支援委員会（構造解析、生理解析、行動解析、遺伝子改変、数理・統計各技術班）、遺伝子解析促進委員会（連携解析実施班、連携調整窓口）、若手研究支援委員会、国際活動支援委員会、研究集会委員会、広報委員会、外部評価委員会、事務局を立ち上げた。キックオフシンポジウム、公募説明会、次世代脳シンポジウム、第1回領域会議などを開催し、ホームページを開設した。今後の研究支援活動のためにシングルセル解析用実験装置などを各拠点に取りそろえた。しかしながら、シングルセル解析用セルソーター・ソニーSH800については、新型コロナウイルス感染症パンデミックと世界的な半導体供給不足の影響により納期が大幅に遅延したため、予算を翌年度に繰り越して無事に導入・稼働するに至った。総括班の研究支援により計画班間の連携・共同研究が促進され、公募班の参画を円滑に迎え入れる環境も整えられた。
Japan Society for the Promotion of Science, Grant-in-Aid for Transformative Research Areas (A), Tokyo Medical and Dental University, 21H05238

HFSP Research Grant　　　　　　　　　　　　　　　
HFSP Research Grant
Dec. 2022 - Dec. 2025
https://doi.org/10.52044/HFSP.RGP00482022.pc.gr.153614, Principal investigator

機能的ドーパミン神経細胞サブセットの解明　　　　　　　　　　　　　　　
科学研究費助成事業 基盤研究(B)
01 Apr. 2020 - 31 Mar. 2025
藤山 文乃, 苅部 冬紀, 高橋 晋, 平井 康治, 和久 剛
日本学術振興会, 基盤研究(B), 北海道大学, 20H03549

Understanding episodic memory mechanisms using replay of place cell activity sequences　　　　　　　　　　　　　　　
Grants-in-Aid for Scientific Research Grant-in-Aid for Scientific Research (A)
01 Apr. 2019 - 31 Mar. 2024
高橋 晋, 藤山 文乃, 苅部 冬紀, 井出 薫
本研究では、動物が道に迷い静止した際に、海馬の場所細胞が移動中の約10倍速の早送りモードで再活性化される「リプレイ」現象に着目し、そのリプレイと、そこで表現されるエピソード記憶の因果関係を解明することを目指す。
本年度は、10倍速の早送りモードで再生される場所細胞活動のリプレイを長期間にわたり確実かつ安定に検出し、そこから目標とするリプレイを選択的に操作するために、場所細胞活動を大規模に記録し、光遺伝学に基づく神経刺激技術を確立した。プロトタイプを作成するためのプリント基板の製作や、3D CAD(Computer Aided Design)による設計と3Dプリンタによる製作工程を活用して、遺伝子改変を比較的容易に行うことができるマウスにも装着可能なマイクロドライブを開発した。更に、遺伝子組み換え技術を活用したCre-LoxP部位特異的組換え法により、抑制性のパルバルブミン(PV)陽性ニューロンに対して特異的にChR2を発現させ、場所細胞の集団活動を抑制により操作する試みを実施した。PV陽性ニューロンに特定的にCre組み換え酵素を発現するラット及びマウスを活用し、PV陽性細胞のみを選択的に光操作する実験を分担研究者の藤山や苅部と共同して実施し、その成果の一部を論文として報告した。目標とするエピソードを表現するリプレイを、リプレイ現象の開始直後に予測することで、そのリプレイを消去あるいは強化することができる。そこで、深層学習法により、動物の移動軌跡を追跡するシステムを確立した。
Japan Society for the Promotion of Science, Grant-in-Aid for Scientific Research (A), Doshisha University, 19H01131

Elucidation of Hypobulia and Possibility of Neurotherapeutic Approach in the Very Elderly　　　　　　　　　　　　　　　
Grants-in-Aid for Scientific Research Grant-in-Aid for Challenging Research (Exploratory)
30 Jul. 2020 - 31 Mar. 2023
藤山 文乃, 平井 康治, 苅部 冬紀
Japan Society for the Promotion of Science, Grant-in-Aid for Challenging Research (Exploratory), Hokkaido University, 20K20671

加齢と疾患による大脳基底核神経路の変遷と再構成を検証する　　　　　　　　　　　　　　　
科学研究費助成事業 新学術領域研究(研究領域提案型)
01 Apr. 2020 - 31 Mar. 2022
藤山 文乃
日本学術振興会, 新学術領域研究(研究領域提案型), 北海道大学, 20H05484

Episodic memory retrieval by manipulation of place cell activity
Grants-in-Aid for Scientific Research Grant-in-Aid for Scientific Research (B)
01 Apr. 2016 - 31 Mar. 2020
Takahashi Susumu
We found that theta waves in the hippocampus are deeply involved in memory retrieval related to action plans. Breakthroughs have been made in the development of techniques to manipulate replay phenomena that are reactivated within tens of milliseconds, both in electrophysiological recording methods and in neural stimulation methods using optogenetics. Furthermore, by directly linking these methods in real time, we are developing methods to selectively and real time manipulate the activity of only parvalbumin-positive cells depending on the specific phase of the theta-band LFP. To investigate the retrieval mechanism of episodic memory, we developed a reconfigurable maze and successfully constructed a task to force animals to experience multiple episodes in the same external environment.
Japan Society for the Promotion of Science, Grant-in-Aid for Scientific Research (B), Doshisha University, 16H02840

Investigation of new basal ganglia network　　　　　　　　　　　　　　　
Grants-in-Aid for Scientific Research Grant-in-Aid for Scientific Research (B)
01 Apr. 2016 - 31 Mar. 2020
藤山 文乃, 苅部 冬紀
淡蒼球 (GP: Globus pallidus)は大脳基底核の間接路の中継核である。近年GPにおいて、従来報告されてきた視床下核、脚内核、黒質に投射をする細胞タイプ (Prototypic neuron) とは異なる、線条体のみへ投射をする細胞タイプ (Arkypallidal neuron) が発見された (Fujiyama et al., 2015; Abdi et al., 2015; Dodson et al., 2015)。Arkypallidal neuronの存在は、GPが従来の間接路スキームに則った線条体－GP－脚内核・黒質という単なる一方向の伝達を行っているわけではなく、GP内で計算した情報を線条体にフィードバックしていることを示している。しかしGPの細胞タイプと局所結合の関係は未だ明らかではない。本研究では、この問題を解決するため、GPの局所結合を細胞タイプに分けてその抑制性結合を形態学と電気生理学を用いて調べた。具体的には、Cre-loxPシステムとオプトジェネティクスを組み合わせて、パルブアルブミン(PV)ニューロンを特異的に光刺激によりアクティベートさせ、GPのPVニューロンによるGPニューロンへのGABA-A受容体とGABA-B受容体を介する抑制性シナプス応答を細胞種ごとに明らかにした。GPには、PV発現細胞のほかに、Lhx6もしくはFoxP2を発現する細胞が存在するが、遺伝子組換え動物あるいはウイルスベクターを工夫して組み合わせることで、GP内におけるより詳しい抑制性結合関係を解明しつつあり、この実験経過を国際学会で発表した。これらの研究により投射様式の異なるPrototypic neuronとArkypallidal neuronがどのように情報をやりとりし、大脳基底核間接路の働きを調整しているのかを解明する足がかりになることが期待される。
Japan Society for the Promotion of Science, Grant-in-Aid for Scientific Research (B), Doshisha University, 16H03299

