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Role of monkey prefrontal cortex in temporal processing
Abstracts / Neuroscience Research 58S (2007) S1–S244
P1-g47 Olfactory learning deficits and suppression of agerelated memory impairment by a mutation in chico, a Drosophila insulin receptor substrate Shintaro Naganos 1,2 , Minoru Saitoe 2 1 Tokyo Metropolitan University, Department of Biological Sciences, Tokyo, Japan; 2 Tokyo Metropolitan Institute for Neuroscience, Tokyo, Japan Age-related memory impairment (AMI) is a phenotype of brain aging. The molecular mechanisms underlying AMI remain elusive. Given that regulation of lifespan by insulin/insulin-like growth factor signaling (IIS) and intrinsic linkage between AMI and organismal aging, one candidate signaling pathway underlying AMI is IIS. Here, we show that chico, which mediates Drosophila IIS, plays an essential role in olfactory learning and AMI. We found that chico null mutants exhibit learning deficits after olfactory conditioning. In addition, chico null mutation suppresses AMI. In contrast to chico, increasing IIS activity in the mushroom bodies (MBs), structures important for olfactory memory and AMI, causes premature AMI. Inconsistent with previous study, however, chico mutation did not extend female lifespan in our w(CS) genetic background. These results separate the brain aging from the organismal aging and demonstrate a biological role of IIS in the MBs both for learning and for AMI.
S113
2 Effects of eye contact on social attention and their P1-h0 neural basis investigated by fNIRS and EEGs Tsuneyuki Kobayashi 1,2 , Mikinobu Takeuchi 1,3 , Koichi Takamoto 1 , Etsuro Hori 1,2 , Mie Matsui 2,4 , Akihiro Ishikawa 5 , Satoru Kohno 5,6 , Taketoshi Ono 1 , Hisao Nishijo 1,2 1 System of Emotional Science, University of Toyama, Toyama, Japan; 2 CREST, JST, Japan; 3 Department of Neurosurgery, University of Toyama, Toyama, Japan; 4 Department of Psychology, University Toyama, Toyama, Japan; 5 R&D Department, Medical System Division, Shimazu Co. Ltd., Kyoto, Japan; 6 Human Brain Research Center, Kyoto University, Kyoto, Japan We investigated effects of eye contact on social attention and their neural basis by functional near infrared spectroscopy (fNIRS) and EEGs. A facial stimulus with a gaze directing to the left or right side of a display was presented. The subjects were required to indicate the location of a target stimulus which appeared at the left or right side of the display after the facial stimulus. Response latency to detect the target was shorter when gaze direction and location of the target was congruent. Effect of the gaze direction was more prominent when a facial stimulus with eye contact was presented. Now we are analyzing fNIRS and EEG data during this task, and the results indicated some heterogeneity of the cortex in social attention. Research fund: CREST
P1-g48 The relation of the spatial cognition deficit and the hippocampal heterotopic neurons in the prenatal MAM-treated rats Hideaki Imai, Kouzo Sugioka, Toshio Terashima Department of Anatomy and Developmental Neurobiology, Kobe University Graduate School of Medicine, Kobe, Japan Offspring resulting from prenatal exposure to Methylazoxymethanol (MAM), a DNA methylating agent, on the embryonic day 15 are characterized by malformations in hippocampus, loss of lamination in neocortex, and microcephaly. We had reported that MAM-treated rats showed impaired reference memory in Morris water maze during adult period. In this study, we estimated reference- and working-memory of MAM-treated rats during weaning period, using Morris water maze task (Stage 1) and delayed-matching-to-place (DMTP) task (Stage 2). We further examined whether heterotopic neurons in hippocampus and neocortex have normal neural network, by injection of FluoroGold (FG) into septum and cervical spinal cord. MAM-treated group showed significantly longer escape latency in Stage 1 and lower correct response ratio in Stage 2 than control. Also, FG-labeled neurons were observed in both heterotopic regions. These results suggest that spatial cognition deficit in MAM-treated rat could not result from functional decline of heterotopic neurons.
