てんかん、頭痛、めまい Epilepsy, Headache, Vertigo
P1-2-198 ピロカルピン誘発性てんかんによるBRINPファミリーの発現変化 Alteration of BRINP family expression in hippocampus by pilocarpine-induced seizures ○越智大輔1, 小林三和子1, 松岡一郎1 ○Daisuke Ochi1, Miwako Kobayashi1, Ichiro Matsuoka1 松山大学薬学部生理化学研究室1 Col. Pharm. Sci., Matsuyama Univ., Matsuyama, Japan1 We have previously reported that BRINP family genes are expressed in developing as well as adult mouse brain. Among the three family members, BRINP1 is most highly expressed in various brain regions including hippocampus in adult mouse. BRINP1 expression in adult hippocampus is further up-regulated by the intraperitoneal (i.p.) administration of kainic acid (KA), a glutamatergic agonist, in a similar manner to BDNF expression. Furthermore BRINP1-KO mice showed abnormal behaviors such as increased motility, poor social interaction and loss of concentration. These results suggest that induced BRINP1 acts on modulation of hippocampal neuronal circuitry associated with psychiatric disorder-like behavior.In the present study, to elucidate physiological roles of BRINP1 in hippocampus we examined BRINP family expression in pilocarpine-induced seizure model mouse. Pilocarpine, a cholinergic agonist, stimulates muscarinic acetylcholine receptor which is highly expressed in hippocampus and is known to cause mossy fiber sprouting. We administered pilocarpine (380 mg/kg, i.p.) to male C57BL/6J mice after pretreatment with scopolamine (9 mg/kg, i.p.) to minimize peripheral effect. After observation of continuous tonic/chronic convulsion in mice, diazepam (10 mg/kg, i.p.) was administered to terminate seizure. Six hours after pilocarpine injection, mice were sacrificed and brain samples were dissected. Expression levels of mRNA of BRINPs (BRINP1, 2, 3), BDNF and GAPDH were determined by qRT-PCR using total RNA from hippocampus. We found that 2-fold increase in BRINP1-mRNA and 3-fold increase in BDNF-mRNA by pilocarpine treatment. BRINP2 was slightly increased but there was no change in BRINP3 expression. Induction of BRINP1 by both glutamatergic (KA) and cholinergic (pilocarpine) agonists suggest that BRINP1 acts extensively in various excitatory neurons in hippocampus to modulate behavioral associated brain function.	P1-2-199 皮質拡延性抑制におけるグルタミン酸輸送体の役割 Role of the glutamate transporters in the cortical spreading depression ○孫偉楠1, 伊藤享子1, 相田知海1, 柳澤美智子1, 田中光一1, 相澤秀紀1 ○Weinan Sun1, Yukiko Itou1, Tomomi Aida1, Michiko Yanagisawa1, Kohichi Tanaka1, Hidenori Aizawa1 東京医歯大・難治研・分子神経1 Dept of Mol Neurosci, Sch of Biomed Sci, Med Res Inst and Cent Brain Int Res, Tokyo Med & Dent Univ, Tokyo1 Spreading depression (SD) is a propagating wave of the depolarization in the neuronal and glial cells. Recent studies showed that cortical SD is associated with the stroke and migraine aura, suggesting that excessive excitability of the brain underlies the pathophysiology of these diseases. Despite of a surge of interest in SD, molecular mechanism which regulates SD remains unclear. Previous studies indicated that glutamate in the extracellular space plays critical roles in propagation of SD in the cortex, since the glutamate receptor antagonist impairs SD propagation. It is also known that extracellular glutamate concentration is primarily regulated by glutamate transporters. Therefore, we hypothesized that sensitivity to the cortical SD might be under the influence of glutamate transporter(s). To address how the glutamate transporters influence the SD propagation in vivo, we generated conditional knockout mouse GFAP-Cre(+/-); GLT-1(flox/flox) in which the glial glutamate transporter GLT-1 was defective. Conditional knockout mice survived longer than GLT-1 null mice, majority of which died of severe seizure. SD was induced by local application of potassium chloride in the cerebral cortex of the anesthetized mouse. Electrophysiological recording of cortical SD revealed that the GLT-1 mutants tended to show shorter latency until the first SD, faster velocity and larger number of SD within an hour than the control mice. We did not find any changes in the velocity or the number of SD in the mutants lacking the other types of glutamate transporters such as GLAST and EAAC1. These results suggest that, among transporters expressed in CNS, GLT1 plays a critical role in modulating cortical SD associated with stroke and migraine aura. Examining the inhibitory effect of GLT1 activation on SD may provide a clue to develop a novel treatment for these diseases with abnormality in the neuronal excitability.
