学習・長期記憶 Learning and Long-term Memory
P1-1-182 聴覚弁別学習の遂行における背内側線条体から投射する線条体投射路の機能解析 Behavioral roles of the striatal output pathway from the dorsomedial striatum in the auditory discrimination task ○西澤佳代1, 深堀良二1, 岡田佳奈2, 内ヶ島基政3, 渡辺雅彦3, 塩田明4, 上田正次4, 筒井雄二5, 小林和人1 ○Kayo Nishizawa1, Ryoji Fukabori1, Kana Okada2, Motokazu Uchigashima3, Masahiko Watanabe3, Akira Shiota4, Masatsugu Ueda4, Yuji Tsutsui5, Kazuto Kobayashi1 福島県立医大・医・生体機能1, 広大・総合・行動科学2, 北大・医・解剖発生3, フェニックスバイオ4, 福大・共生理工・人間支援5 Dept Mol Genet, Fukushima Medical University School of Medicine, Fukushima, Japan1, Dept of Behavioral Science, Hiroshima, Japan2, Dept of Anatomy and Embryology, Hokkaido University Graduate School of Medicine, Hokkaido, Japan3, PhoenixBio Co., Ltd. Japan4, Dept Human Support System, Fukushima University, Fukushima, Japan5 The dorsal striatum, which contains the the dorsomedial striatum (DMS) and dorsolateral striatum (DLS), integrates the acquisition and performance of instrumental learning. For instance, excitotoxic lesion of striatal neurons disturbs choice accuracy of learned motor response and reduces their responding rate in conditional discrimination. The dorsal striatum receives excitatory inputs from many cortical areas and the thalamic nuclei and projects to the output nuclei through two major pathways composed of the direct and indirect pathways. The balance between opposing inputs from these two pathways is considered to be implicated in motor control though the regulation of basal ganglia output activity. We found that the DLS-derived striatopallidal pathway plays an essential role in the execution of conditional discrimination, showing its contribution to the control of selection accuracy of learned motor responses (Nishizawa et al., 2012). However the mechanism by which the striatopallidal pathway arising from DMS mediate the learning processes of instrumental actions remains unclear. To determine the behavioral processes through the DMS striatopallidal pathway, we induced selective elimination of the striatopallidal pathway by injecting the recombinant immunotoxin into the DMS of transgenic rats that expressed human interleukin-2 receptor &alpha-subunit under the control of dopamine D2 receptor gene promoter. Then we examined the behavioral consequence of striatopallidal elimination on the performance of auditory discrimination task. We report the roles of the DMS striatopallidal pathway in the control of response selection accuracy and response time in the discriminative behavior.	P1-1-183 モノアシルグリセロールリパーゼ欠損マウスにおける海馬依存性記憶機能の包括的評価 Comprehensive assessment of hippocampus-dependent memory function for mice deficient in monoacylglycerol lipase ○岸本泰司1, , 山崎真弥3, 中山順子1, 崎村建司3, 桐野豊1, 狩野方伸2 ○Yasushi Kishimoto1, Barbara Cagniard2, Maya Yamasaki3, Junko Nakayama1, Kenji Sakimura3, Yutaka Kirino1, Masanobu Kano2 徳島文理大・香川薬・生物物理学1, 東京大院・医・神経生理2, 新潟大・脳研・細胞神経生物3 Lab of Neurobiopysics, Tokushima Bunri Univ, Sanuki, Japan1, Dept Neurophysiol, Univ of Tokyo, Tokyo2, Dept Cell Neurobiol, Brain Res Inst, Niigata Univ, Niigata3 Growing evidence indicates that the endocannabinoid system is important for the acquisition and/or extinction of certain forms of memory. However, it is unclear which of the two major endocannabinoids, anandamide and 2-arachidonoylglycerol (2-AG), is involved in memory acquisition/extinction. To elucidate physiological roles of 2-AG in hippocampal memory functions, we conducted five hippocampus-dependent behavioral paradigms (i.e., Morris water maze [MWM], contextual fear conditioning, novel object recognition test, trace eyeblink conditioning, and water-finding test) in mice deficient in the 2-AG hydrolyzing enzyme monoacylglycerol lipase (MGL KO mice). On the MWM task, acquisition of reference memory was normal in MGL KO mice. However, after acquisition, MGL KO mice exhibited a significantly faster extinction of the learned behavior. In contrast, MGL KO mice tended to exhibit slower extinction of conditioned fear in the contextual fear conditioning paradigm. In the novel object recognition test and water-finding test, MGL KO mice exhibited enhanced memory acquisition. Finally, trace eyeblink conditioning was unaltered in MGL KO mice throughout the acquisition and extinction phases. These results suggest that 2-AG-mediated endocannabinoid signaling plays variable roles in learning and memory depending on tasks, although all the tasks used are known to be hippocampus-dependent. Our data support the hypothesis that 2-AG signaling plays a crucial role in the extinction of spatial and aversive memories.
