学習・長期記憶 Learning and Long-term Memory
P2-2-172 学習行動からみるタンパク質リン酸化酵素Cの活性化による記憶の強化 Memory consolidation by activation of protein kinase C ○榊原学1 ○Manabu Sakakibara1 東海大・開発工・生物工1 Dept Biol Sci Tech, Tokai Univ, Numazu1 In Lymnaea stagnalis, short term memory (STM) of taste avoidance conditioning (TAC) that persists for approximately ten minutes was acquired by at least ten pairs of presentations of associative conditioning stimuli; (CS), sucrose, and the unconditioning stimulus (US), tactile stimulation to the animal's head. Pre-exposure to the protein kinase C (PKC) activator, bryostatin (Bryo), facilitated STM formation with only 5 pairs of CS/US conditioning, but that memory did not manifest itself until 24-hr later. However with 10 pairs of CS/US conditioning coupled with prior bryostatin exposure, snails acquired long term memory (LTM) that persisted for at least 24 h. With 20 paired CS/US presentations, Bryo progressively facilitated the transition from STM to LTM, and LTM to consolidated LTM (CLTM). Conversely, pre-exposure to a specific PKC antagonist, Ro-32 prior to Bryo incubation, or incubation solely with Ro-32 prevented LTN formation, but STM did form. Regardless of the timing of Bryo incubation, STM and LTM were achieved in all the animals (n=57) tested. CLTM lasting longer than 48 h was acquired by Bryo incubation administered 45 min after termination of the conditioning paradigm.	P2-2-173 若齢マウスにおけるPDE3阻害剤Cilostazolの記憶改善効果 Cilostazol, a PDE3 inhibitor, improves learning and memory in mice ○柳井修一1, 仙葉悠紀1, 遠藤昌吾1 ○Shuichi Yanai1, Yuki Semba1, Shogo Endo1 東京都健康長寿医療センター研究所1 Tokyo Metropolitan Institute of Gerontology1 cAMP pathway play essential roles on learning and memory in many species. PDE (phosphodiesterase) inhibitors, used in many pharmacological experiments, exert their physiological functions by increasing cellular cAMP concentration. Several PDE isoform specific inhibitors were developed. One of these compounds, Cilostazol is a specific PDE3 inhibitor and widely used as an antiplatelet agent. Its effects on memory, however, have not been examined in detail though cAMP pathway has been considered to be a target for impaired memories caused by aging and diseases. We examined the effect of Cilostazol on the behavioral tasks in young mice. Mice (C57BL/6J, 10-12 weeks of age) were divided into the behavioral test battery group and the fear conditioning group. In each case, Cilostazol (0-300 mg/k BW) was administered orally 30 min prior to the experiments. In the behavioral test battery group, no apparent effects of Cilostazol were observed on the open field test, the acquisition of the Morris water maze task, or home cage activity. In the probe test of the water maze task, however, number of platform crossings for Cilostazol-administered groups (30, 60, and 300mg/kg) were significantly higher than the control group, suggesting that Cilostazol improved the retention and/or recollection of spatial memory. In the fear conditioning, mice were examined using either context-dependent or cue-dependent fear memory. These tests were conducted 1 hour, 24 hours, and 7 days after the initial conditioning. The conditioned freezing observed for cue-dependent memory test were similar between the Cilostazol-administered and the control mice, however, Cilostazol-administered mice (30 and 100 mg/kg) exhibited significantly higher performance in the context-dependent memory tested on 7 days after conditioning. The results suggest that PDE3 inhibitor, Cilostazol, improves memory, especially in the hippocampus-dependent tasks. Cilostazol may be a novel drug to improve impaired memory functions.