International cooperation for promoting the study of adaptive circuit shift
Grants-in-Aid for Scientific Research Grant-in-Aid for Scientific Research on Innovative Areas (Research in a proposed research area)
06 Nov. 2015 - 31 Mar. 2019
Kobayashi Kazuto
Here we applied our new strategy to manipulate specific neural types and pathways and to characterize dynamic changes of the neural circuit and aimed to elucidate the mechanisms underlying the development and transition of neural circuit during learning processes and the functional compensation of the circuit against neural injury. To achieve this purpose, we focused on the basic technology for neural circuit control (A01), development and transition of neural circuit for behavioral control (A02), and its impairment and recovery of the circuit (A03), organized 9 planned members, and further accepted publicly selected groups (35 groups for the first and second stages, respectively). Based on the integrated research activity including research supporting system, we promoted the interaction and collaboration between research groups.
Japan Society for the Promotion of Science, Grant-in-Aid for Scientific Research on Innovative Areas (Research in a proposed research area), Fukushima Medical University, 15K21715

Experimental research for the surgical target in Parkinson's disease
Grants-in-Aid for Scientific Research Grant-in-Aid for Scientific Research (C)
01 Apr. 2015 - 31 Mar. 2019
Matsuda Wakoto
Dopaminergic neurons in the midbrain mediate a variety of brain functions, such as motor control, emotion, and reward. We studied the axonal arborization of ventral tegmental area (VTA) neurons with Sindbis virus vectors that coded membrane-targeted green fluorescent protein (GFP). After the reconstruction of projection axons, some neurons in VTA were observed to project their axons to the limbic cortices. The other neurons sent axons to the olfactory tubercle, accumbens nucleus, and/or caudate-putamen. Many of these neurons were observed to form relatively high-dense bushes in their terminal fields with ambiguous varicosities. Detail morphological images of neurons derived from this new approach are used to elucidate the role of the neurons in the basal ganglia. These results would also contribute to understanding the clinicopathology of Parkinson’s disease and related syndromes.
Japan Society for the Promotion of Science, Grant-in-Aid for Scientific Research (C), 15K10360

Mechanisms underlying the functional shift of brain neural circuitry for behavioral adaptation
Grants-in-Aid for Scientific Research Grant-in-Aid for Scientific Research on Innovative Areas (Research in a proposed research area)
10 Jul. 2014 - 31 Mar. 2019
Kobayashi Kazuto
Here we applied our new strategy to manipulate specific neural types and pathways and to characterize dynamic changes of the neural circuit and aimed to elucidate the mechanisms underlying the development and transition of neural circuit during learning processes and the functional compensation of the circuit against neural injury. To achieve this purpose, we focused on the basic technology for neural circuit control (A01), development and transition of neural circuit for behavioral control (A02), and its impairment and recovery of the circuit (A03), organized 9 planned members, and further accepted publicly selected groups (35 groups for the first and second stages, respectively). Based on the integrated research activity including research supporting system, we promoted the interaction and collaboration between research groups.
Japan Society for the Promotion of Science, Grant-in-Aid for Scientific Research on Innovative Areas (Research in a proposed research area), Fukushima Medical University, 26112001

Morphological analysis of neurocircuit for adaptive shift
Grants-in-Aid for Scientific Research Grant-in-Aid for Scientific Research on Innovative Areas (Research in a proposed research area)
10 Jul. 2014 - 31 Mar. 2019
Fujiyama Fumino, Karube Fuyuki, Takahashi Susumu
Recent studies revealed that region-specific changes in neural activity in basal ganglia during the different phases of skill learning. The neostriatum has a mosaic organization consisting of striosome and matrix compartments. However, clarifying the input/output organization of striatal compartments has been difficult because of its complex structure. We recently demonstrated that the source of thalamostriatal projections are highly organized in striatal compartments. This finding indicated that the functional properties of striatal compartments are influenced by their cortical and thalamic afferents, presumably with different time latencies. In addition, these afferents likely support the unique dynamics of striosome and matrix compartments. In this manuscript, we review the anatomy of basal ganglia networks with regard to striosome/matrix structure. We place specific focus on thalamostriatal projections at the population and single neuron level.
Japan Society for the Promotion of Science, Grant-in-Aid for Scientific Research on Innovative Areas (Research in a proposed research area), Doshisha University, Principal investigator, Competitive research funding, 26112006

New scheme of the basal ganglia in Parkinson's disease
Grants-in-Aid for Scientific Research Grant-in-Aid for Challenging Exploratory Research
01 Apr. 2015 - 31 Mar. 2018
Fujiyama Fumino
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. Our 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.
Japan Society for the Promotion of Science, Grant-in-Aid for Challenging Exploratory Research, Doshisha University, 15K12770

Parallel functional neural circuitry of the basal ganglia with regard to projection from cerebral cortex
Grants-in-Aid for Scientific Research Grant-in-Aid for Scientific Research (C)
01 Apr. 2014 - 31 Mar. 2018
Karube Fuyuki, FUJIYAMA Fumino
The basal ganglia are important on motor behavior and learning, and also relates to various movement disorders. In this study, we investigated input/output neural circuitry involved in the basal ganglia, cerebral cortex, and thalamus, and found new insights on possible functions of the basal ganglia.
On the external segment of globus pallidus (GPe), one of the relay nuclei of the basal ganglia, we found three main cell population distinguished by molecular expression profiles and electrophysiological properties. One type of them massively inhibited dopaminergic neurons in substantia nigra pars compacta, and also was excited by application of Substance P. We also found direct cortical excitation of GPe neurons. In the striatum, we found parvalbumin-expressing interneurons were innervated by both motor thalamic nuclei and motor cortex and the rules of these two excitatory innervation differed from each other.
Japan Society for the Promotion of Science, Grant-in-Aid for Scientific Research (C), Doshisha University, 26350983

In vivo whole-cell patch-clamp analysis of correlation between ECoG and the membrane potentials of cortical neurons in awake rats.
Grants-in-Aid for Scientific Research Grant-in-Aid for Scientific Research (C)
01 Apr. 2013 - 31 Mar. 2016
Fujiwara-Tsukamoto Yoko, ISOMURA Yoshikazu, FUJIYAMA Fumino
It is said that electrocorticogram (ECoG) reflects the summation of the synchronous activity of post synaptic potentials occured in cortical neurons. However, the generation mehcanisms of ECoG isn't elucidated in detail yet. Since the movement of animals causes the failure of stable whole-cell patch-clamp recordings, the comparison of the fluctuations of membrane potentials with ECoG without anesthesia has been difficult. In this study, we succeeded in stable simultaneous recordings of ECoG and the membrane potentials of pyramidal cells in cortical M1 area or of medium spiny neurons in striatum in awake, task-performing rats. We observed high correlation between membrane potential fluctuations and the wave form of ECoG, and its behavior-related changes were apparent.
Japan Society for the Promotion of Science, Grant-in-Aid for Scientific Research (C), 25430013