P1-2-200 ドーパミン作動性ニューロンが重積てんかん発作後のクロマチン再構築に及ぼす影響 Effects of dopaminergic system on chromatin remodeling in neurons after status epilepticus ○森徹自1, 若林毅俊1, 平原幸恵1, 高森康晴1, 小池太郎1, 山田久夫1 ○Tetsuji Mori1, Taketoshi Wakabayashi1, Yukie Hirahara1, Yasuharu Takamori1, Tarou Koike1, Hisao Yamada1 関西医科大学　解剖学第一講座1 Dept. Anatomy and Cell Science, Kansai Medical Univ., Osaka1 Abnormal neuronal excitation, stress, and drug abuse induce chromatin modification in neurons leading to regulation of gene expression. It is known that chromatin modification occurs in neurons of the hippocampus after status epilepticus (SE). In the previous meeting, we reported that SE significantly upregulates chromatin modification in neurons outside of the hippocampus with histochemical technique using anti-phosphorylated histone H3 (PH3) antibody. In this study, we analyzed detailed distribution pattern of PH3+ neurons after SE. The most prominent upregulation of H3 phosphorylation was detected in the caudate putamen (CPu), nucleus accumbens, and moderate upregulation was detected several regions including upper and lower layer of the cerebral cortex. Especially in the CPu, there was a density gradient of PH3+ neuron. Next, we analyzed a signaling pathway leading to H3 phosphorylation. Because many studies suggest that dopamine receptors activate MAPK-MSK1 (mitogen- and stress-activated protein kinase 1) pathway and result in H3 phosphorylation, we compared the distribution pattern of p-MSK1 and PH3 in the SE brain. We found that distribution regions overlapped, but p-MSK1+ neurons distributed more restricted regions than PH3+ neurons. Furthermore, after unilateral ablation of dopaminergic neurons projection to the CPu, distribution of PH3+ neurons changed in the CPu. These results suggest that H3 phosphorylation in the CPu after SE can be induced other than the dopamine receptor system.	P1-2-201 側頭葉てんかんにおける神経機能結合変化 Altered functional connectivity in patients with temporal lobe epilepsy ○谷直樹1, 貴島晴彦1, クーウィ ミン1, 押野悟1, 園尾知之1, 細見晃一1, 柳澤琢史3, 平田雅之1, 吉峰俊樹1 ○Naoki Tani1, Haruhiko Kishima1, Hui Ming Khoo1, Satoru Oshino1, Tomoyuki Maruo1, Koichi Hosomi1, Takufumi Yanagisawa3, Masayuki Hirata1, Toshiki Yoshimine1 大阪大学医学部脳神経外科1, 大手前病院　脳神経外科2, 大阪大学大学院　医学系研究科　保健学専攻3 Department of Neurosrugery, Osaka University Medical School, Osaka1, Department of Neurosurgery, Otemae Hospital, Osaka, Japan2, Osaka University Graduate School of Medicine, Division of Health Sciences3 Functional connectivity refers to the temporal correlation between remote neurophysiological events in the distributed neural areas. Currently, the functional connectivity in the resting brain, also known as the default mode network (DMN), is one of the most well-studied network of the brain. This network may represent the underlying physiological processes related to the baseline integrated function of the brain. Changes in the DMN are reported in patients with some neuropsychological disorders. The present study is aimed to investigate changes in the resting state network in the brain of temporal lobe epilepsy patients.Six patients with right medial temporal lobe epilepsy (mTLE) and 7 healthy volunteers are included in this study. These patients suffered a long history of seizure, and three of six right mTLE patients showed memory impairment. BOLD images at resting state were obtained with 3T MRI. Correlation coefficients between about 100 ROIs were calculated to identify the DMN.In comparison with healthy controls, mTLE patients showed significantly decreased connectivity between regions within the temporal lobe, and between the medial temporal regions of both hemispheres. On the contrary, the connectivity between anterior cingulate and the preftontal regions were significantly increased. Furthermore, patients with memory impairment showed decreased connectivity between anterior DMN and posterior DMN, in comparison with patients with normal memory.The present results suggest that patients with mTLE, especially those who suffered a rather long history of seizure may demonstrate peculiar changes in the functional brain connectivity at rest (DMN). The possibility of the presence of correlation between those changes and the baseline integrated functions of the brain, such as emotional or neuropsychological activities, needs further investigation