P2-2-174 鳥類刻印付け感受性期の開始を決定するメモリープライミング Memory priming to start the sensitive period of visual imprinting and prime later learning ○山口真二1, 青木直哉1, 北島孝明1, 松島俊也2, 本間光一1 ○Shinji Yamaguchi1, Naoya Aoki1, Takaaki Kitajima1, Toshiya Matsushima2, Koichi Homma1 帝京大・薬学部1, 北海道大院・理・行動知能2 Faculty of pharmaceutical Sciences, Teikyo University, Tokyo1, Department of Biology, Faculty of Science, Hokkaido University, Hokkaido2 Filial imprinting in precocial birds has been studied intensively. Newly hatched chicks and ducklings follow the first conspicuous moving object they see. This is the mother under natural conditions. However, under experimental conditions it can be any other object. While following, the birds learn the color and shape of the object and become attached to it. This learning behavior, called filial imprinting, is restricted to a sensitive period which lasts only a few days in the case of chicks and ducklings. There are several theories concerning the control of the time course of this sensitive period about which very little was known, including the existence of a determining factor. Here we show for the first time that the thyroid hormone 3,5,3'-triiodothyronine (T3) determines the opening of the sensitive period. Imprinting training in chicks causes rapid inflow of T3, converted from circulating plasma thyroxine by Dio2, type 2 iodothyronine deiodinase, in brain vascular endothelial cells. The T3 thus released opens and extends the sensitive period to last over one week via a non-genomic action and primes subsequent learning. Even in non-imprinted chicks whose sensitive period had closed, exogenous T3 enabled imprinting. Our findings indicate that T3 determines the start of the sensitive period of imprinting and plays a critical role in later learning.	P2-2-175 GirdinはNMDA受容体の関与により神経可塑性に重要な役割を果たす Girdin plays a crucial role in neuronal plasticity through NMDA receptors ○中井剛1, 永井拓1, 田中基樹2, 浅井直也3, 榎本篤3, 曽我部正博2, 高橋雅英3, 山田清文1 ○Tsuyoshi Nakai1, Taku Nagai1, Motoki Tanaka2, Naoya Asai3, Atsushi Enomoto3, Masahiro Sokabe2, Masahide Takahashi3, Kiyofumi Yamada1 名古屋大院・医・医療薬1, 名古屋大院・医・細胞物理2, 名古屋大院・医・腫瘍病理3 Dept. Neuropsychophamacol. & Hosp. Pharm., Nagoya Univ. Grad. Sch. Med.1, Dept. Physiol., Nagoya Univ. Grad. Sch. Med.2, Dept. Pathol., Nagoya Univ. Grad. Sch. Med.3 Girders of actin filament (Girdin), an actin-binding protein involved in both the remodeling of the actin cytoskeleton and in cell motility, has been identified as a substrate of the serine/threonine kinase Akt. Girdin interacts with Disrupted-In-Schizophrenia-1 (DISC1), a susceptibility gene for major psychiatric disorders, to regulate axonal development and neurogenesis in the dentate gyrus (DG) of hippocampus. Furthermore, it was reported that Akt-mediated phosphorylation of Girdin at serine-1416 has an important role in the motility of breast cancer and endothelial cells. However, the role of phosphorylated Girdin in the central nervous system remains largely unknown. In the present study, we demonstrated that Girdin knockin (Girdin SA) mice, in which serine-1416 of Girdin is replaced by alanine, have learning and memory impairments in novel object recognition, fear conditioning (FC) and Morris water maze tests. The long-term potentiation (LTP) induced by high-frequency stimulation at the medial perforant path-granule cell synapses was impaired in the hippocampal slices of Girdin SA mice compared to wild-type (WT) mice. The AMPA/NMDA ratio recorded from the DG of hippocampus in Girdin SA mice was significantly increased compared to that in WT mice. The application of BDNF (50 ng/mL) significantly increased the level of phosphorylated NMDA receptor 2B subunit (NR2B) at tyrosine-1472 in the hippocampal neurons of WT mice compared to control group, whereas the same treatment failed to increase the phosphorylated level in Girdin SA mice. There was no difference in NR2B expression level of hippocampal neurons between WT and Girdin SA mice. The levels of phosphorylated NR2B at tyrosine-1472 and Girdin at serine-1416 in the DG of hippocampus were significantly increased after training trials in the FC test. These findings suggest that phosphorylation of Girdin in the hippocampus plays a crucial role in learning and memory formation.