3 Behavioral paradigm for neurophysiological studies of P1-h0 metamemory in monkeys Akio Tanaka, Shintaro Funahashi Graduate School of Human and Environmental Studies, Kyoto University, Kyoto, Japan Recent behavioral studies have demonstrated that macaque monkeys possess the metamnemonic ability to monitor their own memory. In addition, recent neuropsychological as well as neuroimaging studies have revealed prefrontal contributions to metamemory. However, neural mechanisms underlying metamemory is not yet known. Therefore, we developed a behavioral paradigm that requires the ability of metamemory, using oculomotor delayed matching-to-sample tasks, in order to examine the neural mechanisms underlying metamemory in the prefrontal cortex. In this paradigm, monkeys are sometimes allowed to decide whether or not to take a test on their own, depending upon their own cognitive states, and are sometimes forced to take a test. Better performance on voluntarily taken than on forced tests indicates the metamnemonic ability in monkeys. We argue that the present paradigm can be an effective tool for examining neuronal substrates of metamemory through single-unit recordings in monkeys. Research fund: KAKENHI (17300103)
1 Role of monkey prefrontal cortex in temporal processP1-h0 ing Naosugi Yumoto 1 , Xiaofeng Lu 2 , Shigehiro Miyachi 3 , Atsushi Nambu 4 , Tomoki Fukai 5 , Masahiko Takada 1 1 Tokyo Metropolitan Institute for Neuroscience, Fuchu, Japan; 2 Juntendo University, Tokyo, Japan; 3 Primate Research Institute, Kyoto University, Kyoto, Japan; 4 National Institute for Physiological Sciences, Okazaki, Japan; 5 RIKEN, Wako, Japan To examine how the brain represents the length of the elapsed time, we devised a time-reproducing task. The task required a monkey to plan button press based on the estimates of the elapsed time. After the monkey became able to discriminate among several different time lengths (1 and 5 s for monkey M; 2, 4 and 7 s for monkey J), single neuron recording was performed in the prefrontal cortex, chiefly in area 9. We found that a group of cells displayed time length-specific activity. Further, we inactivated area 9 by injecting a small amount of muscimol (a GABA agonist). After the injections, the number of errors increased significantly during the performance of the task. These results indicate that area 9 plays a critical role in the temporal processing.
4 Dopamine responses to complex reward-predicting P1-h0 stimuli
Kensaku Nomoto 1,2 , Takeo Watanabe 3 , Masamichi Sakagami 1 Brain Research Science Center, Tamagawa University, Japan; 2 Department of Psychiatry, University of Tokyo, Japan; 3 Department of Psychology, Boston University, USA
1
Midbrain dopamine neurons (DA) are suggested to encode reward prediction error signals. Previous studies found that the DA discriminated reward-predicting stimuli from nonreward-predicting stimuli with 50–110 ms latency. However, it still remains unclear whether and how the DA respond to complex reward-predicting stimuli, which take time to discriminate. To examine this issue, we used random dot motion direction as reward-indicating stimulus feature, which is believed to require cortical processing, and recorded the DA activity of two Japanese monkeys when they performed random dot motion discrimination task with asymmetric reward schedule. We found that the asymmetric reward schedule modulated their task performance. Furthermore, the reward asymmetry did not affect the early component of the DA responses, but did the late component. Thus, we concluded that the DA calculated prediction errors based on continuously incoming information available at the moment. Research fund: Human Frontier Science Program
P1-g47 Olfactory learning deficits and suppression of agerelated memory impairment by a mutation in chico, a Drosophila insulin receptor substrate Shintaro Naganos 1,2 , Minoru Saitoe 2 1 Tokyo Metropolitan University, Department of Biological Sciences, Tokyo, Japan; 2 Tokyo Metropolitan Institute for Neuroscience, Tokyo, Japan Age-related memory impairment (AMI) is a phenotype of brain aging. The molecular mechanisms underlying AMI remain elusive. Given that regulation of lifespan by insulin/insulin-like growth factor signaling (IIS) and intrinsic linkage between AMI and organismal aging, one candidate signaling pathway underlying AMI is IIS. Here, we show that chico, which mediates Drosophila IIS, plays an essential role in olfactory learning and AMI. We found that chico null mutants exhibit learning deficits after olfactory conditioning. In addition, chico null mutation suppresses AMI. In contrast to chico, increasing IIS activity in the mushroom bodies (MBs), structures important for olfactory memory and AMI, causes premature AMI. Inconsistent with previous study, however, chico mutation did not extend female lifespan in our w(CS) genetic background. These results separate the brain aging from the organismal aging and demonstrate a biological role of IIS in the MBs both for learning and for AMI.
