基底核 Basal Ganglia
P1-2-86 ラット淡蒼球外節と直接路・間接路との関係を形態学的に解析する Innervation of pallidal neurons by a striatal direct and indirect neurons in the rat ○水谷和子1, 苅部冬紀1, 高橋晋1, 雲財知1,2, 藤山文乃1,2 ○Kazuko Mizutani1, Fuyuki Karube1, Susumu Takahashi1, Tomo Unzai1,2, Fumino Fujiyama1,2 同志社大学大学院　脳科学研究科　神経回路形態部門1, CREST, JST2 Lab Neural Circuitry, Grad Sch Brain Sci, Doshisha University, Kyoto1, CREST, JST, Tokyo2 The current model of basal ganglia rests on the idea that the striofugal system is composed of two separate (direct and indirect) pathways originating from distinct cell populations in the striatum. However, striatonigral neurons (striatal direct neurons) give collaterals in the globus pallidus (GPe), which is known as a relay nucleus in the indirect pathway of the basal ganglia (Kawaguchi et al., 1990; Fujiyama et al., 2011). On the other hand, the axonal arborizations of the striatopallidal neurons (striatal indirect pathway neurons) often make two busy arborizations within the GPe, especially in its rostrodorsal and caudoventral portions. The immunohistochemistry also can divide the GPe into three regions: a calcium binding protein calbindin-28K (CB)-rich region bordering to the striatum, a caudomedial CB-rich region, and a CB-poor middle region located between the two CB-rich refions. Our question is how the GPe neurons located in the different regions are involved in the direct or indirect pathways. In the present study, we examined the relationship between the striatal direct/indirect neurons and GPe regions, by using a combination of retrograde labelings of striatonigral and striatopallidal neurons. The results would provide a discussion whether the direct and indirect pathways convey the signals independently or not.	P1-2-87 大脳基底核に発現する細胞接着分子Caspr3の相互作用分子の解析 Interacting molecules of the cell adhesion molecule Caspr3 expressed in the basal ganglia ○平田晴菜1, 梅森十三2,3, 小出剛2, 渡邉和忠1,4, 霜田靖1 ○Haruna Hirata1, Juzoh Umemori2,3, Tsuyoshi Koide2, Kazutada Watanabe1,4, Yasushi Shimoda1 長岡技術科学大学・生物系1, 国立遺伝学研究所・マウス開発研究室2, 藤田保健衛生大学 総合医学研究所・システム医科学研究部門3, 長岡工業高等専門学校4 Dept Bioeng, Nagaoka Univ Tech. Niigata, Japan1, Mouse Genomics Resource Lab, Nat Inst Genetics, Shizuoka, Japan2, Div of Sys Med Sci, ICMS, Fujita Health Univ, Aichi, Japan3, Nagaoka Natl Coll Tech, Nagaoka, Niigata, Japan4 Caspr3 (Contactin associated protein like 3, Cntnap3) is a neural cell adhesion molecule belonging to Caspr family which is composed of five members: Caspr, Caspr2, Caspr3, Caspr4 and Caspr5. It has been demonstrated that Caspr and Caspr2 play essential roles in formation and maintenance of myelinated nerves via interaction with Contactin and TAG-1, respectively. Contactin and TAG-1 compose Contactin family with BIG-1, BIG-2, NB-2 and NB-3. We have recently shown that Caspr3 is expressed during the first to third postnatal weeks in the mouse basal ganglia including the striatum, external segment of the globus pallidus (GPe), subthalamic nucleus (STN), and substantia nigra (SN) and the bundles between the striatum and SN. Caspr3 was expressed in medium spiny neurons (MSNs) in the striatum, but not in dopaminergic neurons in the SN, suggesting that Caspr3 is expressed in MSNs in the direct pathway. However, the molecular mechanism underlying the involvement of Caspr3 in development of the basal ganglia remains unknown. Here, we examined the interaction of Caspr3 with members of Contactin family using HEK293 cells transfected with these molecules. Pull-down assay revealed that Caspr3 interacts with NB-2. We have demonstrated that NB-2 is expressed in the SN in the rat brain (Toyoshima et al., 2009). Then, we examined the expression of NB-2 in the mouse basal ganglia, showing that NB-2 is expressed in striatum, GPe, SN and connection fibers between GPe and SN. In addition, both Caspr3 and NB-2 were expressed in the molecular layer of the dentate gyrus. Our results suggest that interaction between Caspr3 and NB-2 might play important roles in development and function of the basal ganglia. To further analyze function of Caspr3, we are examining the expression of NB-2 in Caspr3 deficit mice.
