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Increased activation of ventromedial prefrontal cortex during decision making in irritable bowel syndrome
e370
Abstracts / Neuroscience Research 71S (2011) e108–e415
P4-m05 SART stress decreases a capability of alveolar for natural immunity Chiyuki Wakaki , Yoshinori Funakami, Mariko Nakao, Daisuke Fukuda, Chisato Nishijima, Nozomi Tashiro, Akinori Kawaguchi, Hajime Asano, Takuma Iida, Risa Miyoshi, Tetsuyuki Wada, Seiji Ichida Div. Biochemistry, Sch. of Pharm., Kinki University, Osaka It has well known that potential for immunity in human body is decreased under a stress. While, macrophages (Ms) play an important role for immunoresponse. Cytokines are also affected by a stressed condition. The specific alternation of rhythm in temperature (SART) stress is one kind of environmental stress, induced by repeated sudden changes in ambient temperature. The SART-stressed animals are vagotonia-type autonomic imbalance model and have chronic stress symptoms. Therefore, it is supposed that the relationship between the autonomic nervous system, the endocrine system and the immune system breaks down in SART-stressed animals. In this work, to clear the relationships between stress and natural immunity, we investigated the change for immunoresponce in SART stressed mice using as an indicator for the number and the activity of alveolar Ms. Male ddY mice, weighing 20–30 g, were used. The bronchoalveolar lavage fluid (BALF) was obtained by washing lungs with phosphate-buffered saline under urethane anesthesia. Histological samples were prepared from mice lung after fixation by 4% paraformaldehyde perfusion. M fraction was obtained from the pellet by centrifugation of BALF. Number and phagocytotic activity of Ms in stressed group were significantly decreased in comparison with those in unstressed and cold stressed group. The amounts of inflammatory cytokines, IL-1, IL-6 and TNF-␣, in BALF were significantly reduced in the SARTstressed group. We obtained the similar result in the culture medium of Ms for 48 hours from the SART-stressed group, that is, the amounts of cytokines except IL-1 was reduced. Repeated oral administration of antianxiety drug, diazepam, attenuated the reduction of the number of M, phagocytotic activity and the amount of cytokines in BALF, which observed in the SART-stressed mice. These results suggest that the immune function in SART stressed mice under a repeated change in ambient temperature may be decreased. doi:10.1016/j.neures.2011.07.1623
P4-m06 Change of SART-stress induced c-Fos expression of hypothalamus in mice Takuma Iida 1 , Yoshinori Funakami 1 , Kengo Kurokawa 1 , Tomoyoshi Miyamoto 1 , Akiko Onabe 1 , Takayuki Kishi 1 , Sara Tanioka 1 , Maki Kishimoto 1 , Kazu Toyoda 1 , Yuri Taniguchi 1 , Akinori Kawaguchi 1 , Hajime Asano 1 , Chiyuki Wakaki 1 , Risa Miyoshi 1 , Tetsuyuki Wada 1 , Mamoru Nagano 2 , Yasufumi 2 1 Shigeyoshi , Seiji Ichida 1
Div. Biochem., Sch. Pharm., Kinki Univ., Osaka, Japan 2 Div. Anatomy and Neurobiology, Sch. Med., Kinki Univ., Osaka, Japan
When we are exposed to the steep change of ambient temperature every day for a long term, we sometimes develop various kinds of symptoms as a result of stress response. The specific alternation of rhythm in temperature (SART)-stressed animal has been prepared to simulate this stressful situation for ambient temperature. The stressed model animal is vagotonia-type autonomic imbalance model and has chronic stress symptoms. Therefore, it is considered that these abnormalities may be occurred as a result of imbalance of brain and autonomic function under the stressful condition. We studied the activity of nervous system for SART-stressed mice at each loaded period, especially that of in hypothalamus which plays an important role for the stress response and autonomic nervous system. The c-Fos expression was used as an indicator of neuronal activity. SART-stressed mice were induced by changes from 4 ◦ C to 24 ◦ C and then from 24 ◦ C to 4 ◦ C hourly during 10:00–16:00 in ambient temperature repeatedly for 7 days, and were used on the 8th day to experiment, in which the mice were kept at 24 ◦ C for at least 30 min after once change from 4 ◦ C to 24 ◦ C during 10:00–11:00 for 1 h. In the SART-stress loading at the beginning stage on the first day, the amount of c-Fos expression in paraventricular hypothalamic nucleus (PVN) and dorsomedial hypothalamic nucleus (DMH) was significantly increased. On the other hand, in the SART-stress loading on the third and 8th day, the amount of c-Fos expression decreased significantly in comparison with those on the first day. It has been reported that the area of PVN and DMH relates from the activity of autonomic nervous or endocrine system and from the activity of sympathetic nervous system, respectively. Therefore, from these results, it is considered that SART-stressed animals caused the abnormality such as an
imbalance of autonomic nervous system and chronic stress symptoms due to the decrease for neuronal response in PVN and DMH. doi:10.1016/j.neures.2011.07.1624