Re-evaluation of the basal ganglia network in rat
Grants-in-Aid for Scientific Research Grant-in-Aid for Scientific Research (B)
01 Apr. 2013 - 31 Mar. 2016
Fujiyama Fumino, KARUBE Fuyuki, TAKAHASHI Susumu
A fundamental organizing principle of the striatum is the striosome/matrix system that is defined by inputs/outputs and neurochemical markers. The thalamostriatal projection is highly heterogeneous originating in many subnuclei of the thalamus including the midline (ML) and intralaminar (IL) nuclei. In the striatum, ML neurons preferentially innervated striosomes, whereas parafascicular neurons preferentially innervated the matrix. Almost all single thalamostriatal neurons favoring striosome or matrix compartments also innervated the cerebral cortical area that supplied cortical input to the same striatal compartment. We thus revealed that thalamostriatal projections are highly organized 1) by the similarity in morphological characteristics and 2) their preference for the striatal compartments and cortical areas.
Japan Society for the Promotion of Science, Grant-in-Aid for Scientific Research (B), Doshisha University, Principal investigator, Competitive research funding, 25282247

Development of whole brain recording system
Grants-in-Aid for Scientific Research Grant-in-Aid for Scientific Research (B)
01 Apr. 2012 - 31 Mar. 2016
Takahashi Susumu, FUJIYAMA Fumino, SAKURAI Yoshio
We developed a whole brain recording system which can simultaneously record neuronal activity and EEG over several brain regions. Specifically, using 3D printing technology, we tested the performance of the developed system in a rapid prototyping fashion. Consequently, we made an independently movable microdrive which can access not only deep brain areas but also superficial of the cortex. To evaluate the performance of the system, we recorded place-cell activity while the animal paused. Results suggested that the sequential activation of place-cells are replayed about 10 times faster than that during running. We conclude that our developed system can record both neuronal activity and EEG over several brain regions.
Japan Society for the Promotion of Science, Grant-in-Aid for Scientific Research (B), Doshisha University, 24300148

Comprehensive Brain Science Network
Grants-in-Aid for Scientific Research Grant-in-Aid for Scientific Research on Innovative Areas (Research in a proposed research area)
01 Apr. 2010 - 31 Mar. 2016
Kimura Minoru, Tanji Jun, Takada Masahiko, Nakamura Katsuki, Ohtsuka Toshihisa, Aoki Shigeki, Takao Hidemasa, Shimoji Keigo, Goto Masami, Yoshiura Takashi, Nakata Yasuhiro, Abe Osamu, Masumoto Tomohiko, Tokumaru Aya, Matsumura Akira, Kirino Eiji, Terada Hitoshi, Sato Noriko, Kasai Kiyoto, Hashimoto Ryota, Niwa Shin-ichi, Kato Tadafumi, Suzuki Michio, Shuji Iritani, Nemoto Kiyotaka, Tomita Hiroaki, Murayama Shigeo, Akatsu Hiroyasu, Takao Masaki, Saito Yuko, Bito Haruhiko, Yoshimura Yumiko, Matsuzaki Masanori, Furuta Toshiaki, Okado Haruo, Saito Izumu, Kaibuchi Kozo, Hasegawa Masato, Aiba Atsu, Shiina Nobuyuki, Igarashi Michihiro, Tomoki Nishioka, Watanabe Masahiko, Koike Masato, Sakagami Hiroyuki, Shigemoto Ryuichi, Fukazawa Yugo, Sakimura Kenji, Mori Hisashi, Mishina Masayoshi, Kobayashi Kazuto, Yanagawa Yuchio, Uemura Tadashi, Ishihara Takeshi, Nose Akinao, Iino Yuichi, Miyakawa Tsuyoshi, Takao Keizo, Mushiake Hajime, Katayama Norihiro, Tanaka Tetsu, Inoue Kazuhide, Okabe Shigeo, Kano Masanobu, Fujiyama Fumino, Isa Tadashi, Kageyama Ryoichiro, Fujita Ichiro, Yoshida Akira, Nishikawa Toru, Nukina Nobuyuki, Fukai Tomoki, Iwatsubo Takeshi, Yamamori Tetsuo, Okazawa Hitoshi, Tanaka Keiji, Kakigi Ryusuke, Tsuda Ichiro, Kitazawa Shigeru, Doya Kenji, Takahashi Ryosuke, Ikenaka Kazuhiro, Sobue Gen, Hasegawa Toshikazu, Ota Jun, Saitoe Minoru, Kadomatsu Kenji, Kida Satoshi, Manabe Toshiya, Tomita Taisuke, Iwata Atsushi, Murakami Ikuya, Tsutsui Ken-ichiro, Hanakawa Takashi, Hirai Hirokazu, Mima Tatsuya, Isomura Yoshikazu, Samejima Kazuyuki, Hoshi Eiji, Miyata Mariko, Yuzaki Michisuke, Tanaka Masaki, Fukata Masaki, Suzuki Kyoko, Kuba Hiroshi, Masu Masayuki, Kinoshita Makoto, Sugihara Izumi, Shirane Michiko, Yamamoto Nobuhiko, Nishijo Hisao, Nambu Atsushi, Takumi Toru, Yamashita Toshihide, Sakurai Takeshi, Tamamaki Nobuaki, Hata Yoshio, Harada Akihiro, Ozaki Norio, Sakai Katsuyuki, Kubo Yoshihiro, Nakazawa Takanobu, Tanaka Kenji, Takei Nobuyuki, Hitoshi Seiji, Takahiroa. Kato, Kato Fusao, Shirao Tomoaki, Taira Masato, Okano Hideyuki, Sekino Yuko, Okamoto Yasumasa, KOMATSU Hidehiko, Miyata Takaki, Takahashi Yoshiko, Nishida Shinya, Tominaga Makoto
The Comprehensive Brain Science Network (CSBN) provided individual researches supported by Grant-in-Aid for Scientific Research with cutting-edge resources and technologies, such as model animals, postmortem brain tissue, optical technologies for imaging and manipulation, virus vectors and more. Support covered researches on neuron-specific genes and molecules, synapse, network system, brain functions in disease states and neuro-computation. Special support was directed to collaboration between different fields. Workshop was held to have joint symposia among fields of peoples, to have a special session to let neuroscience community members share knowledge of how current researches are supported in Japan and discuss about future. Graduate students and postdoctoral fellows were supported to visit other laboratories of different field in Japan and abroad and learn disciplines, and award those who presented high quality work the CBSN Prize. These supports promoted break through from conventional approaches and publication of a number of papers with very high quality.
Japan Society for the Promotion of Science, Grant-in-Aid for Scientific Research on Innovative Areas (Research in a proposed research area), Center for Novel Science Initatives, National Institutes of Natural Sciences, 221S0003

