空間・時間認知 Spatial and Temporal Cognition
P3-1-178 視覚性及び聴覚性刺激を用いた時間弁別課題におけるサル前頭前野ニューロンの遅延期応答 Delay period responses of monkey prefrontal neurons during a duration discrimination task with visual and auditory cues ○千葉惇1, 生塩研一1, 稲瀬正彦1 ○Atsushi Chiba1, Ken-ichi Oshio1, Masahiko Inase1 近畿大学医学部生理学1 Dept Physiol, Kinki Univ, Osaka-Sayama, Japan1 To address the role of the prefrontal cortex (PFC) in time perception of different modes of sensory stimuli, we examined neuronal activity in the PFC of two monkeys during a duration discrimination task with visual (Vis, a green square) and auditory (Aud, 2000Hz tone) cues. In the task, two cues (the first cue, C1 and the second cue, C2) were presented consecutively for different duration ranging from 0.2 to 1.8 sec followed by 1 sec delay periods. The subjects were required to choose the longer presented cue. There were four kinds of cue modality combinations; Vis-Vis, Vis-Aud, Aud-Vis and Aud-Aud. Duration of two cues, order of cue duration (long-short, LS or short-long, SL), and cue modality combination were pseudorandomly determined. Correct response rates tended to be better in the SL trials than in the LS trials. The subjects also showed different performance among four cue modality combinations and correct rates for the Aud-Aud trials were lower than those for the other three types. Out of 860 PFC neurons, 35 and 123 neurons responded during the first and second delay (D1 and D2) periods, respectively. Among 35 D1 response neurons, 7 neurons responded after the visual cue, one neuron did following the auditory one, and 27 neurons responded to both modes of stimuli. While 57 neurons, of 192 D2 response neurons, exhibited greater D2 activity in the LS trials than the SL trials, 85 neurons showed greater activity in the SL trials than the LS trials. More than half of these D2 response neurons responded similarly after the visual and auditory C2 and did so among the four cue modality combinations. Specific response following the visual or auditory C2 was rarely found. The D2 response neurons represent order-based timing, whether C1 or C2 was presented longer, irrespective of cue modality. These results suggest that the PFC integrates interval information on different modes of sensory stimuli and contributes to temporal discrimination processing of these stimuli.	P3-1-179 心的回転・視点取得機能に関わる神経基盤の比較:fMRI研究 Shared and different neural bases involved in perspective-taking and metal rotation: An fMRI study ○笹岡貴史1, 乾敏郎1 ○Takafumi Sasaoka1, Toshio Inui1 京都大院・情報学1 Graduate School of Informatics, Kyoto University, Kyoto, Japan1 We can create mental images of a view of an object from a different viewpoint, either by imagining our own locomotion to the different viewpoint or by imagining rotation of the object. The former is called perspective-taking (PT); the latter is called mental rotation (MR). These functions are equivalent in terms of the goal, but whether they share neural substrates is not known at present. In the current study, we employed an MR/PT task in which participants mentally rotated a novel paper clip object on a table or imagined a view of the object as the participant moved around the table in a virtual environment. We measured brain activity with functional MRI while participants performed each task. During both tasks, we observed common and bilateral activations in the ventral premotor and posterior parietal areas. These areas are consistent with those reported in previous mental rotation studies, suggesting that MR and PT share a common network for mental imagery transformation. In addition to this network, the dorsal premotor and supplementary motor areas (SMA) were activated in the MR task. These areas are known to be activated during motor imagery. These activations suggested that motor imagery was utilized for mental rotation. In the PT task, the insula, hippocampus, fusiform gyrus, and precuneus were activated with the premotor-parietal network. Activation of the insula is known to occur by vestibular stimulation and is involved in the sense of agency. Involvement of the precuneus is suggested in the transformation of egocentric information into the allocentric coordinate system. Thus, these activations can be interpreted as the use of imagery of body locomotion. The activations in the hippocampus and fusiform gyrus may reflect the use of object-location memory to solve the PT task. Future study will incorporate the use of stimuli without background information to determine whether these areas are really involved in PT.