P1-2-202 レーザースペックル脳血流計（LSF）を用いたてんかんモデルにおける経時的脳機能解析 Analysis of brain function and blood flow in epileptic rats using Laser speckle flowmetry ○圓尾知之1, 貴島晴彦1, 押野悟1, 中村元1, 谷直樹1,2吉峰俊樹1 ○Tomoyuki Maruo1, Haruhiko Kishima1, Satoru Oshino1, Hajime Nakamura1, Naoki Tani1,2, Hui Ming Khoo1, Toshiki Yoshimine1 大阪大学大学院　医学系研究科　脳神経外科1, 大手前病院　脳神経外科2 Department of Neurosurgery, Osaka University Graduate school of Medicine, Osaka1, Department of Neurosurgery, Otemae Hospital, Osaka2 Objectives: Real-time investigation of cerebral blood flow (CBF) dynamics using single photon emission computed tomography (SPECT) and positron emission tomography (PET) in the diagnosis of epilepsy has been difficult because of constraints of temporal and spatial resolution. Electroencephalography (EEG) and laser speckle flowmetry (LSF) provides information about electrical activity and regional cerebral blood flow respectively in epilepsy. We used an epileptic rat model created by the intra-hippocampal injection of kainic acid (KA) that enabled us to investigate the relationship between EEG and CBF using LSF, thus allowing the continuous imaging of the spatiotemporal dynamics of CBF changes in rats from the inter-ictal to ictal period. Methods: Wistar rats anesthetized with sevoflurane were injected with 1.0 μg/kg KA into the unilateral hippocampus (CA3) after stereotactic implantation of a guide cannula. We measured simultaneous prolonged EEG and CBF using LSF in a rat model with kainic acid (KA)-induced limbic status epilepticus while simultaneous monitoring percutaneous oxygen saturation levels. Results: All rats treated with KA developed a limbic motor seizure status epilepticus 60-120 minutes after KA injection. We observed that CBF had decreased temporarily before the onset of generalized seizures, and that CBF had dynamically increased after generalized seizures. We found waves of depolarization associated changes in local CBF and that a deflection of DC potential repeatedly appeared concomitantly with depression of EEG around the epileptogenic zone. Conclusion: LSF is useful to assess the changes in CBF that are related to neural activity, and the mechanisms of generalized seizures, with high temporal and spatial resolution.	P1-2-203 fosB欠損マウスは成体海馬の神経新生の異常とてんかんの自然発症・うつ様行動を示す fosB-null mice display impaired adult hippocampal neurogenesis and spontaneous epilepsy with depressive behavior ○湯通堂紀子1, 鎌田崇嗣2, 梶谷康介1, 能丸寛子1, 加藤木敦央1, 大西陽子1, 大西克典1, 高瀬敬一郎2, 作見邦彦1, 重藤寛史2, 中別府雄作1 ○Noriko Yutsudo1, Takashi Kamada2, Kosuke Kajitani1, Hiroko Nomaru1, Atsuhisa Katogi1, Yoko H. Ohnishi1, Yoshinori N. Ohnishi1, Kei-ichiro Takase2, Kunihiko Sakumi1, Hiroshi Shigeto2, Yusaku Nakabeppu1 九州大・生体防御医学研究所・脳機能制御学1, 九州大院・医・神経内科2 Neurofunc Genomics, Med Inst Bioreg, Kyushu Univ, Fukuoka, Japan1, Dept Neurol, Kyushu Univ, Fukuoka, Japan2 Patients with epilepsy are at high risk for major depression relative to the general population, and both disorders are associated with changes in adult hippocampal neurogenesis, although the mechanisms underlying disease onset remain unknown. The expression of ΔFosB protein, an alternative splice product of the immediate early gene fosB is known to be induced in neural progenitor cells within the subventricular zone of the lateral ventricles and subgranular zone of the hippocampus following transient forebrain ischemia in the rat brain, and adenovirus-mediated ΔFosB expression can promote neural stem cell proliferation. We recently found that fosB-null mice show increased depressive-like behaviors, thus suggesting impaired neurogenesis in fosB-null mice. We analyzed neurogenesis in the hippocampal dentate gyrus of fosB-null and fosBd/d mice expressing ΔFosB but not FosB, the other alternative splice product of the fosB gene, in comparison with wild-type mice using stereological counting methods, as well as neuropathology, behaviors and gene expression profiles. fosB-null mice but not fosBd/d mice displayed impaired neurogenesis in the adult hippocampus and spontaneous epilepsy. Microarray analysis revealed that genes related to neurogenesis, depression and epilepsy are altered in the hippocampus of fosB-null mice. We therefore concluded that the fosB-null mouse is the first animal model providing a genetic and molecular basis for the comorbidity between depression and epilepsy with abnormal neurogenesis, all of which are caused by loss of a single gene, fosB.