P1-2-88 線条体ストリオソーム/マトリックスにおけるアンフェタミン連続投与の影響 Long-lasting effect of chronic intermittent methamphetamine treatment on the physiological neural activity of striosome and matrix compartments ○井上律子1, 青崎敏彦1, 三浦正巳1 ○Ritsuko Inoue1, Toshihiko Aosaki1, Masami Miura1 地方独立行政法人東京都健康長寿医療センター研究所1 Neurophysiology, Tokyo Metropolitan Inst of Gerontology, Tokyo, Japan1 The striatum is a major nucleus of the basal ganglia and divided into two compartments, striosomes and the extrastriosomal matrix, which differ in time of neurogenesis, several cytochemical markers, and input-output connections. The striosomes and dopaminergic neurons of substantia nigra pars compacta (SNc) mutually innervate each other. Alteration of dopamine level in the basal ganglia produces neural and behavioral changes. Methamphetamine is a psychostimulant drug which enhances dopamine neurotransmission and increases locomotor activity. Chronic intermittent methamphetamine treatment induces repetitive behavior termed motor stereotypy. In this study, we examined whether the effects of chronic intermittent methamphetamine stimulation on the physiological activity of striatal neurons differ between each of the striatal compartments. To visually identify the striosomes, we used a TH-GFP transgenic mouse strain expressing eGFP in a compartment-specific manner. Methamphetamine (5 mg/kg) or saline was injected intraperitoneally twice daily (at 9:00 and 16:30) for 5 consecutive days. We measured stereotypy scores after the injection in the morning. After withdrawal of 2-5 days, each mouse received a challenge with methamphetamine or saline, and enhanced stereotypy was still induced by the drug challenge. These mice were dissected after 1 hour from the final challenge. Then, we compared Fos expression induced by the challenge following the chronic intermittent methamphetamine treatment and withdrawal between in the striatal compartments. We also made whole-cell recordings from medium spiny neurons in slice preparation taken from the mice treated with amphetamine or saline. We compared miniature excitatory postsynaptic currents (EPSCs) recorded between in the striatal compartments. These studies would help explain the roles of the striosomes in the activity of local neural circuits in striosome/matrix compartments.	P1-2-89 ラット大脳基底核の結合様式を視床下核と皮質領野との関係から検討する Neural connection pattern in the rat basal ganglia, with relation to cortico-subthalamic pathway ○苅部冬紀1, 藤山文乃1,2 ○Fuyuki Karube1, Fumino Fujiyama1,2 同志社大学　脳科学研究科1, CREST, JST, 東京2 Lab Neural Circuitry, Grad Sch Brain Sci, Doshisha University, Kyoto1, CREST, JST, Tokyo2 Cerebral cortex, basal ganglia, and thalamus form a neural circuit loop, which is considered as functionally segregated parallel loops, such as motor loop, limbic loop, and so on. Anatomical and physiological studies revealed topological connection on cortico-striatal and striato-pallidal projections. Subthalamic nucleus (STh) receives inputs from globus pallidus external segment (GPe) and a wide range of cortical area, and in turn projects to substantia nigra (SN) and GPe. It is also reported that pallido-subthalamic and cortico-subthalamic projections are topologically segregated, indicating subdivisions of STh. However, those reported manners of subdivisions are highly variable, and thus further confirmation is necessary to precisely uncover how functionally segregated cortico-basal ganglia loops including STh are organized. To answer this question, we investigated anatomical connections involved in STh, GPe, entopeduncular nucleus, SN, and several cortical areas by antero- and retro-grade neural tracers combined with immunohistochemistry. For cortico-subthalamic pathway, different cortical area tended to project toward distinct position of STh: motor cortex often projected toward rostro-lateral region of STh, whereas limbic related cortical area toward medio-caudal region. Projection from GPe to STh also showed topological difference, caudal STh often received from dorso-rostral GPe, whereas rostral STh from medio-ventral GPe. We also investigated connection between STh and other brain regions, and try to discuss to what extent distinct cortico-basal ganglia loops are separated from each other in rodents.