ドーパミン放出を抑制する新しい経路の同定
科学研究費助成事業 新学術領域研究(研究領域提案型)
01 Apr. 2014 - 31 Mar. 2015
藤山 文乃
本研究課題では「報酬予測誤差を担うドーパミンニューロンを直接抑制しうる淡蒼球外節ニューロン」を同定する。応募者は前回の公募研究で遺伝子組み換えウイルスベクターによるシングルニューロントレースを用い、視床下核および淡蒼球外節の新しい投射様式を報告した(Koshimizu et al., 2013; Fujiyama et al., Neurosci2013報告)。この研究の過程で、淡蒼球外節ニューロンが黒質緻密部に投射している可能性を偶然発見した。この投射がドーパミンニューロンにシナプス接続するものであれば、ドーパミン放出を直接抑制しうる新しい因子の発見となる。
上記の目的を達成するために、マウスの淡蒼球外節に、順行性トレーサーであるビオチン化デキストランアミン(BDA)を領域ごとに微量注入し、灌流固定後、脳半球全体の連続40μm厚切片を作製した上で、取り込まれたBDAを染色し、可視化した。淡蒼球外節は線条体からの投射の違いを反映するかたちで、抗カルビンディン(CB)抗体を用いた免疫染色により３領域に区分されることが知られている。トレーサーの注入部位はこの３領域を区分したうえで打ち分けた。投射先がドーパミン作動性ニューロンであることを特定するために、ドーパミンの前駆体であるL-ドーパを産生するために必要な酵素であるチロシンヒドロキシラーゼ（TH）に対する免疫染色をおこなった。これにより淡蒼球外節ニューロンの投射軸索とドーパミン作動性ニューロンとのアポジションを確認したため、現在定量解析中である。
日本学術振興会, 新学術領域研究(研究領域提案型), 同志社大学, Principal investigator, Competitive research funding, 26120725

報酬予測をつくるネットワークの解明
科学研究費助成事業 新学術領域研究(研究領域提案型)
01 Apr. 2012 - 31 Mar. 2014
藤山 文乃
1997 年のSchultz の報告から、ドーパミンが報酬の予測誤差を担っているという知見が積み重ねられてきた。しかしこのドーパミンニューロンを直接興奮もしくは抑制しうる因子に何があり得るのかは未だ完全には解明されていない。応募者らは2011年に線条体のストリオソーム（パッチ）領域の直接路ニューロンはドーパミンニューロンが存在する黒質緻密部に投射していることを報告した(Fujiyama et al., 2011)。しかし技術的な限界のために、この報告も黒質緻密部への投射軸索が直接ドーパミンニューロンにシナプスを作成していることの証明までは至らなかった。一方、応募者らはH24～25年の公募研究で、「報酬予測をつくるネットワークの解明」のために大脳基底核の中継核である視床下核および淡蒼球外節に対し、ウイルスベクタを用いた単一神経トレース等を行った (視床下核：Koshimizu et al., 2013; 淡蒼球外節： Fujiyama et al., Neurosci2013報告)。この研究の過程で、淡蒼球外節の単一ニューロンの軸索がドーパミンニューロンが存在する黒質緻密部に投射していることを偶然発見した(Fujiyama et al., Neurosci2013報告)。
日本学術振興会, 新学術領域研究(研究領域提案型), 同志社大学, Principal investigator, Competitive research funding, 24120510

Axonal arborization of dopaminergic neurons of the rat midbrain:mechanism of Parkinson's disease
Grants-in-Aid for Scientific Research Grant-in-Aid for Scientific Research (C)
2010 - 2012
MATSUDA Wakoto, UDAGAWA Jun, FUJIYAMA Fumino, HONMA Satoru, SONOMURA Takahiro, FURUTA Takahiro, YASUHARA Osamu, YASUDA Muneyoshi
The axonal arbors of nigrostriatal dopaminergicneurons were visualized with a viral vector expressing membrane-targeted green fluorescent protein in rat brain. As results, all eight reconstructed tyrosine hydoroxylase-positive dopaminergic neurons possessed widely spread and highly dense axonal arborizations in the neostriatum. The striatal axonal bush of each reconstructed dopaminergic neurons covered 0.45 - 5.7% (mean ± S.D. = 2.7 ± 1.5%) of the total volume of the neostriatum. Furthermore, all the dopaminergic neurons innervated both striosome and matrix compartments of the neostriatum, although each neuron's arborization tended to favor one of these compartments. Detail morphological images of DA neurons derived from this new approach are used to elucidate the role of DA neurons in PD. Firstly, we point out how the new images reveal how DA neurons have a massive axonal arborization in the striatum. This arborization is on a scale not previously known, and of a form that implies both a particular vulnerability and a redundancy in DA neurons. Secondly, we describe how the imaging results indicate that DA neurons innervate both the striosome and the matrix compartments of the striatum. This dual innervation has implications for reinforcement learning in the basal ganglia,with further implications for how normal behavior is driven and how it may be disrupted by Levodopa PD therapies. In conclusion, these results would also contribute to understanding the clinicopathology of Parkinson's disease and related syndromes
Japan Society for the Promotion of Science, Grant-in-Aid for Scientific Research (C), Shiga University of Medical Science, Coinvestigator not use grants, Competitive research funding, 22500307

線条体パッチ・マトリックスと入出力の解析
科学研究費助成事業 特定領域研究
2008 - 2009
藤山 文乃
A. 線条体パッチ・マトリックスへの入力
1. 黒質線条体投射様式(シングルニューロントレース)
従来の報告とは異なり、黒質緻密部の一つのドーパミンニューロンでさえ、パッチ・マトリックスを含む広い範囲に投射する。Matsuda et al.,J Neurosci.,2009
2. 視床線条体投射様式(シングルニューロントレース)
視床線条体投射のうち、髄板内核群、特に束傍核からのものはマトリックス領域を好んで投射する。また、正中線核群からのものはパッチ領域を好んで投射するものが多く、大脳皮質のみならず視床からの投射もパッチ・マトリックス固有の経路が存在することが考えられる(Unzai et al.学会報告)。
3. パッチ・マトリックスの生後発達。Nakamura et al.,Neuro Report, 2009
B. 線条体パッチ・マトリックスからの出力(シングルニューロントレース)
1. パッチ領域にも間接路ニューロンが存在することを見つけた。Fujiyama et al.,submitted
2. パッチの間接路ニューロンはマトリックスのそれと比べてエンケファリン発現量が少ない。Koshimizu et al.,Eur J Neurosci.,2008(エンケファリンBACトランスジェニックマウス)
3. パッチの直接路ニューロンは全て、ドーパミンニューロンが存在する黒質緻密部に投射するが、マトリックスのニューロンが同部位に投射することはない。Fujiyama et al.,submitted
日本学術振興会, 特定領域研究, 京都大学, Principal investigator, Competitive research funding, 20020014

線条体パッチ・マトリックス構造と入出力の形態学的解析
科学研究費助成事業 特定領域研究
2006 - 2007
藤山 文乃
線条体にはパッチ・マトリックスという解剖学的なコンパートメントがあり、近年、強化学習や報酬系における機能的な役割分担の面でも注目されている。しかしながら、大脳基底核の中でこのパッチ・マトリックスを巡るネットワークはどのように違うのか、ということに関しては解明されていない点が多い。まず入力の点から考えると、線条体は大脳皮質と視床から興奮性のグルタミン酸入力を受けているが、皮質線条体入力に比べると、視床線条体入力とパッチ・マトリックス領域との関係はほとんど論じられてきていない。一方、出力に関しては、直接路・間接路という概念とパッチ・マトリックスという解剖学的な構造が同じ線条体内でどのように共存しているのかは未だコンセンサスがない状態である。例えば、パッチのニューロンは本当に黒質緻 密部に投射されるのだろうか、パッチにも直接路・間接路ニューロンともに存在しているのだろうか。また、直接路・間接路の投射形式にはどの程度バリエーションがあるのだろうか。大脳基底核ネットワークをパッチ・マトリックスという視点で再構成するために、シナプス小胞性グルタミン酸トランスポーター(Fujiyama, et. al.,2004.2006)、遺伝子組み換えウイルストレーサー、エンケファリントランスジェニックマウス(Koshimizu, et. al., submitted)等を用いて解析し、大脳基底核ネットワークを検証し、再構築しているところである。
日本学術振興会, 特定領域研究, 京都大学, Principal investigator, Competitive research funding, 18020013