P2-2-176 線虫の学習行動に対するニコチンの影響 Inhibition of salt chemotaxis learning due to acute nicotine exposure in Caenorhabbditis elegans ○松浦哲也1, 三浦仁志1 ○Tetsuya Matsuura1, Hitoshi Miura1 岩手大・工・応化生命1 Dept Chem Bioeng, Iwate Univ, Morioka, Japan1 Nicotine exposure is a major health concern for humans and exerts deleterious effects on motor activity and thus learning in many animals. In the present study, we found that nicotine is an attractant that impairs salt chemotaxis learning in the nematode Caenorhabbditis elegans. Among various nicotine concentrations (0.1-5.0 mM), wild-type N2 nematodes exhibited maximal attractive response to 1.0 mM nicotine. Decrease in spontaneous locomotion was observed in the N2 nematodes, which were exposed to 3.0 and 5.0 mM nicotine, compared with the non-exposed nematodes. For 100 mM NaCl, the chemotaxis index of N2 nematodes pre-exposed to NaCl with 1.0 and 3.0 mM nicotine was greater than that of nematodes pre-exposed to NaCl without nicotine (p<0.05). No significant difference was observed in spontaneous locomotion and chemotactic response to NaCl between nicotine pre-exposed and non-exposed nematodes. The results indicate that salt chemotaxis learning is inhibited by acute nicotine exposure. To clarify the mechanism of inhibition, several mutants were analyzed. When cat-2 mutants with a defect in dopamine secretion were pre-exposed to NaCl with 3.0 mM nicotine, the chemotaxis index for NaCl was greater than that of mutants pre-exposed to NaCl without nicotine (p<0.05). However, when bas-1 and tph-1 mutants, which had a defect in serotonin and dopamine secretion and serotonin secretion alone, respectively, were pre-exposed to NaCl with 3.0 mM nicotine, the chemotaxis index for NaCl was almost the same as that of mutants pre-exposed to NaCl without nicotine. These all mutants demonstrated salt chemotaxis learning in the absence of nicotine during conditioning period. The observations indicate that salt chemotaxis learning was inhibited by nicotine in cat-2 mutants but not in bas-1 and tph-1 mutants and suggest that serotonin signaling has an essential role in modulating the acute effects of nicotine.	P2-2-177 ラット内側嗅内野単一ニューロンの軸索分岐様式 Patterns of axonal collateralization of single neurons in the rat medial entorhinal area ○本多祥子1, 古田貴寛2, 金子武嗣2 ○Yoshiko Honda1, Takahiro Furuta2, Takeshi Kaneko2 東京女子医大・医・解剖1, 京都大院・医・高次脳形態2 Dept Anatomy, Sch Med, Tokyo Women's Medical Univ, Tokyo1, Dept Morphological Brain Sci, Grad Sch Med, Kyoto Univ, Kyoto2 We studied the axonal morphology of single neurons of the medial entorhinal area (MEA), which were visualized in the rat with a viral vector expressing membrane-targeted green fluorescent protein. A single pyramidal neuron in layer III of MEA had four major axon collaterals, one of which reached molecular layer of the subiculum and the others recurrently reached layers I-V of MEA. A single pyramidal neuron in layer V of MEA had two axon collaterals that projected to layer VI of the more lateral part of MEA, one axon collateral that reached layers III-V of the presubiculum (PreS), and one entered the white matter. A single non-pyramidal layer VI neuron in MEA had three axon collaterals; one innervated layer VI of PreS and two recurrently reached layer VI of MEA.