P1-2-204 ラット海馬スライスにおける脱抑制誘導てんかん波の比較 Disinhibition-induced epileptic discharges in rat hippocampal slices ○澤田豊宏1, 夏目季代久1 ○Toyohiro Sawada1, Kiyohisa Natsume1 九州工業大学大学院 生命体工学研究科1 Japan1 The hippocampus has the pathological epileptic discharges. The discharges are induced by the synchronization of the hippocampal pyramidal neurons. They are induced with the application of GABAA receptor antagonist. There are two types of ictal and interictal discharge. Our previous work indicated one of the antagonists picrotoxin (PTX) induced the epileptic discharges. The interictal discharges were induced with the low concentration, and the ictal discharges were high one. In the present study we have confirmed the suggestion using another GABAA receptor antagonist bicuculline (BIC). The experiments were carried out in compliance with the Guide for the Care and Use of Laboratory Animals at Kyushu Institute of Technology. The present data were obtained from 39 hippocampal slices (450-μm thick) of 5 male Wistar rats. The recording glass electrode (<2 MΩ) was placed in the CA3 stratum pyramidale to record the epileptic discharges induced with the application of between 0.1 and 20 μM BIC. The discharges were induced with BIC above 1 μM, 0.1 μM could not induce. The interictal discharges were mainly induced between 1 and 10 μM, while they were not always induced by 20 μM BIC. The ictal discharges were induced in one out of three slices applied by 1 μM BIC. They were induced in all slices by BIC above 5 μM. The frequency, amplitude, inter-burst interval and duration of the interictal and ictal discharges are similar to those of them with the application of PTX, while they more often depended on the concentration. These results suggest that disinhibition can induce the ictal discharges. Hippocampus also has β rhythm. Beta rhythm can be induced in rat hippocampal slices with the application of the cholinergic agent carbachol. Our previous study found that the β oscillation was not affected with the application of PTX in a concentration which induced the epileptic discharges. We will present the results of the experiment replacing PTX with BIC in the poster.	P1-2-205 cephalic aurasを伴うてんかん症例に関する脳波LORETA解析によるKurtosis及びfunctional connectivityの検討 Kurtosis and functional connectivity analysis by EEG sLORETA analysis in an epilepsy patient with cephalic auras ○畑真弘1, 石井良平1, 池田俊一郎1, 青木保典1, 岩瀬真生1武田雅俊1 ○Masahiro Hata1, Ryouhei Ishii1, Shunichiro Ikeda1, Yasunori Aoki1, Masao Iwase1, Roberto D. Pascual-Marqui2,3, Masatoshi Takeda1 大阪大学大学院医学系研究科精神医学教室1, 滋賀医科大学地域精神医療学講座2 Department of Psychiatry, Osaka University, Osaka1, Department of Community Psychiatric Medicine, Shiga University of Medical Science, Shiga2, The KEY Institute for Brain-Mind Research, University Hospital of Psychiatry, Zurich3 A cephalic aura is quite rare in the entire sensory seizure event, although it is common sensory aura especially in frontal lobe seizures. A case reported here was suffered from cephalic aura as a non-vertiginous sense of head movement lasting 2-3 seconds. The aim of this study is to examine the physiological feature of a 41-year old male patient with cephalic auras, whose epileptic origin was estimated to be the left supplementary motor area in our previous study by using magnetoencephalography (MEG) (Canuet et al, Epilepsy Behav, 13:570-574, 2008). This time, we analyzed the scalp EEG data by using sLORETA with current source density (CSD) analysis and functional connectivity analysis in several frequency bands (delta: 2-4Hz, theta: 4.5-7.5Hz, alpha: 8-13Hz, beta: 13.5-30Hz, gamma: 30.5-60Hz, whole band: 2-60Hz) and compared the results with age-matched 20 healthy controls. In addition, we investigated epileptic discharges by sLORETA kurtosis. CSD of this patient was significantly higher than that of healthy group in theta bands at medial frontal gyrus (P<0.01). We also found the functional connectivity significantly more reduced in beta bands between the left transverse temporal gyrus and the left inferior parietal lobule than that of healthy group (P<0.01). The results of kurtosis analysis by sLORETA showed that the origin of spike activities was considered to be the left supplementary motor area which was agreed with the previous MEG study of the same patient. We revealed the physiological feature of CSD, functional connectivity, and spike activities in this patient by sLORETA analysis. We suggest that sLORETA analysis might be able to be applied as clinical evaluation of epilepsy patients.