P1-2-90 ラット線条体ストリオソーム・マトリックス構造における視床正中線核群および髄板内核群単一ニューロン投射の定量的解析 Quantitative analysis of single cell projection from midline and intralaminar thalamic nuclei to striosome and matrix compartments of rat striatum ○雲財知1,2,3, 倉本恵梨子3, 金子武嗣3, 藤山文乃1,2 ○Tomo Unzai1,2,3, Eriko Kuramoto3, Takeshi Kaneko3, Fumino Fujiyama1,2 同志社大院・脳科学・神経回路形態1, 科学技術振興機構戦略的創造研究推進事業2, 京都大院・医・高次脳形態3 Lab Neural Circuitry, Grad Sch Brain Sci, Doshisha Univ, Kyoto1, CREST, JST, Kawaguchi2, Dept Morphol Brain Sci, Univ of Kyoto, Kyoto3 The midline (ML) and the intralaminar (IL) thalamic nuclei are known to be involved in sensory, motor and cognitive functions, and send excitatory input to the striatum and the other areas. The striosome and matrix compartments are mosaic organizations of the striatum and distinguishable from each other by the expression of neurochemical markers and the input-output organizations. To clarify the difference in thalamostriatal projection to the striosome and matrix compartments, we investigated the axonal arborizations of single thalamic neurons of the rat. We combined the single neuron-tracing method with immunohistochemistry, and examined the distribution of thalamostriatal axon varicosities in the striosome and matrix compartments. About a half of the thalamostriatal axon varicosities of the single neurons in the ML are distributed in the striosome compartments. Since the striosome compartments occupy about 11-15% of the total volume in the striatum, these neurons are considered to project preferentially to the striosome compartments. The axonal varicosities of the parafascicular (Pf) thalamic neurons distributed preferentially in the matrix compartment, and the rostral intralaminar (ILr) thalamic neurons didn't show significant preference to the striatal compartments. Most of the neurons also projected to the cerebral cortex. The ML neurons projected preferentially to the limbic cortex. In contrast, IL neurons projected preferentially to the sensorimotor cortex. The striosome and matrix compartments considered to have different connection each other not only with the cerebral cortex but also with the thalamus.	P1-2-91 腹側線条体から背側線条体へのフィードフォワード型ドパミン神経回路の存在 Dopaminergic circuitry from the ventral striatum to the dorsal striatum is an effective feed-forward loop ○池田弘子1,2, 三枝禎2, 亀井淳三1, 越川憲明2 ○Hiroko Ikeda1,2, Tadashi Saigusa2, Junzo Kamei1, Noriaki Koshikawa2, Alexander R Cools3 星薬大・薬物治療1, 日本大・歯・薬理2 Dept Pathophysiol Ther, Hoshi Univ Sch Pharm Pharmaceut1, Dept Pharmacol, Nihon Univ Sch Dent2, Dept Cognitive Neurosci, Radboud Univ Nijmegen3 Central dopamine systems are key players in the cerebral organization of behavior and in various neurological and psychiatric diseases. We demonstrate the presence of a neurochemical feed-forward loop characterized by region-specific changes in dopamine efflux in serially connected striatal regions, providing evidence in favor of the existence of so-called spiraling striato-nigro-striatal connections. Using in vivo microdialysis of rats, we showed that the stimulation of dopamine D1/D2 receptors in the nucleus accumbens shell decreased dorsal striatal dopamine efflux via a feed-forward loop involving the nucleus accumbens shell, core, ventrolateral and dorsal striatum: the injection of a mixture of dopamine D1 receptor agonist SKF 38393 and D2 receptor agonist quinpirole into the nucleus accumbens shell decreased dopamine efflux in the nucleus accumbens core; the inhibition of dopamine D1/D2 receptors by cis-(Z)-flupenthixol in the nucleus accumbens core increased dopamine efflux in the ventrolateral striatum, and the stimulation of dopamine D1/D2 receptors by a mixture of SKF 38393 and quinpirole in the ventrolateral striatum decreased dopamine efflux in the dorsal striatum. Finally, the stimulation of dopamine D1/D2 receptors by a mixture of SKF 38393 and quinpirole in the nucleus accumbens shell decreased dopamine efflux in the dorsal striatum. To examine the functional role of this feed-forward loop, we conducted the behavioral analysis using turning behavior. Unilateral injection of a mixture of SKF 38393 and quinpirole into the nucleus accumbens shell elicited contraversive turning. This contraversive turning was significantly decreased by the inhibition of either dopamine D1 (SCH 23390) or D2 (l-sulpiride) receptors in the ventrolateral striatum. Thus, distinct striatal regions act also in series, providing a better understanding of the neural mechanisms underlying dopamine-dependent behaviors and disorders.