P2-2-178 サル下側頭葉皮質と前頭前野からの皮質脳波を用いて、想起された視覚記憶をデコーディングする Decoding recalled visual memory using electrocorticographic (ECoG) signals in macaque inferior temporal and prefrontal cortices ○谷川久1, 間島慶2,3, 川嵜圭祐1, 澤畑博人1, 中原潔4, 鈴木隆文5, 神谷之康2,3, 長谷川功1,4 ○Hisashi Tanigawa1, Kei Majima2,3, Keisuke Kawasaki1, Hirohito Sawahata1, Kiyoshi Nakahara4, Takafumi Suzuki5, Yukiyasu Kamitani2,3, Isao Hasegawa1,4 新潟大学大学院 医歯学総合研究科 神経生理学分野1, ATR脳情報研究所 神経情報学研究室2, 奈良先端科学技術大学院大学3, 新潟大学 超域学術院4, 情報通信研究機構 脳情報通信融合研究センター5 Dept Physiol, Niigata Univ Grad Sch of Med & Dent Sci, Niigata, Japan1, Dept Neuroinformat, ATR Comput Neurosci Lab, Kyoto, Japan2, Grad Sch of Info Sci, NAIST, Nara, Japan3, Cent for Transdiscipl Res, Niigata Univ, Niigata, Japan4, Cent for Info & Neural Net, Natl Inst of Info & Comm Tech, Osaka, Japan5 Reading out mental content from brain activity is one of challenging goals in neuroscience. For this purpose, multichannel subdural electrocorticography (ECoG) is a promising tool because of its ability to record surface field potential with broad spatial coverage, high temporal resolution, and high signal fidelity. In this study, we are attempting to decode recalled visual memory using ECoG signals in macaques. We implanted 128- and 64-channel ECoG electrode arrays with 2.5-mm spaced grid configuration on the inferior temporal and prefrontal cortices, respectively, which are known to be important for memory recall. Monkeys performed a memory recall task. An achromatic scene image was presented as a cue stimulus, and after a delay period, 1-2 object images or colored shapes were sequentially presented as choice stimuli. The monkeys released a lever upon the presentation of correct choice that was associated with the cue, to receive a reward. The monkeys were supposed to recall and maintain visual memory during the delay period. As a control, they also performed a passive viewing task, in which they received a reward after the delay period without choice presentation. For decoding analysis, we used ECoG signals recorded during the delay period. We calculated power spectrum of signals in each channel and each trial. Using the powers of frequency bands, time windows and channels as input features, we trained a support vector machine classifier (decoder) to predict monkey's choice selection. At this point, we have collected data from one monkey. The prediction success rate by the decoders was significantly higher than chance level in the memory recall task, but not in the passive viewing task. This proved that ECoG potentially provides an ability to read out memory content.	P2-2-179 長期記憶想起におけるサル内側側頭皮質脳波の周波数間結合 Cross-frequency coupling of cortical oscillations during long-term memory retrieval in the monkey medial temporal lobe ○安達賢1, 川嵜圭佑2, 澤畑博人2, 松尾健3, 鈴木隆文4, 谷川久2, 飯島淳彦1, 長谷川功2,5, 中原潔5 ○Ken Adachi1, Keisuke Kawasaki2, Hirohito Sawahata2, Takeshi Matsuo3, Takafumi Suzuki4, Hisashi Tanigawa2, Atsuhiko Iijima1, Isao Hasegawa2,5, Kiyoshi Nakahara5 新潟大院・自然科学研究科1, 新潟大院・医・神経生理学2, 東京大院・医・脳外3, 情報通信研究機構・脳情報通信融合研究セ4, 新潟大・超域学術院5 Grad Sch of Sci and Tech, Niigata Univ, Niigata, Japan1, Dept of Physiol, Niigata Univ Grad Sch of Med and Dent Sci, Niigata, Japan2, Dept of Neurosurgery, The Univ of Tokyo Sch of Med, Tokyo, Japan3, CiNet NICT, Osaka, Japan4, Cent for Transdisciplinary Res, Niigata Univ, Niigata, Japan5 To explore the spatio-temporal dynamics of cortical activities associated with long-term memory retrieval, we conducted multi-channel electrocorticogram (ECoG) recordings from the inferior and medial temporal cortices, in two macaque monkeys while they performed a visual pair-association task. The monkeys were trained to memorize five pairs of visual stimulus-stimulus associations, and subdurally implanted with a 128-channel ECoG electrode grid spanning from anterior TE to the perirhinal cortex. Multi-channel ECoG was recorded while monkeys performed the memory task. In each task trial, one of the visual items was presented as a cue (1 sec), then one to three choice stimuli were sequentially presented after a delay (1.5 sec). The choice stimulus was either the paired-associate of the cue or a distractor selected from a different pair. The monkeys were required to maintain central fixation and release a lever immediately when the correct paired-associate was presented. We detected ECoG responses evoked at the onset of cue presentation with the majority of electrode channels. These cue-related responses were significantly selective to the visual items at several localized channel locations. During the delay period, oscillatory ECoG gamma activity was detected at localized channels. Time-frequency analyses revealed that the amplitude of gamma activity was prominently modulated in relation to a particular phase of local theta wave activity, so-called cross-frequency coupling. Gamma activity was not observed during the cue period, but emerged and gradually increased from the middle toward the end of the delay period. Our results suggest that the gamma oscillation and its cross-frequency coupling to the theta wave in the medial temporal lobe are involved in mechanisms of memory retrieval.