P1-1-184 恐怖条件付け学習時に活動した神経細胞群の人為的再活性化 Artificial reactivation of a specific ensemble of neurons activated during fear-conditioned learning ○吉井隆浩1, 細川浩1松尾直毅3 ○Takahiro Yoshii1, Hiroshi Hosokawa1, Bryan Roth2, Naoki Matsuo3 京都大院・情報・知能情報1, 京都大・白眉センター3 Dept Intelligence Sci., Kyoto Univ, Kyoto1, Univ. of North Carolina Chapel Hill Med. School, USA2, The HAKUBI Center, Kyoto Univ, Kyoto3 Memory is thought to be stored as an engram in the brain. A prevailing hypothesis suggests that a specific ensemble of neurons sparsely distributed in the brain is the unit that stands for a specific information and corresponds to a specific memory engram. To examine the causality between a specific memory and a specific subset of neurons, we investigated whether the selective reactivation of a specific neuronal population that was activated during an acquisition of a fear memory elicits a behavioral output of the fear memory. To remote control the active states of a dispersed neuronal ensemble, we used a combination of transgenic system in mice that allows us a genetic manipulation in those neurons activated by a given behavioral stimulus during a limited time window and the DREADD (Designer Receptor Exclusively Activated by Designer Drug). The transgenic mice express hM3Dq DREADD receptor under the control of tet-off system and the promoter of the c-fos gene, one of the immediate-early genes whose expression is rapidly and transiently induced in response to neuronal activities. hM3Dq is a Gq protein-coupled designer receptor which is exclusively activated by an exogenous designer drug (clozapine-N-oxide, CNO) to induce a neuronal firing.We subjected the transgenic mice to contextual fear conditioning while Dox off so that hM3Dq is expressed specifically in a subset of neurons that was active during fear-conditioned learning. Then, we injected CNO to reactivate selectively the ensemble of neurons, and examined whether the fear memory is retrieved in a distinct context. The results would be an essential clue to understand the memory engram at the cellular and network levels.	P1-1-185 認知課題中における海馬内高周波帯域脳波のセッション内ダイナミクス Within-session dynamics of hippocampal high frequency oscillation during spatial alternation ○西田洋司1, 高橋宗良1,2 ○Hiroshi Nishida1, Muneyoshi Takahashi1,2, A D Redish3, Johan Lauwereyns1,2 九大院・システム生命科学府1, 玉川大・脳科学研2 Grad Sch Sys Life Sci, Kyushu Univ, Fukuoka, Japan1, Brain Sci Inst, Tamagawa Univ, Tokyo, Japan2, Dept Neurosci, Univ of Minnesota, Minnesota, USA3 The hippocampus plays a critical role in encoding and consolidating recent information in episodic memory. Many studies have observed that place cells in the hippocampus are replayed during sharp wave ripple (SWR) events in the waking state. It has been suggested that these activities reflect neural mechanisms toward the updating of memory. However, it remains unclear how the current information is reconstructed on the basis of memory, and how behavioral performance becomes stabilized in a short period.To investigate the underlying mechanisms, we trained rats to perform a spatial alternation task that included a 1-s fixation period, and recorded neural activity for 18 days from four animals. We analyzed the spike timing and the local field potentials from a total of 31 electrodes located in the hippocampal CA1.We found that the reaction time to the choice hole reduced significantly in the later phase of a session as compared to the early phase; thus rats seemed to perform the task more efficiently after adjusting during the session. We also observed SWR events and low gamma activity associated with SWR during eating (at the end of a successful trial). Compared to late in the session, SWR events occurred more often and the power of low gamma was higher early in the session. Furthermore, fixation cells, which fired predominately during the 1-s fixation period, were reactivated during SWR events. The frequency of the reactivation of these cells changed depending on the spatial sequence and the phase of the session. Our findings support the notion that SWRs serve to facilitate and stabilize the task behavior.
P1-1-186 低周波磁場曝露のマウスの空間認知学習に及ぼす影響 Enhanced spatial cognitive learning by the exposure to low frequency magnetic field in mice ○吉原崇博1, 松林宏樹1, 今村一之1 ○Takahiro Yoshihara1, Hiroki Matsubayashi1, Kazuyuki Imamura1 前橋工科大院・工・システム生体1 Dept Systems Life Engineering, Maebashi Institute of Technology, Maebashi, Gunma, Japan1 We examined effects of exposure to low-frequency magnetic field (LFMF, 50 Hz, 10 mT intensity) on spatial cognitive learning (T-maze task) in mice. Male mice (C57BL6N) were exposed daily to LFMF for 30 min in a Helmholtz coil system. During the exposure, mice were kept in a specially designed restrainer by which LFMF was focused to the head region without any anesthesia or sedation. Following the LFMF exposure, T-maze tests (two sessions, one session consists of ten trials) were performed for five successive days. Mice can eat foods as a reward for the correct choices when they chose the lighted arm, while an electric shock (1 mA) was given for incorrect choices when they chose the arm of lamp off. Mice learned to choice the lighted arm. The number of correct choices in T-maze test was measured. We found that the exposed group learned significantly earlier than control group. Cumulative sum analysis showed exposed mice started to learn after the second session, while control mice did after the fourth session or later. The significant difference was detected in second session (30% increase, p<0.01). In addition, we tested the retention of spatial memory. We found that about one week break of the training reduced the number of correct choices. The effects of LFMF exposure during this resting period were examined. T-maze tests were performed at one and two weeks after the last session. During this period, a half of animals were exposed to LFMF without T-maze task. Another half was used as a control without LFMF. Exposed group showed more correct choices than control group (25%, p<0.05). These results indicate that the exposure to LFMF enhances spatial cognitive learning in mice. It is also demonstrated that it delays the diminishing of acquired memory. Therefore, the exposure to LFMF may be applicable to enhance the acquisition and retention of memory.

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