P1-2-206 大脳皮質スライスてんかん発射活動に伴うERK1/2活性化 ーNMDA・非NMDA受容体の役割 Both NMDA- and non-NMDA-receptors are necessary for ERK1/2 activation by seizure activity in cortical slices ○山肩葉子1,2, 兼子幸一3, 加勢大輔1, 石原博美1小幡邦彦6, 井本敬二1,2 ○Yoko Yamagata1,2, Koichi Kaneko3, Daisuke Kase1, Hiromi Ishihara1, Angus C Nairn4,5, Kunihiko Obata6, Keiji Imoto1,2 生理研・神経シグナル1, 総研大2, 鳥取大・医・精神行動3, Yale大学4, Rockefeller大学5, 生理研・神経化学6 Natl Inst for Physiol Sci, Okazaki, Japan1, SOKENDAI, Okazaki, Japan2, Tottori Univ Grad Sch Med, Yonago, Japan3, Yale Univ, New Haven, USA4, Rockefeller Univ, New York, USA5, Natl Inst for Physiol Sci, Okazaki, Japan6 Extracellular signal-regulated kinase 1/2 (ERK1/2) that belongs to a subfamily of mitogen-activated protein kinases (MAPKs) plays diverse roles in the central nervous system. Activation of ERK1/2 has been observed in various types of neuronal excitation, including seizure activity in vivo and in vitro, as well as in NMDA-receptor (NMDA-R)-dependent long-term potentiation in the hippocampus. We previously showed in cortical slice preparations that NMDA-R-dependent seizure activity introduced by Mg2+-free condition alone did not cause ERK1/2 activation, while inclusion of picrotoxin in Mg2+-free medium to concurrently suppress GABAA-receptor-mediated inhibition caused profound activation of ERK1/2, the condition of which was accompanied by prolonged membrane depolarization and enhanced burst action potential firings. In the present study, we examined the distribution of phospho-ERK1/2, the active form, within the cortical layers, and whether NMDA-R activation is indeed critical for ERK1/2 activation in the latter epileptic condition. Immunohistochemical examination revealed strong phospho-ERK1/2-staining in the superficial and deep cortical layer neurons. When D-APV (50 μM), an NMDA-R antagonist, was included in Mg2+-free medium along with picrotoxin, the level of ERK1/2 activation was significantly reduced compared to that without D-APV. Inclusion of CNQX (10 μM), a non-NMDA-R antagonist, instead of D-APV also caused a similar reduction. These results showed that ERK1/2 activation observed in Mg2+-free condition with picrotoxin was dependent on both NMDA-R and non-NMDA-R activation. Our results indicate that moderate stimulation of synaptic NMDA-Rs is not enough, but profound glutamatergic excitation that involves both NMDA-R and non-NMDA-R activation is necessary for robust ERK1/2 activation to occur at a cortical network level.	P1-2-207 Neuritinは海馬顆粒細胞における神経活動依存的な軸索分枝の形成を誘導する Neuritin induces activity-dependent axonal branching in hippocampal granule cells ○島田忠之1, 吉田知之2, 山形要人1 ○Tadayuki Shimada1, Tomoyuki Yoshida2, Kanato Yamagata1 （公財）都医学研1, 東京大院・医・分子神経生物学2 Neural Plasticity Project, Tokyo Metropolitan Institute of Medical Science, Tokyo1, Department of Molecular Neurobiology and Pharmacology, Graduate School of Medicine, University of Tokyo2 Aberrant sprouting of granule cell axons (mossy fiber) is observed in the dentate gyrus of many patients with temporal lobe epilepsy and in different laboratory animal models of epilepsy. To elucidate the molecular mechanism underlying mossy fiber sprouting in the epileptic hippocampus, we screened activity-regulated genes in the hippocampus, and found that neuritin (also known as candidate plasticity gene 15) expression was rapidly up-regulated after electroconvulsive seizures. Neuritin has also been shown to be inducible in the hippocampus by kainic acid treatment. To investigate whether neuritin induces mossy fiber sprouting, we first overexpressed neuritin in the cultured hippocampal dentate gyrus granule cells. Overexpression of neuritin increased the number and total length of axonal branches but did not alter axonal length. Application of purified neuritin protein also enhanced axonal branch formation and branch elongation in the cultured granule cells. Moreover, overexpression of neuritin resulted in an increase in axonal branch length of the granule cells in organotypic hippocampal slice culture. These results suggest that neuritin induction by epileptic seizures triggers aberrant axonal sprouting in the dentate gyrus granule cells. We are currently investigating how neuritin regulates axonal branching in hippocampal granule cells.