P3-1-180 場所細胞活動におけるNMDA受容体の機能：局所RNAi法とマルチユニット記録法の統合 Local RNAi knockdown with unit recording reveals NMDA receptor functions in place cell activity ○北西卓磨1, , 北西なおみ1, 田代歩1,2,3 ○Takuma Kitanishi1, Mehdi Fallahnezhad1,2,3, Naomi Kitanishi1, Ayumu Tashiro1,2,3 CBM, Norwegian Univ Science and Technology, Trondheim, Norway1, Warwick-NTU Neuroscience programme, Nanyang Technological University, Singapore2, Warwick-NTU Neuroscience programme, University of Warwick, UK3 A fundamental goal of molecular neurophysiology is to understand cellular basis of ongoing neuronal activity in behaving animals. We have recently developed an approach to study local cellular mechanisms of hippocampal place cell activity without affecting animals' cognitive ability or behaviors, by combining microgenetic manipulations and targeted multi-tetrode recording. In this study, we devised viral vectors for RNA interference (RNAi) to make this approach versatile for examining the functions of any genes of interest. As a first application, we examined the roles of NMDA receptors which mediate several forms of synaptic plasticity. The NR1 gene encodes one of the subunits essential to form functional NMDA receptors. In vitro screening identified two shRNA sequences effectively suppressing NR1 expression. Efficacy of knockdown in the brain was estimated by c-fos expression, which depends on NMDA receptor activation. Either shRNA delivered locally into the rat hippocampal CA1 area by adeno-associated viral vector reduced c-fos positive cells, indicating the reduction in NMDA receptor function. By combining precisely targeted tetrode recordings, we monitored activity of place cells in the vector-infected CA1 area while animals actively foraged in environments. Preliminary results showed that NR1 knockdown impairs phase modulation of neuronal firing by local network oscillations, suggesting that NMDA receptor-dependent synaptic plasticity regulates temporal coding in CA1 place cells. Because RNAi is applicable for any genes, this approach enables us to investigate roles of various cellular mechanisms mediating specific patterns of neuronal activity in freely-behaving rodents.	P3-1-181 NTNGパラログによる認知機能サブドメインの分離 Cognitive subdomains function segregation among the human NTNG paralogs ○プロセルコフパベル1,2, 橋本亮太3,4, 大井一高4, 武田雅俊4, 糸原重美1 ○Pavel Prosselkov1,2, Ryota Hashimoto3,4, Kazutaka Ohi4, Masatoshi Takeda4, Shigeyoshi Itohara1 理化学研究所 脳科学総合研究センター 行動遺伝学技術開発チーム 神経回路遺伝学棟1, 東京大学大学院農学生命科学研究科獣医 学・応用動物科学専攻2, 大阪大院・連合小児発達・子どものこころ3, 大阪大院・医・精神医学4 Lab. Behavioral Genetics, RIKEN BSI, Saitama1, Vet Medicine, Grad School Agr Life Sci, Univ Tokyo, Tokyo2, Mol Res Cent, United Grad Sch of Child Dev, Osaka Univ, Suita3, Dept Psychiatry, Osaka Univ Grad Sch Med, Suita4 Originally derived from the cell adhesion (laminin) and guidance cue superfamilies (netrins), Netrin-G1and Netrin-G2 are unique in their ability to attach to the presynaptic membrane and their brain-restrictedappearance. Their self-exclusive pattern of expression in the brain areas and participation in the brainlaminar structure formation points to a discernable dissociation of their function in informationsegregation flows. Netrin-G1 and Netrin-G2 show an extraordinary level of protein conservation amongvertebrates, with 100% and 99% identity between humans and apes, 97% and 88% between mice andhumans, and 67% and 57% between humans and the tetrapod fish coelacanth. Two coding areas withinboth genes (Ukd domain and GPI-link) underwent accelerated evolution with the simultaneous greatexpansion of the preceeding introns. Single nucleotide substitutions within them seemed to have a keyrole in the Netrin-G subneofunctionalization and, as a result, adopting the de novo-evolving cognitivefeatures. To test this, schizophrenic patients (Netrin-G1: n=61, Netrin-G2: n=59, controls: n=143)carrying SNPs for either Netrin-G1 or Netrin-G2 genes underwent IQ tests (WAIS-III). The resultsunequivocally demonstrated the dramatic effect of a single SNP for each gene on the cognitivesubdomain performance with Netrin-G1 SNP affecting verbal comprehension (p = 0.0037) and Netrin-G2 affecting the working memory (p = 0.0031) information flows. Human psychogenetics data arecorroborated by the observations in the mouse cognitive phenotype abnormality, with Netrin-G2, but notNetrin-G1, upregulated by the cognitive task and a smaller brain size for the both KO mice upon lifetimeintensive cognitive training. Despite Netrin-G1 and Netrin-G2 having identical gene and protein domainstructures, their functions are definitely not the same, but rather complementary to each other,comprising the unit of cognition. Supported by FIRST Program (SI)