S113
2 Effects of eye contact on social attention and their P1-h0 neural basis investigated by fNIRS and EEGs Tsuneyuki Kobayashi 1,2 , Mikinobu Takeuchi 1,3 , Koichi Takamoto 1 , Etsuro Hori 1,2 , Mie Matsui 2,4 , Akihiro Ishikawa 5 , Satoru Kohno 5,6 , Taketoshi Ono 1 , Hisao Nishijo 1,2 1 System of Emotional Science, University of Toyama, Toyama, Japan; 2 CREST, JST, Japan; 3 Department of Neurosurgery, University of Toyama, Toyama, Japan; 4 Department of Psychology, University Toyama, Toyama, Japan; 5 R&D Department, Medical System Division, Shimazu Co. Ltd., Kyoto, Japan; 6 Human Brain Research Center, Kyoto University, Kyoto, Japan We investigated effects of eye contact on social attention and their neural basis by functional near infrared spectroscopy (fNIRS) and EEGs. A facial stimulus with a gaze directing to the left or right side of a display was presented. The subjects were required to indicate the location of a target stimulus which appeared at the left or right side of the display after the facial stimulus. Response latency to detect the target was shorter when gaze direction and location of the target was congruent. Effect of the gaze direction was more prominent when a facial stimulus with eye contact was presented. Now we are analyzing fNIRS and EEG data during this task, and the results indicated some heterogeneity of the cortex in social attention. Research fund: CREST
P1-g48 The relation of the spatial cognition deficit and the hippocampal heterotopic neurons in the prenatal MAM-treated rats Hideaki Imai, Kouzo Sugioka, Toshio Terashima Department of Anatomy and Developmental Neurobiology, Kobe University Graduate School of Medicine, Kobe, Japan Offspring resulting from prenatal exposure to Methylazoxymethanol (MAM), a DNA methylating agent, on the embryonic day 15 are characterized by malformations in hippocampus, loss of lamination in neocortex, and microcephaly. We had reported that MAM-treated rats showed impaired reference memory in Morris water maze during adult period. In this study, we estimated reference- and working-memory of MAM-treated rats during weaning period, using Morris water maze task (Stage 1) and delayed-matching-to-place (DMTP) task (Stage 2). We further examined whether heterotopic neurons in hippocampus and neocortex have normal neural network, by injection of FluoroGold (FG) into septum and cervical spinal cord. MAM-treated group showed significantly longer escape latency in Stage 1 and lower correct response ratio in Stage 2 than control. Also, FG-labeled neurons were observed in both heterotopic regions. These results suggest that spatial cognition deficit in MAM-treated rat could not result from functional decline of heterotopic neurons.
3 Behavioral paradigm for neurophysiological studies of P1-h0 metamemory in monkeys Akio Tanaka, Shintaro Funahashi Graduate School of Human and Environmental Studies, Kyoto University, Kyoto, Japan Recent behavioral studies have demonstrated that macaque monkeys possess the metamnemonic ability to monitor their own memory. In addition, recent neuropsychological as well as neuroimaging studies have revealed prefrontal contributions to metamemory. However, neural mechanisms underlying metamemory is not yet known. Therefore, we developed a behavioral paradigm that requires the ability of metamemory, using oculomotor delayed matching-to-sample tasks, in order to examine the neural mechanisms underlying metamemory in the prefrontal cortex. In this paradigm, monkeys are sometimes allowed to decide whether or not to take a test on their own, depending upon their own cognitive states, and are sometimes forced to take a test. Better performance on voluntarily taken than on forced tests indicates the metamnemonic ability in monkeys. We argue that the present paradigm can be an effective tool for examining neuronal substrates of metamemory through single-unit recordings in monkeys. Research fund: KAKENHI (17300103)
1 Role of monkey prefrontal cortex in temporal processP1-h0 ing Naosugi Yumoto 1 , Xiaofeng Lu 2 , Shigehiro Miyachi 3 , Atsushi Nambu 4 , Tomoki Fukai 5 , Masahiko Takada 1 1 Tokyo Metropolitan Institute for Neuroscience, Fuchu, Japan; 2 Juntendo University, Tokyo, Japan; 3 Primate Research Institute, Kyoto University, Kyoto, Japan; 4 National Institute for Physiological Sciences, Okazaki, Japan; 5 RIKEN, Wako, Japan To examine how the brain represents the length of the elapsed time, we devised a time-reproducing task. The task required a monkey to plan button press based on the estimates of the elapsed time. After the monkey became able to discriminate among several different time lengths (1 and 5 s for monkey M; 2, 4 and 7 s for monkey J), single neuron recording was performed in the prefrontal cortex, chiefly in area 9. We found that a group of cells displayed time length-specific activity. Further, we inactivated area 9 by injecting a small amount of muscimol (a GABA agonist). After the injections, the number of errors increased significantly during the performance of the task. These results indicate that area 9 plays a critical role in the temporal processing.
4 Dopamine responses to complex reward-predicting P1-h0 stimuli
Kensaku Nomoto 1,2 , Takeo Watanabe 3 , Masamichi Sakagami 1 Brain Research Science Center, Tamagawa University, Japan; 2 Department of Psychiatry, University of Tokyo, Japan; 3 Department of Psychology, Boston University, USA
1
Midbrain dopamine neurons (DA) are suggested to encode reward prediction error signals. Previous studies found that the DA discriminated reward-predicting stimuli from nonreward-predicting stimuli with 50–110 ms latency. However, it still remains unclear whether and how the DA respond to complex reward-predicting stimuli, which take time to discriminate. To examine this issue, we used random dot motion direction as reward-indicating stimulus feature, which is believed to require cortical processing, and recorded the DA activity of two Japanese monkeys when they performed random dot motion discrimination task with asymmetric reward schedule. We found that the asymmetric reward schedule modulated their task performance. Furthermore, the reward asymmetry did not affect the early component of the DA responses, but did the late component. Thus, we concluded that the DA calculated prediction errors based on continuously incoming information available at the moment. Research fund: Human Frontier Science Program