P1-2-208 日本の良性成人型家族性ミオクローヌスてんかんの臨床的表現促進現象 Clinical anticipation of benign adult familial myoclonus epilepsy in Japan ○人見健文1, 小林勝哉2, 近藤孝之2, 松本理器2, 高橋良輔2, 池田昭夫2 ○Takefumi Hitomi1, Katsuya Kobayashi2, Takayuki Kondo2, Riki Matsumoto2, Ryosuke Takahashi2, Akio Ikeda2 京都大学大学院医学研究科呼吸管理睡眠制御学1, 京都大学神経内科2 Department of Respiratory Care and Sleep Control Medicine, Graduate School of Medicine, Kyoto University, Kyoto, Japan1, Department of Neurology, Kyoto University School of Medicine, Kyoto, Japan2 The clinical anticipation in Japanese benign adult familial myoclonus epilepsy (BAFME), defined as earlier onset age of either cortical tremor or generalized seizures or new appearance of those symptoms in the next generation, remains unknown. To clarify the clinical anticipation in Japanese BAFME, the onset age and the degree of both cortical tremor and generalized seizures were investigated in 9 patients of 4 BAFME families. In addition, we analyzed the relationship between the gender of the transmitting parent and clinical anticipation in 9 BAFME families, since anticipation predominantly occurs in either paternal or maternal transmission.Clinical anticipation in the onset age of cortical tremor or generalized seizures was observed in three families, and generalized seizures newly appeared in the next generation in those two families and in another family. In addition, among 12 parent-child pairs (8 mother-child pairs and 4 father-child pairs) manifesting clinical anticipation in either cortical tremor or generalized seizures, the higher degree of clinical anticipation was observed in maternal transmission than in paternal transmission (P < 0.05).Clinical anticipation was observed in our studied patients, which suggests the clinical progression over generation in Japanese BAFME families. Although the causative gene of BAFME still remains unknown, our finding suggests that BAFME might have similar molecular mechanism to diseases with unstable expanding repeats including those in non-coding regions because such diseases often show clinical anticipation with maternal transmission.	P1-2-209 潜因性点頭てんかん動物モデルにおける成熟後海馬可塑性 Hippocampal synaptic plasticity after development in a rat model of cryptogenic infantile spasms ○辻恵1, 高橋由香里1, 渡部文子1, 加藤総夫1 ○Megumi Tsuji1, Yukari Takahashi1, Ayako M Watabe1, Fusao Kato1 東京慈恵会医科大学大学院　神経生理学研究室1 Lab Neurophysiol, Dept Neurosci, Jikei Univ Sch Med1 Infantile spasms (IS), a specific type of seizure in a catastrophic epilepsy syndrome of infancy and childhood, are strongly associated with cognitive impairment and psychosocial morbidity in adolescence and adulthood even after the achievement of seizure remission. The etiology as well as the mechanism underlying such remote influence of cryptogenic IS to the higher brain function remains unidentified. To address this issue, we made an animal model of cryptogenic IS according to a method recently developed by Velisek et al (2010) and analyzed the long-term potentiation in the hippocampus after development. Pregnant Sprague-Dawley rats were treated with betamethasone (0.4 mg/kg, i.p.) and the offsprings were injected with NMDA (15 mg/kg, i.p.) at postnatal day 15. NMDA injection resulted in hyperactive state followed by repeated flexion spasms observed for 30-60 minutes and irregular high voltage spike bursts between the hyperactive states in the electroencephalogram recorded in a part of the animals. At postnatal week 6-8, hippocampal slices were made from these animals showing IS episodes and also from those treated with ACTH. The IS group without ACTH treatment showed weaker establishment and faster decay of synaptic potentiation during 45 min observation in the CA1 after tetanic stimulation of Schaffer collaterals, suggesting that IS and its treatment during infancy would affect properties of hippocampal synaptic plasticity appearing later in life.