P1-2-92 トランスジェニックラット線条体へのレンチウイルス遺伝子導入によるNR1遺伝子ノックダウンに基づく細胞タイプ選択的なグルタミン酸神経伝達の抑制 Cell type-specific suppression of glutamatergic neurotransmission based on NR1-knockdown by lentiviral vector-mediated gene transfer into the transgenic rat striatum ○松下夏樹1, 松下佐知1, 深堀良二2, 加藤成樹2, 内ヶ島基政3, 渡辺雅彦3, 塩田明4, 上田正次4, 小林和人2, 東山繁樹1,5 ○Natsuki Matsushita1, Sachi Matsushita1, Ryoji Fukabori2, Shigeki Kato2, Motokazu Uchigashima3, Masahiko Watanabe3, Akira Shiota4, Masatsugu Ueda4, Kazuto Kobayashi2, Shigeki Higashiyama1,5 愛媛大・プロテオ医セ1, 福島医大・医・生体機能2, 北大院・医・解剖3, フェニックスバイオ（株）・宇都宮事業所4, 愛媛大院・医5 Ehime Univ Proteo-Medicine Res Ctr, Ehime1, Dept Mol Genet, Inst Biomed Sci, Fukushima Med Univ, Fukushima2, Dept Anat, Hokkaido Univ Grad Sch Med, Sapporo3, Utsunomiya Branch, PhoenixBio, Utsunomiya4, Ehime Univ Grad Sch Med, Ehime5 Short hairpin RNA (shRNA) knockdown vectors have been often used in brain analyses, however, conventional shRNA vectors are not suitable to be applied to a specific cell type, because these vectors produce a knockdown phenotype in all cell types in the transduced areas. A method for cell type-specific knockdown in animals is favorable to investigate gene fucntions in a local neural circuit. We have recently developed lentivirus vectors for conditional knockdown that could be dependent on the Cre/loxP recombination. We have also generated BAC transgenic rat lines expressing Cre recombinase under the control of dopamine D2 receptor (D2R) gene promoter. In this study, we tried D2R neuron-specific suppression of glutamatergic neurotransimission based on the knockdown of NR1 gene in the dorsal striatum using a combination of transgenic rat and lentivirus-mediated gene transfer. The lentiviral vectors were injected into dorsal striatum of the D2R-Cre transgenic rat brains, and analyzed whether the selective NR1-knockdown could be induced in the D2R-neurons. Recombination-dependent appearance of GFP positive cells together with induction of shRNA expression, that is a property of the knockdown vector used in this study, was clearly observed in the striatum. This result suggested the possibility of D2R neuron-specific NR1-knockdown in striatum. We are currently analyzing changes in glutamatergic neurotransmission and behavior of the transgenic rats. The D2R neuron-specific NR1-knockdown developed in this study will be a powerful model for studies on physiological roles of glutamatergic neurotransimission in the striatal indirect pathway of basal ganglia circuits.	P1-2-93 線条体外側部 Calbindin 低発現領域（ V 字型縞構造）の GPR155 発現ニューロン Analysis of Calbindin D28K low-expressing V-shaped stripe in the mouse lateral striatum using GPR155 antibody ○山下雄司1, , 丸山正人1, 加瀬政彦1, 杉本哲夫1 ○Yuji Yamashita1, Stefan Trifonov1, Masato Maruyama1, Masahiko Kase1, Tetsuo Sugimoto1 関西医科大学 医学部 脳構築学1 Dept. Anat. Brain Sci., Kansai Med. Univ., Osaka, Japan1 Integral membrane protein GPR155 is a novel member of the group of proteins containing DEP domain. It is expressed in the mouse striatum, hippocampus and cerebral cortex, and changes in its expression have been related to autism-spectrum disorders and Huntington's disease. Molecular mechanisms associated with the localization and function of GPR155 in the striatum have yet to be elucidated. We have shown that GPR155 in the mouse has splicing variants 1 to 5, in which variant 1 is dominant in the brain [Trifonov et al. Biochem Biophys Res Commun 2010;398:19-25; Eur J Neurosci 2012;35:711-22]. We here demonstrate that the neurons highly expressing the variant 1 are dominantly accumulated in the V-shaped stripe structure in mouse lateral striatum delineated by its low expression of Calbindin D28K. In this study, we have prepared rabbit anti-peptide antibodies against mouse GPR155 and examined its distribution on immunostained tissue sections of mouse striatum. To visualize the V-shaped stripe structure, we have immunostained the tissue sections with Calbindin D28K antibodies. GPR155-heavily immunopositive neurons were found in the lateral striatum largely