A reevaluation of the network via patch and matrix compartments of rat neostriatum
Grants-in-Aid for Scientific Research Grant-in-Aid for Scientific Research (C)
2006 - 2007
FUJIYAMA Fumino
Neostriatal projection neurons are divided into two groups ; neurons projecting to the substantia nigra (SN) and internal segment of the globus pallidus (GPi) and those projecting to the external segment of the globus pallidus (GPe). The former is called 'direct pathway' neurons in the basal ganglia circuit, since those neurons directly send axons to the output nuclei of the basal ganglia, i.e. pars reticulata of the SN (SNr) and GPi. On the other hand, the latter striato-GPe neurons participate in the 'indirect pathway' which is composed of striato-GPe, GPe-subthalamic and subthalamo-GPi/SNr projections. In addition to the two segregated striatofugal groups, the neostriatum possesses a mosaic organization composed of patch and matrix compartments. The patch compartment occupys 10-15% of the neostriatal volume and characterized by projection to the pars compacta of the SN (SNc). Furthermore, patch regions are visualized with intense immunoreactivity for mu-opioid receptor. In the reinforcement learning, neostriatal neurons in the patch/striosome and matrix compartments are presumed to serve as state-value and action-value functions. However, the way of mutual coexistence of the "direct and indirect pathways" and the " patch and matrix compartments" has not been clarified. To address this question, we examined the striatopetal and striatofugal pathways related with patch and matrix compartments using the recombinant Sindbis virus vector, preproenkephalin/GFP BAC transgenic mouse and vesicular glutamate transporters. With these experiments, we are beginning to clarify the relationship between dual striatofugal system and anatomical compartments, and they will enable us to obtain new scheme of the basal ganglia network.
Japan Society for the Promotion of Science, Grant-in-Aid for Scientific Research (C), Kyoto University, Principal investigator, Competitive research funding, 18500262

Analysis of local neural circuit in the central nervous system
Grants-in-Aid for Scientific Research Grant-in-Aid for Scientific Research (A)
2004 - 2007
KANEKO Takeshi, FUJIYAMA Fumino, FURUTA Takahiro, HIOKI Hiroyuki
To reveal the local circuit in the central nervous system, we examine the circuit under the strategy of 'From one to group'.
1) Single GABAergic neurons were labeled by intracellular staining after whole cell clamp in the cortical slices of adult VGAT/GFP transgenic rats. We analyzed the contacts of these GABAergic axons onto the dendrites of corticospinal neurons, which were retrogradely labeled before the slice preparation.
2) To visualize the whole dendrites of a specific group of neurons, we developed a dendritic membrane-targeted reporter protein (myrGFP-LDLRCT) using a test system of lentiviral vectors. We further produced three kinds of transgenic mice with Thy1 promoter, GAD67 short promoter, and parvalbumin BAC promoter. In all the mice, we found that the dendrites and cell bodies of a specific neuron group were completely labeled with GFP fluorescence or immunofluorescence. Thus, we can now use these mice in the 'From one to group' study combining with an intracellular staining technique.
3) To visualize the whole dendrites of a specific group of neurons, we also developed a viral vectors for retrograde labeling. We have tried pseudorabies virus, rabies virus glycoprotein (RVG)-pseudotyped Sindbis virus, and RVG-pseudotyped lentivirus, and got a partial success in Sindbis virus and lentivirus. In addition, when myrGFP-LDLRCT-expressing adenovirus was injected into the thalamus with 0.6 M NaCl, the dendrites of corticothalamic neurons were efficiently labeled. Thus, we have started the analysis on the local connection of a pyramidal cell to corticothalamic neurons.
4) In the striatum, single medium-sized spiny neurons were labeled with Sindbis virus exressing membrane-targeted GFP. Cortical and thalamic inputs to the single neurons were examined with VGluT1 and VGluT2 immunoreactivities. This may be a 'From group to one' analysis of neural circuit.
Japan Society for the Promotion of Science, Grant-in-Aid for Scientific Research (A), Kyoto University, Coinvestigator not use grants, Competitive research funding, 16200025

中枢神経系の形態学的解析に役立つウィルスベクターを開発する
科学研究費助成事業 萌芽研究
2005 - 2006
金子 武嗣, 藤山 文乃, 古田 貴寛, 日置 寛之
大脳皮質などの中枢神経系の神経回路網についてはその詳細が未だに明らかにされておらず、そのことが中枢神経系の作動原理を理解する際に最も大きな障害となっている。具体的に述べると、従来の神経解剖学的実験法により神経核あるいは皮質の間の神経伝導路の構成についてはある程度判明しているが、それらの内部の神経連絡(局所神経回路)および情報処理に関する多くのことが未知の部分として残っている。例外的に小脳皮質や海馬などのように、旧い技法であるゴルジ染色法によって局所回路のアウトラインを個々のニューロンレベルで描けた部位についてのみ局所回路網の記載が見られるに過ぎず、中枢神経系の作動原理を解明するには、ニューロンの局所連絡を、従来のゴルジ染色法を超える手法によって、個々のニューロンレベルで解析する必要がある。我々は、最近ウィルスベクターを用いたニューロンのゴルジ染色様標識を開発・利用したが、その際ウィルスベクターの有用性を実感した。今年は、我々の研究室で開発・確立してきた遺伝子工学技術を用いて中枢神経系の形態学的研究に有用なベクターを開発することを目的とした。
(1)ニューロンに感染しやすく感染ニューロンの長期生存が可能なレンチウィルスを用いてレポーター蛋白質を検討し、ニコ.ーロンの情報入力部位である樹状突起を選択的に標識するリポーター蛋白質として、myristoylation siteとLDL受容体のC末端を付加したGFPが有用であることを見出した。応用としてトランスジェニックマウスを作製したが、トランスジェニックマウスにおいても樹状突起の選択的標識を確認できた。
(2)経シナプス的に運ばれるリポーター蛋白質をレンチウィルスを用いてニューロンに長期に発現させ、1個の感染ニューロンへ入力する全てのニューロンあるいは1個の感染ニューロンが投射する全てのニューロンを標識することを可能にするウィルスベクター作成の試みについては、CMV enhancer+human synapsin I promoterの組み合わせによりニューロン特異的に長期に渡る強いレポーター蛋白質発現を実現できることを確認できた。
(3)偽狂犬病ウィルスを用いて逆行性にニューロンをゴルジ染色様に標識するベクターを開発したが、感染効率の面でさらに開発をする必要がある。
日本学術振興会, 萌芽研究, 京都大学, Coinvestigator not use grants, Competitive research funding, 17650100