P1-2-210 Cingulate neuronal avalanche regulated by the level of excitation and thalamic input in seizure-like network dynamics ○Jose Jiun-Shian Wu1,3, Wei-Pang Chang1,3, Hsi-Chien Shih1, Bai-Chyang Shyu1 Institute of Biomedical Science, Academia Sinica1, Institute of Zoology, National Taiwan University2 One of the fundamental questions of system neuroscience concerns the functional role of temporal characteristics of neuronal firing. How the neuronal networks regulate the complex neuronal signal transferring and processing in neuronal network is a raising issue in this field. Previous studies propose a neuronal avalanches model to evaluate the neuronal networks. This theoretical investigation was triggered by linking of the occurrence of power laws to the notion of self-organized criticality. This scale-free property suggests a dynamic network for the signal processing. Our previous study approve that this model could evaluate the brain state in nociception processing. In this study, we test this theoretical model in the pathological seizure activity in anterior cingulate cortex with a thalamic modulation. Our results indicated that the epileptic activities propagation obey the neuronal avalanche model in vivo and in vitro. The critical state in the network dynamics represent a excitation/inhibition balance under physiological conditions. The slope of the power-law could be an index of the network properties for the brain state evaluation.	P1-2-211 Identification of a potential target for the treatment of temporal lobe epilepsy ○Lily M.Y. Yu1, Denis Polygalov1, Thomas J. McHugh1 RIKEN Brain Science Institute1 Temporal Lobe Epilepsy (TLE) is a clinical issue worldwide. Understanding the loci involved in epileptogenesis is important for the design of better therapeutic strategies. One region implicated in TLE is the hippocampus. The hippocampal CA3 subregion, due to its direct monosynaptic output projections to CA1 and strong recurrent connections that synapse back to CA3, is anatomically positioned to regulate both intra- and inter-subfield activity. As TLE is linked with neuronal hypersynchrony, we proposed that CA3 may act as a site for the regulation of TLE-associated activity. To test the involvement of CA3 in TLE, we used a mouse line in which CA3 output can be specifically eliminated (CA3 TeTX MT, Nakashiba et al., 2009). An in vivo model of TLE (kainic acid (KA)) was used to assess physiological and behavioral parameters in CA3 TeTX mutant (MT) and wildtype littermates (WT). In vivo recordings from the S. Radiatum of CA1 revealed an increase in low gamma (LG), high gamma (HG) and theta (T) amplitude in WT mice after KA suggesting that increases in oscillatory activity are linked with KA-TLE. However, analysis of CA3 MT showed no significant differences in LG, HG or T amplitude, indicating that CA3 output is required for the generation of KA-TLE associated increases in network oscillations. Behavioral seizures were monitored in MT and WT mice after KA and classified using a modified Racine scale. Analysis revealed that the latency to stage 3 seizures was shorter in WT than MT. MT also had a lower maximal and cumulative seizure score than WT mice. This result indicates that seizure susceptibility is attenuated in CA3 MT mice. Our study has revealed that the CA3 subfield is critical for the generation of epileptiform high amplitude oscillatory events and modulates behavioral seizures during KA-TLE. Thus, CA3 maybe a critical locus for epilepsy and targeted modulation of CA3 excitatory output maybe a novel and effective strategy for the treatment of TLE.

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