P2-2-180 視床外側中心核と束傍核から背外側線条体へ入力する神経路の行動学的役割に関する比較解析 Comparative analysis for behavioral roles of the central lateral and parafascicular nuclear groups projecting to the dorsolateral striatum ○加藤成樹1, 深堀良二1, 小林和人1,2 ○Shigeki Kato1, Ryoji Fukabori1, Kazuto Kobayashi1,2 福島医大・医・生体機能1 Dept. Mol. Genet., Fukushima Med. Univ.1, CREST/JST, Kawaguchi, Japan2 The dorsal striatum is a key structure of the basal ganglia circuitry and mediates learning processes contributing to instrumental motor actions. Anatomically, the dorsolateral striatum (DLS) receives glutamatergic excitatory afferents from sensorimotor cortical areas and the intralaminar thalamic nuclei, including the central lateral nucleus (CL) and parafascicular nucleus (PF), in addition to dopaminergic projections from the substantia nigra pars compacta. In rodents, the CL and PF are localized in the rostral and caudal regions of the intralaminar thalamic nuclei and both thalamic nuclei project directly to medium spiny neurons. We addressed the roles of the thalamostriatal pathways arising from the CL or PF in learning processes by using immunotoxin (IT)-mediated cell targeting. A receptor molecule for the recombinant IT (Human IL-2Rα) was expressed in the neurons by using a highly efficient retrograde gene transfer (HiRet) vector. Injection of the HiRet vector into the DLS of mice yielded efficient gene transfer via retrograde axonal transport into the cerebral cortex, thalamus, and ventral midbrain, which innervate the striatum. Treatment with IT into the CL or PF in the HiRet vector-injected mice induced a selective, efficient elimination of the rostral or caudal thalamostriatal pathway. The elimination of the caudal thalamostriatal pathway impaired the acquisition of a visual discrimination task, which was accompanied by an increase in the correct response time and omission ratio. In addition, this pathway elimination after the acquisition of the discrimination task resulted in the impaired accuracy of motor selection. The behaviors of mice lacking the rostral thalamostraital pathway will be presented to compare the behavioral roles of the two thalamostraital pathways.	P2-2-181 ショウジョウバエapterous遺伝子依存的な長期記憶にかかわる脳神経細胞の同定 Mapping brain neurons involoved in apterous-dependent regulation of long-term courtship memory in Drosophila ○井並頌1, 朝野綱起1, 坂井貴臣1 ○Shou Inami1, Tsunaki Asano1, Takaomi Sakai1 首都大院・理・生命科学1 Dept Biological Sciences, Tokyo metropolitan Univ. Tokyo1 In Drosophila, there are at least two memory phases. They are short-lasting memory, which lasts minutes or hours, and long-term memory (LTM), which is maintained for several days. LTM formation depends on newly protein synthesis during and/or after training, suggesting that transcriptional factors play a crucial role in LTM formation. Previously, we demonstrated that apterous (ap) mutants are defective for LTM, using a courtship-conditioning assay, where previous experiences with mated females causes males to subsequently reduce their courtship toward virgin females (The 32th and 35th Annual Meeting of the Japan Neuroscience Society). The ap gene encodes the LIM homeodomain (LIM-HD) transcriptional factor, which is conserved from vertebrate to invertebrate. In this current study, we used Anti-Ap antibody to identify Ap-expressing neurons in the adult brain. Ap-immunoreactivity was detected in some MB Kenyon cells (KCs) and two pairs of neuropeptide F (NPF) expressing neurons. Next, we used flies with a GFP fusion knock-in allele of ap (ap::GFP) and observed GFP-expressing neurons in the adult brain. GFP should be expressed in a pattern consistent with expression of the endogenous ap mRNA in this knock-in allele. In ap::GFP flies, GFP expression was detected in some KCs and pigment-dispersing factor (PDF) neuropeptide-expressing neurons, famous for circadian pacemaker neuron. Furthermore, targeted expression of ap RNAi in the MBs, NPF, and PDF-neurons resulted in defective courtship LTM, indicating that the MBs, NPF, and PDF-neurons are involved in ap-dependent courtship LTM. Although further studies are required for a better understanding the molecular and cellular mechanisms of the functional interactions between the MBs and NPF/PDF-neurons, our results indicate that not only the MB-neurons but also the neuropeptide-expressing neurons play a role in formation of courtship LTM.