Glutamate receptor in corticostriatal and thalamostriatal axon terminals.
Grants-in-Aid for Scientific Research Grant-in-Aid for Scientific Research (C)
2004 - 2005
FUJIYAMA Fumino, KANEKO Takeshi
(No Summary)
Japan Society for the Promotion of Science, Grant-in-Aid for Scientific Research (C), Kyoto University, Principal investigator, Competitive research funding, 16500217

線条体patchニューロンのネットワーク解析
科学研究費助成事業 特定領域研究
2004 - 2005
藤山 文乃
パーキンソン病やハンチントン病の病変主座である大脳基底核の入力部位は線条体であり、ここにはパッチ・マトリックスという解剖学的なコンパートメントが存在することが知られている。しかし線条体の入出力に関してこのコンパートメントでどのような違いがあるのかは未だ明確にされていない。例えば、入力に関しては各コンパートメントに特異的に入力する大脳皮質領野はわかっているものの視床からの入力パターンの違いはわかっていない。また出力に関しては教科書的にも、直接路・間接路のニューロンともにパッチにもマトリックスにも約半々の割合で分布しており、しかしパッチからの出力は黒質緻密部のドーパミンニューロンであろうという曖昧な記述しかなされていない。この曖昧さの理由として、従来のトレーサー実験では入力元の全てをラベルすることが不可能なこと、また逆に一つのニューロンのみをラベルできずニューロン単位での出力先を追えなかったことが挙げられる。この問題を克服するため、我々はまず入力に関しては、大脳皮質-線条体投射系と視床-線条体投射系の全てを、2種類のシナプス小胞性グルタミン酸トランスポーター(VGluT1,VGluT2)で識別しうることを先行研究(Fujiyama et al., Eur, J.Neurosci., 2004)で明らかにした。このVGluTに対する抗体を用いた免疫組織化学と、パッチに特異的に強く発現するμ-opioid受容体との免疫組織化学(Kaneko et al., 1995)を組み合わせ共焦点顕微鏡および電子顕微鏡による解析を行った。これにより、大脳皮質終末はパッチおよびマトリックスニューロンの樹状突起のスパインにほぼ同程度入力するのに対し、視床終末はマトリックスに比べパッチへの入力が少なく、マトリックスでは樹状突起のシャフトに、パッチではスパインにとシナプスの相手をも替えていることがわかった(Fujiyama et al., submitted)。
日本学術振興会, 特定領域研究, 京都大学, Principal investigator, Competitive research funding, 17022024

新たに発見された線条体の投射ニューロン系
科学研究費助成事業 特定領域研究
2003 - 2004
金子 武嗣, 藤山 文乃, 古田 貴寛
運動系の高次中枢の一つである線条体において神経回路の研究を進めるために、我々は線条体投射ニューロンを免疫学的に識別する手段を開発してきているが、特にNeurokinin B (Neuromedin K)の前駆体であるPreprotachykinin B (PPTB)のC末端に対する抗体を用いて、(1)新線条体には線条体黒質/淡蒼球内節系・線条体淡蒼球外節系以外に今までに報告されていなかった第3の線条体無名質投射系が存在し、(2)この系のみがPPTBを産生してNeurokinin Bを利用していることを明らかにしてきた。本年度はこの研究を以下のように進展させている。
1.腹側線条体にも同様な第3の投射系が存在するかどうか検索した。腹側線条体の側座核にはPPTB陽性のニューロンが存在し、mu-opioid receptor陽性のcell cluster (CC)を形成し、latera lstripe of the striatum (LSS)と連続していることを見出した。さらに、これらのPPTB陽性ニューロンは、無名質を中心に投射しており、それぞれLSSはmedial part of interstitial nucleus of he posterior limb of teh anterior commissure (IPACm)に、LSS-associated CCはbasal component of SI (SIb)に、non-LSS-associated CCはventral part of sublenticular component of SI (SIsl)に投射することを明らかにした。背側線条体のPPTB陽性ニューロンがdorsal most part of SIslに投射していたことを考えると、背側・腹側線条体ともに無名質への第3の投射系が存在していることになる。
2.NK3 receptor (Neurokinin Bの受容体)を発現している無名質ニューロンについて、形態学的・電気生理学的に検討した。NK3発現無名質ニューロンのほとんどはGABA作動性ニューロンであり、大脳皮質へ投射していた。コリン作動性の無名質大脳皮質投射ニューロンと比べると、やや小型で、投射部位についてもコリン作動性ニューロンと違って、感覚系皮質よりは運動皮質により多く投射していた。大脳皮質へ投射するニューロンをホールセルクランプ法で調べたところ、その一部にNK3 agonistに反応するものがあり、膜抵抗が下がって膜電位が上昇する反応が認められた。したがって、NK3受容体はnon-selective cation channelを活性化しているのであろうと推測された。
日本学術振興会, 特定領域研究, 京都大学, Coinvestigator not use grants, Competitive research funding, 15029224

線条体の入出力ニューロンの解析
科学研究費助成事業 特定領域研究
2002 - 2003
藤山 文乃, 金子 武嗣
1,VGluT1,VGluT2を指標にした大脳皮質および視床由来の線条体グルタミン酸終末の同定
大脳基底核は線条体・淡蒼球・視床下核・黒質など大脳皮質下諸核の連合体で大脳皮質および視床からグルタミン酸をトランスミッターとする興奮性入力を受けている.我々は、グルタミン酸神経終末のシナプス小胞性トランスポーターであるVGluTlとVGluT2の抗体をモルモットとウサギとで作製・精製し、この両者が大脳皮質において大脳皮質由来および視床由来のグルタミン酸終末とで使い分けられていることを論文発表し(FUjiyama et al.,J. Comp. Neurol.,2001)、これはトレーサー実験でも証明した。光顕的に観察すると、線条体はVGluT1,VGluT2ともに免疫陽性終末が見られた。さらに2重免疫電顕を行うと、大脳皮質由来の神経終末の70%近くはmedium spiny neuronのspine headに、視床由来の神経終末は60%がdendritc shaftにシナプスしていること、視床由来の神経終末は皮質由来のものより大型であることが観察された。
2.VGluT1,VGluT2を指標にした線条体における大脳皮質および視床由来のグルタミン酸入力とグルタミン酸レセプターとの関係
グルタミン酸レセプターのサブユニットコンフォメーションに対してpresynaptic terminalの違いがどのような影響を与えうるのかを、同じグルタミン酸入力であるVGluT1,VGluT2とグルタミン酸レセプターとの2重免疫電顕にて調べた。イオンチャンネル型グルタミン酸レセプターであるNMDA1,GluR1,GluR2/3はいずれもVGluT1,VGluT2両者とシナプス形成が認められたが、VGluT2陽性シナプスにおいて希に出はあるがpresynaptic siteに存在するGluR2/3が見られた(Fig.1).代謝型グルタミン酸レセプターであるmGluR7では、VGluT1陽性シナプスで陽性、VGluT2陽性シナプスで陰性、と違いが認められた。
日本学術振興会, 特定領域研究, 京都大学, Principal investigator, Competitive research funding, 13035022