conforming to the regions of the V-shaped stripe structure visualized by the reduced Calbindin D28K immunoreactivity. GPR155-moderately immunopositive neurons were distributed in the surrounding areas including the central and medial striatal regions. The majority of GPR155-immunopositive cells appeared as medium spiny projection neurons. In the substantia nigra pars reticulata and internal segment of the globus pallidus, immunopositive fibers were accumulated in regions. Taken together with the results from in situ hybridization, GPR155-expressing neurons are regarded as or closely correlated with projection neurons highly expressing GAD1 in the lateral striatum. These projection neurons may contribute to basal ganglia circuits regulating motor execution.
P1-2-94 皮質線条体シナプス可塑性におけるドーパミンの役割 Role of dopamine in corticostriatal synaptic plasticity ○中野高志1 ○Takashi Nakano1, Jeff Wickens1 沖縄科学技術大学院大学1 Okinawa Institute of Science and Technology, Okinawa1 Dopamine neurons in the substantia nigra project to the striatum. The dopamine neurotransmission modulates corticostriatal synaptic plasticity, which is thought to contribute to reinforcement learning. Pulsatile administration of dopamine combined with cortical stimulation and postsynaptic current injection induces long-term potentiation (LTP) of the synapse. Under other conditions, such as the presence of the potassium channel blocker tetraethylammonium (TEA) or magnesium-free extracellular solution, induce LTP by cortical stimulation and postsynaptic current injection even without dopamine administration. We investigated the role of dopamine in these forms of LTP. To cause dopamine release in the striatum, we used an optogenetic approach. AAV5- CAG-ChR2(H134R)-mCherry was injected into the substantia nigra. Mice were allowed to recover for at least 3 weeks before further procedures. A lightsource (LED) was direced through the objective lens to evoke dopamine release in the striatum, which was measured using fast scan cyclic voltammetry. We found that pulsatile dopamine was evoked by a short light pulse in the striatum, at concentrations sufficient to induce dopamine dependent LTP. LTP was also induced by combined cortical and postsynaptic action potentials in magnesium-free solution. In magnesium-free solution, dopamine responses to optical stimulation were prolonged. Extracellular TEA, which promoted LTP, also enhanced the amplitude of dopamine response to optical stimulation. Furthermore, spontaneous dopamine release occurred in the presence of extracellular TEA. These findings suggest that in both Mg-free and TEA forms of LTP, facilitated dopamine release plays a key role.	P1-2-95 ラット淡蒼球外節の投射様式を領域ごとに解析する Regional Difference in Network between the Striatum and Globus Pallidus ○藤山文乃1,2, 中野隆4, 松田和郎4, 呉胤美1, 水谷和子1, 古田隆寛3, 苅部冬紀1, 高橋晋1, 雲財知1, 宇田川潤4, 金子武嗣3 ○Fumino Fujiyama1,2, Takashi Nakano4, Wakoto Matsuda4, Yoon Mi Oh1, Kazuko Mizutani1, Takahiro Furuta3, Fuyuki Karube1, Susumu Takahashi1, Tomo Unzai1, Jun Udagawa4, Takeshi Kaneko3 同志社大学大学院　脳科学研究科　神経回路形態部門1, 京都大学3, 滋賀医科大学4 Lab Neural Circuitry, Grad Sch Brain Sci, Doshisha University, Kyoto1, CREST, JST, Tokyo2, Kyoto University, Kyoto3, Shiga University of Medical Science, Shiga4 The globus pallidus (GPe) is known as a relay nucleus in the indirect pathway of the basal ganglia. However, GPe neurons which project to the neostriatum solely (pallidostriatal neurons) have been reported in rats (Mallet et al., 2012) and primates (Sato et al., 2000). Recently, we found that not only the striatopallidal neurons (striatal indirect pathway neurons) but also the striatonigral neurons (striatal direct neurons) give collaterals in the GPe (Kawaguchi et al., 1990; Fujiyama et al., 2011) and the targeted region in GPe were different between the striatal direct and indirect pathway neurons. To put up the candidates for the neurons involved in the feedback recurrent loop which composed of the striatal neurons, we investigated the axonal trajectry of the GPe neurons in the different regions in rats by labeling the processes with Biotin Dextran Amine and Sindbis viruses expressing membrane-targeted fluorescent protein. When we divided the GPe into rostrodorsal, centromedial and caudoventral parts, pallidostriatal neurons were preferentially located in the rostrodorsal parts in GPe. These results suggest that the GPe is functionally segregated into rostrodorsal and the other parts, and that the rostrodorsal parts may participate in the in the feedback recurrent loop in the basal ganglia.