P3-1-182 仮想現実環境における記憶に基づく空間ナビゲーション課題 A memory-guided spatial navigation task in a virtual reality environment ○水田恒太郎1, 佐藤正晃1,2, 河野真子1, 林康紀1,3 ○Kotaro Mizuta1, Masaaki Sato1,2, Masako Kawano1, Yasunori Hayashi1,3 理研・BSI1, JSTさきがけ2, 埼玉大3 RIKEN BSI, Saitama, Japan1, JST PRESTO2, Saitma Univ., Saitama, Japan3 Virtual reality (VR) is becoming an increasingly important technology in investigating navigation-related neural activity such as place-specific firing of hippocampal neurons in head-fixed mice. However, it remains unclear whether the behavior of the mice is guided by their spatial memory when they navigate within a VR environment. To address this issue, we have developed a new spatial memory task that can be performed using our previously reported VR system (Sato et al., 35th Ann. Mtg. Jpn. Neurosci. Soc., P3-a32, 2012). In this task, mice start running from one end of a virtual linear track to seek for water rewards given at a target zone in the middle of the track. Varying black-and-white patterns on the walls and floor serve as proximal cues and a few large objects are put around the track as distal cues. Once mice reach the other end of the track, they are transferred to the start position for the next trial. This simple unidirectional task can minimize the training period and makes it possible for mice to run many trials within a session. Mice are usually trained for 15 min per session and 1-2 sessions a day. The whole training protocol consists of two phases: (1) Non-delayed task. In the first several sessions, mice are rewarded immediately whenever they enter and pass through the target zone. (2) Delayed task. In the following sessions, mice need to navigate visually to the same target and stay there for a sufficient period of time to get rewards. The trained mice showed steady increase in running speed, distance traveled and the number of rewards over the non-delayed phase. This indicates that they readily learn to run in this VR setting. When the delay was introduced, the number of rewards dropped but gradually increased again as they learned to stop and stay in the target in most trials. This VR task thus provides a new behavioral paradigm for studying plastic changes of hippocampal memory circuits with in vivo calcium imaging and electrophysiology.	P3-1-183 線虫C. elegansが背腹方向の濃度勾配を検出する機構の光遺伝学的解析 Optogenetic analysis of the mechanism for sensing dorso-ventral chemical gradients in C. elegans ○佐藤陽介1, 國友博文1, 飯野雄一1 ○Yohsuke Satoh1, Hirofumi Kunitomo1, Yuichi Iino1 東京大院・理・生物化学1 Dep. of Biophy. & Biochem., Grad. Sch. of Sci., Univ. of Tokyo1 Orientation behaviors are essential for survival in both highly evolved and simpler animals. C. elegans shows chemotaxis to various chemicals, using klinotaxis as one of its orientation mechanisms. In klinotaxis, the animal recognizes a dorso-ventral(D-V) chemical gradient during forward locomotion and gradually curves towards higher (or lower) concentrations. It is an interesting question how C. elegans recognizes such gradient and adjusts the behavior using its small number of neurons. Anterior chemosensory neurons are exposed to the environment only at the amphid sensilla located at the anterior tip of the body. It is therefore probable that the temporal pattern of chemosensory inputs related to head swing during undulatory locomotion is used to recognize the D-V chemical gradient. Thus, we planned to mimic sensory input and drive klinotaxis to determine the possible mechanism. We decided to activate each of ASE gustatory neurons (ASEL/R), both of which show calcium response to NaCl conc. changes, using ChR2 to manipulate sensory inputs. Since C. elegans memorizes NaCl conc.s and is attracted to the conc. at which it was previously cultivated, we performed the test on animals that experienced different NaCl conc.s. We photostimulated the neuron in synchrony with the sigmoidal locomotion, using a newly developed device that automatically photostimulates depending on the animal's body posture. This operation on ASER induced curving to both the stimulated side or the other side in an experience dependent manner. The operation on ASEL induced curving only to the stimulated side. These results indicate that integration of sensory and locomotory information is important for klinotaxis and that ASER and ASEL are involved in sensing D-V gradient in different manners. Our results also suggest that sensory information of NaCl conc. changes is integrated with NaCl conc. memory, in the neural circuit downstream of the cellular calcium signal in the ASE neurons.