Presyriaptic locallzation of AMPA-type glutamate receptor in corticostriatal and thalamostriat axon terminals
Grants-in-Aid for Scientific Research Grant-in-Aid for Scientific Research (C)
2002 - 2003
FUJIYAMA Fumino, KANEKO Takeshi
The neostriatum is known to receive glutamatergic projections from the cerebral cortex and thalamic nuclei. Vesicular glutamate transporters 1 and 2 (VGluT1 and VGluT2) are located on axon terminals of corticostriatal and thalamostriatal inputs, respectively, whereas VGluT3 is found in axon terminals of cholinergic interneurons in the neostriatum. In the present study, the presynaptic localization of ionotropic glutamate receptors was examined in rat neostriatum by the post-embedding immunogold method for double labeling of VGluT and glutamate receptor. Immunoreactive gold particles for AMPA receptor subunits, GluR1-3, were frequently found on presynaptic profiles immunopositive for VGluT1 and VGluT2 in the neostriatum. Quantitative analysis revealed that about 1/4 and 2/5 of GluR2/3-immunopositive particles found in VGluT-positive synapses were associated with presynaptic profiles of VGluT1-and VGluT2-positive axon terminals, respectively, in the neostriatum. In contrast, almost no GluR2/3-immunopositive particles were observed on presynaptic profiles of VGluT3-positive terminals, which made asymmetric synapses in the neostriatum, or on those of VGluT1-or VGluT2-positive terminals in the neocortex. Furthermore, in contrast to GluR1-3, almost no immunoreactivity for GluR4 or NMDA receptor subunit, or only a little immunoreactivity for kainate receptor subunit was found in presynaptic profiles in the neostriatum. The present results suggest that glutamate released from corticostriatal and thalamostriata axon terminals controls the activity of the axon terminals through presynaptic AMPA-type glutamate autoreceptors.
Japan Society for the Promotion of Science, Grant-in-Aid for Scientific Research (C), KYOTO UNIVERSITY, Principal investigator, Competitive research funding, 14580728

Analysis of the local neural circuit in the central nervous system
Grants-in-Aid for Scientific Research Grant-in-Aid for Scientific Research (A)
2000 - 2003
KANEKO Takeshi, FURUTA Takahiro, FUJIYAMA Fumino, TAMAMAKI Nobuaki, KUDO Motoi, TAKI Kousuke
1. Intracortical connections were examined by combining intracellular staining with Golgi-like retrograde labeling of corticofugal neurons. In the motor cortex, 15.2% or 3.8% of varicosities of axon collaterals of the reconstructed layer III pyramidal neurons were apposed to dendrites of corticospinal or corticothalamic neurons, respectively. On the other hand, corticospinal neurons received many collateral inputs from all the cortical layers, suggesting the convergence of information to produce motor output.
2. We have developed adenovirus and Sindbis virus vectors, with which neurons were transduced to express membrane-targeted green fluorescent protein (pGFP). The infected neurons were visualized by fluorescence or immunocytochemistry in a Golgi-atain fashion.
3. We developed a transgenic mouse line which produce pGFP under a control of Kv3.1 potassium channel promoter. We are now analyzing the specificity of expression in GABAergic and thalamic relay neurons.
4. Antibodies to vesicular glutamate transporters (VGluTs) were produced and applied to immunocytochemistry of the brain. VGluT1 and VGluT2 were used by cortical pyramidal neurons and thalamic relay neurons, respectively. Cortical and thalamic excitatory inputs were thus labeled with VGluT1 and VGluT2 selectively in the cerebral cortex and striatum. By combining this VGluT immunostaining with the viral labeling method described above, we are now investigating how many cortical and thalamic inputs enter a cortical or striatal neuron.
5. We reported a third striatofugal pathway, which were characterized by the expression of neurokinin B and projection to the substantia innominata (SI). Some GABAergic SI neurons were found to project to the cerebral cortex and express receptor for neurokin B. Since neurokinin B released from striato-innominatal neurons induced facilitatory effects on the GABAergic innominatocortical neurons, the third pathway may control the cortical activity through those innominatocortical neurons.
Japan Society for the Promotion of Science, Grant-in-Aid for Scientific Research (A), KYOTO UNIVERSITY, Coinvestigator not use grants, Competitive research funding, 12308039

中枢神経系の局所神経回路を解析する
科学研究費助成事業 特定領域研究
2002 - 2002
金子 武嗣, 古田 貴寛, 藤山 文乃
1.Vesicular glutamate transporter (VGluT)を認識する抗体を作成し、中枢神経系の局所神経回路の解析に応用した。VGluT1は主として大脳皮質の出力ニユーロンが使用しており、VGluT2は視床のニューロンが用いているために、線条体・大脳皮質などの領域で、大脳皮質由来および視床由来の興奮性神経終末を区別して標識出来るようになった。Sindbis virusなどの遺伝子工学的手法によりGolgi染色様に標識された一個の大脳皮質ニューロンあるいは線条体ニューロンに、どの様にそれぞれの興奮性入力が入るのか現在解析中である。さらに、VGluT1およびVGluT2の分布を小脳皮質と脊髄後角・延髄後角で調べ、両者が異なる分布をしていることを見出した。小脳皮質では平行線維終末は専らVGluT2を使用し、登上線維はVGluT2を用いていること、面白いことに苔状線維終末にVGLuT1とVGluT2の両方を使用していることなどを明らかにした。一般にVGluT1はsynaptic facilitationを示すシナプスに多く、反対にVGluT2はsynaptic depressionを示すシナプスに認められることから、VGluTの使い分けとこういったシナプスの応答特性との関連が考えられる。
2.今まで線条体のニューロンに今までわかっていた2種類以外に、preprpotachykinin B(PPTB)発現と特異的な無名質投射で特徴づけられる第3の投射系が存在することを明らかにしてきているが、腹側線条体にも同様な第3の投射系が存在するかどうか検索した。腹側線条体の側座核にはPPTB陽性のニューロンが存在し、少なくともその一部は投射ニューロンであることを明らかにした。一方、腹側線条体の嗅結節にはこうしたニューロンが存在せず、嗅結節がこの点で背側線条体・側座核とは異なる組織であることが明らかになった。現在さらに側座核を中心とするPPTB陽性投射系の詳しい投射先を検討している。また、投射先の無名質ニューロンはPPTBの産物であるニューロキニンBに対する受容体を発現しているが、この無名質ニューロンがニューロキニンBに対してどの様な反応を示すか電気生理学的に検索している。
日本学術振興会, 特定領域研究, 京都大学, Coinvestigator not use grants, Competitive research funding, 14017050