P1-2-96 線条体-淡蒼球シナプスの反復刺激は短期可塑的変化を誘導する Repetitive activation on Striato-Pallidal inhibitory synapses elicits short-term plasticity ○金主賢1,2, 喜多均2 ○Juhyon Kim1,2, Hitoshi Kita2 富山大学　工学部　生体情報1, テネシー大学　米国2 Div. of Bio-Information Eng., University of Toyama1, Dept. of Anatomy and Neurobiology, College of Medicine, The University of Tennessee Health Science Center, USA2 The cortico-striato (Str)-globus pallidus external segment (GPe) projection plays major roles in the control of neuronal activity in the basal ganglia under both normal and pathological conditions. Striatal projection neurons fire with very different frequency and patterns depending on the condition of the animal. Unit recordings in rodents and monkeys showed that most Str projection neurons were quiescent or only fired occasionally when animals were at rest. In task-performing animals, most behavioral-related unit activities occur as a train of firing lasting from 100 ms to over 1 s, with a maximum frequency of 100 Hz. These diverse activity patterns should alter the efficacy of the Str-GPe synapses. However, studies on the plasticity of Str-GPe synapses are scarce. The present study used rat brain slice preparations to address our hypothesis that the gain of this disynaptic projection is dynamically controlled by activations of short-term plasticity mechanisms of Str-GPe synapses. The results show that the Str-GPe synapses have very strong short-term enhancement mechanisms and that repetitive burst activation of the Str-GPe synapses, which mimic oscillatory burst firing of Str neurons, can sustain enhanced states of synaptic transmission for tens of seconds. The results reveal that the short-term enhancement of Str-GPe synapses contributes to the generation of pauses in the firing of GPe neurons and that signal transfer function in the Str-GPe projection is highly dependent on the firing pattern of Str neurons.	P1-2-97 中脳における非ドパミン神経細胞の投射様式 Axonal arborization of midbrain non-dopaminergic neurons: single-cell study ○松田和郎1, 古田貴寛1, 倉本恵梨子1, 日置寛之1, 藤山文乃1,2, 金子武嗣1 ○Wakoto Matsuda1, Takahiro Furuta1, Eriko Kuramoto1, Hiroyuki Hioki1, Fumino Fujiyama1,2, Takeshi Kaneko1 京都大院・医・高次脳形態1, 同志社大院　脳科学　神経回路2 Dept Morphol Brain Sci, Grad Sch of Med, Kyoto Univ, Kyoto1, Lab of Neural Circuitry, Grad Sch of Brain Sci, Doshisha Univ2 Neurons in the substantia nigra compacta (SNc) and ventral tegmental area (VTA) mediate a variety of brain functions, such as motor control, emotion, and reward. We studied the axonal arborization of VTA and SNc non-dopaminergic neurons with Sindbis virus vectors that coded membrane-targeted green fluorescent protein (GFP). After injections of the viral vectors in the rat VTA or SNc, the infected neurons were examined whether or not they were immunoreactive for tyrosine hydroxylase, and labeled by the immunoperoxidase method with an anti-GFP antibody. After the reconstruction of projection axons, some neurons were observed to project their axons to the lateral hypothalamic area, thalamus, and preoptic area. Many of these non-dopaminergic neurons were observed to form sparse bushes in their terminal fields, whereas those of dopaminergic ones to form high-dens bushes. Additionaly, the labeled fibers of non-dopaminergic neurons possessed many voluminous varicosities, whereas those of dopaminergic neurons possessed ambiguous ones. Thus, the present study revealed a difference in the axonal ramifications of single non-dopaminergic neurons compared with dopaminergic ones.