P2-2-182 Effect of X-irradiation on learning, cell death and synaptic proteins Effect of X-irradiation on learning, cell death and synaptic proteins 小金澤紀子1, 児島伸彦1, 白尾智明1 ○Puspitasari Anggraeini1, Noriko Koganezawa1, Nobuhiko Kojima1, Tomoaki Shirao1 群馬大院・医・神経薬理学1 Department of Neurobiology and Behavior, Gunma University Graduate School of Medicine, Maebashi, Japan1 Cranial X-irradiation causes serious damages on higher brain function. However the underlying mechanism is still uncertain. We conducted fear conditioning in mice to evaluate effects of X-irradiation on the cognitive function. 10 Gy of irradiation (less than 30 min) after conditioning disrupted the formation of fear memory, whereas the irradiation at 24 hr prior to conditioning had no effect. We next investigated the effects of X-irradiation on cell death and the accumulation level of synaptic proteins in vivo. Left hemispheres of 10-week-old male C57BL/6 mouse brains were irradiated with a single dose of 10 Gy, and the localization of drebrin and Synapsin I was compared between the irradiated and non-irradiated sides. Mice were sacrificed within 30 min, and at 2 hr, 24 hr and 48 hr after the irradiation. The immunofluorescence images of the molecular layer (ML) of the dentate gyrus, the striatum, and the subventricular zone (SVZ) of the lateral ventricle were analyzed. Apoptosis was identified by TUNEL staining. The intensities of drebrin and synapsin I were decreased in the irradiated side of ML and the striatum at 2 hr. Unexpectedly, the staining intensities of those proteins tended to be increased at 24 hr compared to 2 hr indicating that the effect of X-irradiation on synapses were transient. The number of doublecortin-positive neurons was decreased in 24 hr, and TUNEL-positive cells appeared at 2 hr after the irradiation. Since the irradiation at 24 hr prior to conditioning had no effect on fear memory, the irradiation-induced cell death of newly-generated neurons seems not to be related to the fear memory formation. Because X-irradiation caused the transient change of synaptic protein accumulation and the inability of fear memory formation in a similar time dependent manner, it is indicated that the transient change of synaptic function might cause memory deficit in the X-irradiated animals.	P2-2-183 Cdk5/p35は空間学習・記憶に必須である Cdk5/p35 is required for spatial learning and memory ○三柴智英1, 三田直輝1, 笹本宏大1, 糸原重美2, 大島登志男1 ○Tomohide Mishiba1, Naoki Mita1, Kodai Sasamoto1, Shigeyoshi Itohara2, Toshio Ohshima1 早稲田大院・先進理工・生命医科1, 理化学研究所 脳科学総合研究センター2 Dept. of Life Sci. Med. Bio Sci., Sch. of Adv. Sci. Eng., Waseda Univ., Tokyo1, Lab. for Behav. Genet., BSI, RIKEN2 Cdk5, which is a kinase abundant in neuronal cells and activated by making complexes with p35 or p39, is involved in brain development, synaptic plasticity, and neurological disorders. Especially, Cdk5/p35 has a significant influence on various signaling pathways in the nervous system. In Cdk5 KO/cKO and p35 KO mice, the laminar structures of the cerebral cortex and cerebellum are disrupted. Therefore, inducible p35 cKO mice were generated in order to exclude that secondary consequence in brain development and clarify the role of Cdk5/p35 in higher brain function. After the deletion of p35 in an adult stage, inducible p35 cKO mice showed less anxiety-like behavior, the impairment of spatial learning and memory, and the defective contextual memory. These results suggest that Cdk5/p35 is essential in higher brain function and that Cdk5/p35 is a therapeutic target of neurological disorders by modification of its activity.