新たに発見された線条体の投射ニューロン系
科学研究費助成事業 特定領域研究
2001 - 2002
金子 武嗣, 古田 貴寛, 藤山 文乃
運動系の高次中枢の一つである線条体において神経回路の研究を進めるために、我々は線条体投射ニューロンを免疫学的に識別する手段を開発してきているが、特にNeurokinin B(Neuromedin K)の前駆体であるPreprotachykinin B(PPTB)のC末端に対する抗体を用いて、(1)新線条体には線条体黒質/淡蒼球内節系・線条体淡蒼球外節系以外に今までに報告されていなかった第3の線条体無名質投射系が存在し、(2)この系のみがPPTBを産生してNeurokinin Bを利用していることを明らかにしてきた。本年度はこの研究を以下のように進展させている.
1.腹側線条体にも同様な第3の投射系が存在するかどうか検索した。腹側線条体の側座核にはPPTB陽性のニューロンが存在し、少なくともその一部は投射ニューロンであることを明らかにした。一方、腹側線条体の嗅結節にはこうしたニューロンが存在せず、嗅結節がこの点で背側線条体・側座核とは異なる組織であることが明らかになった。現在さらに側座核を中心とするPPTB陽性投射系の詳しい投射先を検討している。また、投射先の無名質ニューロンはPPTBの産物であるニューロキニンBに対する受容体を発現しているが、この無名質ニューロンがニューロキニンBに対してどの様な反応を示すか電気生理学的に検索している。
2.Vesicular glutamate transporter(VGluT)を認識する抗体を作成し、中枢神経系の局所神経回路の解析に応用した。VGluT1は主として大脳皮質の出力ニューロンが使用しており、VGluT2は視床のニューロンが用いているために、線条体・大脳皮質などの領域で、大脳皮質由来および視床由来の興奮性神経終末を区別して標識出来るようになった。Sindbisvirusなどの遺伝子工学的手法によりGolgi染色様に標識された一個の線条体ニューロンに、どの様にそれぞれの興奮性入力が入るのか現在解析中である。一般にVGluT1はsynaptic facilitationを示すシナプスに多く、反対にVGluT2はsynaptic depressionを示すシナプスに認められることから、VGluTの使い分けとこういったシナプスの応答特性との関連が考えられる。
日本学術振興会, 特定領域研究, 京都大学, Coinvestigator not use grants, Competitive research funding, 13041024

中枢神経系の局所神経回路を解析する
科学研究費助成事業 特定領域研究(C)
2001 - 2001
金子 武嗣, 瀧 公介, 藤山 文乃, 古田 貴寛
1.大脳皮質出力ニューロンを逆行性に細胞体・樹状突起をGolgi染色様に標識する方法により、前もって出力ニューロンを標識したラットの大脳皮質スライス標本を作成した。微小ガラス電極を各層のニューロンに刺入し、基本的な電気的性質を記録してニューロンを分類し、Biocytinを注入した。スライス標本を固定した後、組織学的な検索として免疫蛍光法を用いてBiocytinを注入したニューロンが興奮性あるいは抑制性であるか検討した。次に、Biocytinを注入したニューロンと特にその出力である神経軸索をAvidin-biotinylated peroxi-dase complex法によって青黒色に染色し、逆行性に標識された出力ニューロンの樹状突起をPeroxidase anti-peroxi-dase酵素免疫染色法で赤く染色し、1個のニューロンから一群の大脳皮質投射ニューロンへの連絡を調べた。その結果、興奮性のIII層錐体ニューロンの出力はV層の皮質脊髄投射錐体ニューロンへ多く入力しているが、VI層の皮質視床投射錐体ニューロンへはその4分の1しか入力していないことを見出し報告した。さらに、VI層の錐体ニューロンへの入力を調べII/III層及びV層の錐体ニューロンからの入力は少ないが、IV層・VI層からの入力が多いことを見いだしており、報告をまとめている。
2.中枢神経系の投射ニューロンをアデノウィルスベクターあるいはSindbis virusベクターに感染させ、膜移行シグナルを導入したGreen fluorescent protein(pGFP)を発現させ、Golgi染色様に標識することに成功した。
3.GABA作動性のインターニューロンをGolgi染色様に染色する手法を、トランスジェニックマウスを利用して作ろうとしている。現在、GABAニューロンのマーカーであるParvalbuminとCalretininというカルシウム結合タンパク質の遺伝子をBACを用いてクローニングしている。Calretininトランスジェニックマウスは作成済みで、pGFPの発現特異性を検討している。
日本学術振興会, 特定領域研究(C), 京都大学, Coinvestigator not use grants, Competitive research funding, 13210071

Non-descending inputs to the sympathetic preganglionic neuron and their synaptic structures.
Grants-in-Aid for Scientific Research Grant-in-Aid for Scientific Research (C)
1995 - 1996
MASUKO Sadahiko, FUJIYAMA Fumino, KAWANO Hitoshi, MURATA Yuzo
1) In order to determine non-descending nerve terminals in the intermediolateral nucleus (IML), rat spinal cord was transected at T6 level. Seven days after the operation, serotonin (5-HT)-immunoreactive terminals disappeared completely from the IML of lower spinal cord. However, substance P-, enkephalin-, and tyrosine hydroxylase (TH)-immunoreactive nerve terminals remained in the IML.Electron microscopic observations revealed presence of synaptic contacts between these immunoreactive terminals and IML neurons. This result indicates presence of neuronal inputs from neurons in intrinsic or sub-spinal structures to the sympathetic preganglionic neurons.
2) To examine a possible origin of TH-immunoreactive non-descending terminals in the IML,retrograde neuronal tracing experiments were made. After injection of cholera toxin B (CTB) into the spinal cord of levels T2-13, postganglionic cells located in thoracic sympathetic ganglia (T2-11) were labeled preferentially with CTB.Injections into more rostral (C6) or caudal (L1, L5) spinal cord segments resulted in few labeled ganglion cells. This result suggest that postganglionic neurons in the thoracic sympathetic ganglion project to thoracic spinal cord.
Japan Society for the Promotion of Science, Grant-in-Aid for Scientific Research (C), Saga Medical School, Coinvestigator not use grants, Competitive research funding, 07680824

Target specificity of dopaminergic neurons in dissociated cultures from the Substantianigra and the ventral tegmental area
Grants-in-Aid for Scientific Research Grant-in-Aid for General Scientific Research (C)
1993 - 1994
MASUKO Sadahiko, FUJIYAMA Fumino, KAWANO Hitoshi, MURATA Yuzo
1.Separate cell cultures of the striatum (ST) and the nucleus accumbens (AC) : After making brain slices, the regions of the ST and the AC were separately dissected from three-day-old postnatal rats. The fragments of brain tissue were dissociated and cultured on a glia feeder layr. Immunohistochemical staining of these cultures revealed that many of cultured neurons were GABAergic. Morphological characteristics of the GABA neurons in the ST culture and in the AC culture were different each other, and were also different from that of the substantia nigra (SN) culture.
2.Tissue specificity of glial effects on the separate cell cultures : Various combination cultures of the separated neurons and glial cells from different brain regions revealed that the SN neurons as well as the ST neurons grew well on glial cell layr prepared from the brain tissue of their own regions or target regions but not on glial cells from non-target areas.
3.Synapse formation between GABA ergic neurons and dopamine (DA) ergic neurons in the separate culture : Electron microscopy using immunohistochemistry for GABA or tyrosine hydroxylase (TH) revealed that synaptic contacts were made reciprocally between GABA ergic and DA ergic neurons in the SN culture. Further study should be made to quantify the synapse formation in various combinations of co-culture, such as in SN-ST culture.
4.Correlation of DA ergic terminals and nitric oxide (NO) neurons in the rat striatum. Electron microscopic study combined with TH immunohistochemistry and NADPH-diaphorase histochemistry demonstrated an association of DA ergic terminal and possible glutamatergic terminals which was directry apposing to the NO neurons, suggesting the site of NMDA receptor-evoked NO release which in turn induce DA release from the DA terminal.
Japan Society for the Promotion of Science, Grant-in-Aid for General Scientific Research (C), Saga Medical School, Coinvestigator not use grants, Competitive research funding, 05680662

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