P1-2-98 近接した直接路・間接路ニューロンの線条体から淡蒼球外節への軸索投射様式の解析 Projections of the adjacent direct and indirect neostriatal neurons to the external globus pallidus ○岡本慎一郎1, 日置寛之1, 孫在隣1, 金子武嗣1 ○Shinichiro Okamoto1, Hiroyuki Hioki1, Jaerin Sohn1, Takeshi Kaneko1 京都大学大学院 医学研究科 高次脳形態学1 Dept Morphol Brain Sci, Grad Sch of Med, Kyoto Univ, Kyoto, Japan1 The neostriatum, input nuclei of the basal ganglia, plays a key role in motor control and cognitive function. The medium-sized spiny neurons (MSNs) constitute over 90% of the neostriatal neurons and can be divided in two different subtypes as direct or indirect pathway neurons. The direct pathway neurons express dopamine D1 receptor and project to the substantia nigra reticulata (SNr), entopeduncular nucleus (EP) and external globus pallidus (GPe) (Fujiyama et al., 2012). In contrast, indirect pathway neurons are characterized by the expression of D2 receptor and innervate the GPe only. It is unclear how these adjacent neurons, which are presumed to be received same inputs, send the axon fibers to the targeting nuclei, especially to GPe.To visualize the axons of MSNs, we used transgenic mice and adeno-associated virus (AAV). The transgenic mice express Cre recombinase only in the D1- or D2-expressing neurons and AAV produced GFP in Cre-positive cells and tdTomato in negative cells. Thus, after injection of the viral vector into the neostriatum of the transgenic mice, the axon fibers of D1 and D2 neurons are separately labeled with these fluorescent proteins.The indirect pathway MSNs formed two bushy arborizations in the edge of the GPe, while the direct pathway neurons projected to the middle part of the GPe. SNr and EP receive inputs from only directly neurons, not indirectly cells. We found that the long projection fibers from injected sites to the GPe in the same sagittal section. It seems that the MSNs located in the lateral part of CPu send axons to the lateral part of GPe, and the ones in medial part innervated to medial part of the GPe. Subsequently, we will analyze the distribution of the axon terminals in not only GPe but also EP and SNr with 3D-reconstructed data in more detail.	P1-2-99 即時的な行動選択に関わる淡蒼球外節の神経活動 Neuronal Activity during Rapid Action Selection in the Primate Globus Pallidus External Segment ○吉田篤司1, 田中真樹1 ○Atsushi Yoshida1, Masaki Tanaka1 北海道大学医学研究科神経生理学分野1 Departments of Physiology, Hokkaido University School of Medicine, Sapporo1 We choose an action deliberately or in urgent need. Although evidence indicates that the basal ganglia are involved in the deliberate control of action selection, the underlying neural mechanism for rapid decision making remains unknown. The antisaccade task, which requires the subjects to generate saccades away from the visual stimulus, has long been used to investigate the underlying neural mechanism of action selection. Previously we found that the gloubus pallidus external segment (GPe) plays a role in the generation of antisaccades when the task rule was given by color of the fixation point in advance of the target appearance (Deliberate condition). To elucidate a role in the rapid action selection, we devised a task in which the task rule (antisaccade, prosaccade, NoGo) was indicated by color of the target (Immediate condition) , and compared neuronal activity in the GPe between the conditions. Consistent with our previous study, two types of neurons were found. Approximately 63% neurons (n = 79) increased their firing rates during saccades, while the remaining neurons (n = 46) decreased. In the Deliberate condition, both types of neurons exhibited greater firing modulation during antisaccades than during the other two tasks. On the other hand, in the Immediate condition, neuronal activity during prosaccades was comparable to that during antisaccades for both types of neurons, suggesting the involvement of the GPe in the generation of prosaccades. We also found that the activity of the decrease-type neurons exhibited similar time course between the NoGo and the antisaccade trials, whereas the increase-type neurons exhibited greater firing modulation during antisaccades than during the NoGo trial. These results suggest that the GPe might be involved in the rapid action selection and that different pathways might have different roles. Different contributions depending on the tasks could be critically tested by pharmacological application to the recording sites.