P2-2-184 物体認識記憶における海馬歯状回の顆粒細胞内亜鉛シグナルの関与 Involvement of Zn2+ signal in dentate granule cells in object recognition memory ○玉野春南1, 小川泰右1, 高田俊介1, 奥直人1, 武田厚司1 ○Haruna Tamano1, Taisuke Ogawa1, Shunsuke Takada1, Naoto Oku1, Atsushi Takeda1 静岡県大院・薬・生物薬品化学1 Dept Biooranic Chem, Grad Sch of Pharm, Univ of Shizuoka, Shizuoka, Japan1 Zinc is released from glutamatergic neuron terminals in the hippocampus and may serve as a signal factor. We have demonstrated that dentate gyrus long term-potentiation (LTP) and object recognition memory are transiently impaired after intraperitoneal injection of clioquinol, a membrane-permeable zinc chelator into young rats, which transiently decreases synaptic Zn2+ levels in the hippocampus, especially in the dentate gyrus. To pursue the role of Zn2+ signal in dentate granule cells in object recognition memory, in the present study, ZnAF-2DA (100 pmol, 0.1 mM/1 μl), a membrane-permeable zinc chelator, was injected into the dentate molecular layer. The training of the object recognition task was performed 1 h after the injection. One hour after the training, object recognition memory was impaired in ZnAF-2DA-injected rats. The confocal laser-scanning microscopic study imaging intracellular Zn2+ with ZnAF-2DA showed that zinc chelation with ZnAF-2DA injected is restricted only in the dentate gyrus 1 h after the injection. Moreover, ZnAF-2DA in the dentate gyrus chelated intracellular Zn2+ increased by high K+ stimulation, suggesting that ZnAF-2DA in the dentate gyrus chelates intracellular Zn2+ increased during the training. In anesthetized rats, on the other hand, dentate gyrus LTP, which was induced by tetanic stimulation (200 Hz, 0.1 s, 10 times) of perforant pathway under perfusion of dentate molecular layer with zinc chelators via a microdialysis probe attached to a recording electrode, was attenuated under perfusion with ZnAF-2DA (0.1 mM), but not under perfusion with CaEDTA (1-10 mM), a membrane-impermeable zinc chelator. These results suggest that intracellular Zn2+ signal in dentate granule cells is required for dentate gyrus LTP induction. Taken together, the present study demonstrates that intracellular Zn2+ signal in dentate granule cells may be required for object recognition memory.	P2-2-185 海馬は文脈情報を階層化してエピソードを形成する Hippocampus hierarchically organizes contexts as a single episode ○高橋晋1 ○Susumu Takahashi1 同志社大学大学院　脳科学研究科1 Graduate School of Brain Science, Doshisha University1 Hippocampal place cells specifically fire at a certain location (the 'place field'). The place field of a given neuron remaps relative to three different contexts: spatial context, spatiotemporal context (journey), and non-spatial context (task-demand), suggesting that the hippocampal place code is not only closely related to the 'where' of episodic memory but also to the 'when and how'. To check the dynamics of the hippocampal place code in terms of episodic-like memory, I conducted a multifaceted experiment in which many hippocampal neurons are simultaneously monitored during repeated exposures to either spatiotemporal or non-spatial contexts in a constant spatial environment. Rats were trained to navigate their way through a figure-eight maze in a continuous task that incorporated both visual discrimination, and non-delayed and delayed spatial alternations. Ensemble activity was recorded from a total of 1,119 pyramidal cells in the CA1 of the dorsal hippocampus using arrays of ten extracellular dodecatrodes in five rats running in the maze. The results suggested that the spatial representation of the hippocampal CA1 was dissimilar in both firing location and rate among different journeys, irrespective of either visually or mnemonically guided demands, in a global remapping manner. In contrast, when the rats experienced changes in non-spatial features with internal and external events, the hippocampus only modulated the journey-dependent activity by primarily changing the intensity of the firing rates in a rate remapping manner. At the ensemble level, even when the given task-demands were different, the classifier could sufficiently predict the journey from the ensemble activity patterns, suggesting that the journey representation is generalized and that non-spatial demand-specific representation is hierarchically ranked at a lower level. Therefore, the results imply that the hippocampus processes the combination of journey and task-demand as a single episode.

上部に戻る

前に戻る