P3-1-184 海馬歯状回特異的なNMDA受容体Mgブロックの解除によるパターン分離能の低下 Reduced Mg2+ Blockade of NMDAR in the Dentate Gyrus Impairs Pattern Separation of Hippocampal Place Representation ○林勇一郎1, 鍋島曜子2, 鍋島陽一2, 船曳和雄3 ○Yuichiro Hayashi1, Nabeshima Yoko2, Nabeshima Yo-Ichi2, Funabiki Kazuo3 京都大学大学院　医学研究科　メディカルイノベーションセンター1, 先端医療センター研究開発部門2, 大阪バイオサイエンス研究所3 Medical Innovation Center, Kyoto Univ Faculty of Medicine, Kyoto1, Institute for Biomedical Research and Innovation, Kobe, Japan2, Osaka Bioscience Institute, Osaka, Japan3 Voltage-dependent block of the NMDA receptor by Mg2+ is thought to be central to unique involvement of this receptor in higher brain functions. To directly test the role of the Mg2+ block in vivo, we devised a method to selectively induce a single amino acid substitution (N595Q) in the GluN2A subunit of the NMDA receptor only in the hippocampal dentate gyrus. CA1 cells in the mutants had normal size place field, but the fields were more stable than control and place fields for two different environments were more similar in the mutants. These results suggest that the intact Mg2+ block of the NMDA receptor in the dentate gyrus increases fluctuation of place representations in CA1, serving to separate multiple place representations.	P3-1-185 Crxノックアウトマウスを用いた感覚認知と学習の行動学的解析 Behavioral study of sensory perception and learning in visually impaired Crx knockout mice ○有働洋1, 井浦陽一郎1 ○Hiroshi Udo1, Youichiro Iura1 九州大学大学院 理学研究院 生物科学部門1 Dept Biol, Kyushu Univ1 Visual perception is critical for many animals and the loss of eyesight often causes devastating effects on their survival in natural environments. However, it may be compensated to some extent by utilizing other intact sensory systems. In this study, we analyzed the behavior of cone-rod homeobox knockout (Crx-/-) mice having visual impairment, using heterozygous knockout (Crx+/-) mice as controls. In the elevated plus maze test, we found that Crx-/- mice rarely fell from the platform to the same extent as Crx+/- mice. There was no reduction in the moving speed and the preference toward the closed arms, but the distance traveled during the test period was rather increased in Crx-/- mice. The open field test showed consistent results that there was no difference in thigmotaxis but the exploratory activity of Crx-/- mice was higher than Crx+/- mice. Since Crx-/- mice almost behaved similarly with Crx+/- mice except for their activities, we analyzed their vision with the glass table visual recognition test, Barnes maze with a visual cue, and light-dark transition test. All of these experiments indicated that Crx-/- mice indeed have visual impairment. We also found that -/- mice does not fall from the elevated platform when their whiskers were removed or earplugs were attached. In the fear conditioning test, Crx-/- mice were able to acquire contextual and cued memory to the same extent of Crx+/- mice. As a summary, these data suggest that blind Crx-/- mice are able to recognize external environment and learn by utilizing non-visual information.

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