P1-2-100 Differential influence of subthalamic nucleus and substantia nigra pars reticulata electrical stimulation on spontaneous and purposive saccades ○Jay J. Jantz1, Masayuki Watanabe1, Ron Levy1, Douglas P. Munoz1 Centre for Neuroscience Studies, Queen's University, Kingston, Canada1 In the basal ganglia (BG), the 'indirect' and 'hyperdirect' inhibitory pathways converge in the subthalamic nucleus (STN), which then influences the substantia nigra pars reticulata (SNr; BG output structure). We investigated whether the STN is involved in both spontaneous and purposive saccade initiation, and if so, through what BG pathway. We paired sub-threshold electrical stimulation of the STN or SNr in rhesus monkeys with a behavioral examination of saccadic eye movements. If STN and SNr stimulation effects are similar, then the STN likely mediates saccade initiation through the glutamatergic STN-SNr pathway. Otherwise, the STN may mediate saccade initiation through an alternate path. Two monkeys performed the following paradigms: (1) view a blank screen freely (spontaneous task), (2) generate a saccade (2) toward (pro-saccade) or (3) away from (anti-saccade) a peripheral visual stimulus. Sub-threshold stimulation in STN in the spontaneous task produced a bias of saccades toward the contralateral hemifield with respect to stimulation site, whereas stimulation of the SNr produced an ipsilateral bias of saccades. Stimulation in either the STN or SNr during pro- and anti-saccade tasks either prolonged reaction times for saccades bilaterally, or contralateral to the stimulation site. Opposite behavioral effects of STN and SNr stimulation during the spontaneous task challenge the glutamatergic STN-SNr pathway for saccade initiation in this task. However, similarities between STN and SNr stimulation effects in the pro- and anti-saccade tasks suggest that the STN is involved in a task-dependent modulation of saccade initiation, through multiple pathways depending on cognitive demand.	P1-2-101 Electrophysiological properties of midbrain dopamine neurons in the spontaneously hypertensive and wistar-kyoto rat strains ○Kyoko Tossell1, Tim J. Aitman1, Mark A. Ungless1 MRC Clinical Sciences Centre, Imperial College London, Faculty of Medicine, UK1 The spontaneously hypertensive rat (SHR) has been used extensively to identify genes underlying a number of metabolic phenotypes. In addition, these rats are hyperactive and impulsive, and it has been suggested represent a model of attention-deficit hyperactivity disorder (ADHD). These behavioural features, and ADHD, are commonly associated with dysfunction of the dopamine system. However, little is known about dopamine neuron properties in SHRs (or in control wistar-kyoto rats (WKYRs)). We have, therefore, conducted whole-cell electrophysiological recordings from midbrain dopamine neurons in acute brain slices from these two rat strains, combined with single-cell-labelling for immunohistochemical identification and anatomical reconstruction. Spontaneous firing activity, action potential waveform characteristics, and maximal firing rate in response to depolarisation, were all similar in both strains. In addition, excitatory glutamatergic synaptic activity appeared similar in both strains. However, we observed significantly lower amplitude and frequency of miniature inhibitory GABAergic synaptic currents (mIPSCs) in SHRs compared to WKYRs. Evoked IPSC paired-pulse ratios and the coefficient of variation of evoked IPSC amplitude were the same in both strains, suggesting that there are no differences in presynaptic GABA-release, and that the differences we observed in mIPSC frequency and amplitude may be postsynaptic. Taken together, these findings suggest that GABAergic inhibition of dopamine neurons is reduced in SHRs, which may in turn lead to dopaminergic hyperactivity, and consequently behavioural hyperactivity.

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