P4-m07 Analysis of neurotransmitters/neuromodulators released under low gravity using microdialysis technique Katarzyna A. Inoue 1 , Kimiya Narikiyo 2 , Jorge L. Zeredo 3 , Akira Masuda 2 , Shuji Aou 2 , Yasuhiro Kumei 1 1
Dept. Biochemistry, Tokyo Med. & Dent. University, Tokyo, Japan 2 Graduate School, Kyushu Institute of Technology, Kitakyushu, Japan 3 University of Brasilia, Brasilia, Brazil The hypothalamus is an important part of human and animal brain. It controls many autonomic functions of peripheral nerve system as well as regulates endocrine system hormones, thus maintaining body homeostasis. We have investigated low-gravity-dependent changes of local secretion of neurotransmitters in hypothalamic arcuate nucleus (ARC), by implementing a microdialysis technique combined with neuronal recording. Rats with implanted microdialysis probes were subjected to a series a low-gravity exposures of 0.3 G, 0.15 G, and 0.01 G, during parabolic flights. Samples were collected during four consecutive exposures to the same level of low-gravity. Simultaneously, electrical activity in the ARC was recorded via electrodes adjacent to the microdialysis probe. Analysis of the local concentrations of neurotransmitters showed an increase in the concentration of dopamine and a decrease in the concentrations of inhibitory neuromodulators such as serotonin and beta-endorphin. The neuronal spike activity showed an excitatory response to low-G levels, suggesting increased excitability of neurons within the rat’s ARC. Research fund: grants from JAXA and Japan Society for Promotion of Science to Y. Kumei. doi:10.1016/j.neures.2011.07.1625
P4-m08 Phasic dopamine responses during peak-interval task in mice Kenji Yoshimi 1 Kitazawa 1 1
, Shihoko Misawa 2 , Yasushi Shimo 2 , Shigeru
Juntendo University, School of Medicine 2 Dept. Neurology, Juntendo Univ
It has been reported that dopamine in the striatum plays a part in time estimation. We recorded dopamine release in the dorsomedial striatum of C57/BL6 mice during a peak interval task using fast-scan cyclic voltammetry (FSCV). Mice (n = 7) were trained to poke a hole 5 s after a cue onset for food reward. Phasic dopamine responses following the reward delivery were significant. Four of seven animals showed smaller but significant responses just after the cue-onset. However, in spite of clear increase of poking behaviors toward the target timing of 5 s, dopamine responses did not show significant increases before the reward delivery. Our results suggest that phasic dopamine neurotransmission was not a direct determinant of the poking behavior based on time prediction. Research fund: Strategic Research program for brain sciences (SRPBS) from MEXT. doi:10.1016/j.neures.2011.07.1626
P4-m09 Increased activation of ventromedial prefrontal cortex during decision making in irritable bowel syndrome Emiko Aizawa 1 , Takanori Kochiyama 2 , Yasuhiro Sato 3 , 1 Joe Morishita , Atsushi Sekiguchi 4 , Yuka Kotozaki 5 , Atsushi Miyazaki 6 , Michiko Kano 1 , Motoyori Kanazawa 1 , Motoaki 4 4,5 Sugiura , Ryuta Kawashima , Hajime Mushiake 6 , Shin Fukudo 1 1
Behavioral Medicine, Grad. Sch. of Med., Tohoku Univ., Sendai, Japan Advanced Telecommunications Research Institute International, Brain Activity Imaging Center, Kyoto, Japan 3 Psychosomatic Medicine, Tohoku Univ. of Hospital 4 Functional Brain Imaging, Institute of Development, Aging and Cancer, Tohoku Univ 5 Smart Ageing International Research Center, Institute of Development, Aging and Cancer, Tohoku Univ 6 Physiology, Grad. Sch. of Med., Tohoku Univ 2
Aim: Patients with irritable bowel syndrome (IBS) show exaggerated sensorimotor function of the gastrointestinal tract against stress. The IOWA Gambling Task (IGT) assesses decision making under initially ambiguous conditions. The somatic markers(SM) may be integrated automatically, involuntarily, and unconsciously by the ventromedial prefrontal cortex (vmPFC)
Abstracts / Neuroscience Research 71S (2011) e108–e415
into the more conscious decision making process. We hypothesized that brain processing in individuals with IBS, during decision making, is different from that of healthy controls (HC). The body signals of IBS are more active than that of HC, due to increased activity of vmPFC. Methods: Subjects were individuals with IBS (n = 30, aged 21.5) diagnosed with Rome III criteria. Age-, sex-, education and intelligence-matched HC (n = 30) were compared. Using PHILIPS 3.0T Scanner, event-related functional magnetic resonance imaging (fMRI) was performed to determine the specific location and pattern of activation in the brain during the IGT. Brain image was analyzed with statistical parametric mapping 8. We compared BOLD activity of the two groups during card selection in the decision-making and control task. Results: IBS subjects showed no difference in net scores. IBS subjects had significantly more one of advantageous card selections (p < 0.05) and gaining money (p < 0.05). Brain imaging data revealed that IBS subjects showed significantly less activity in the left anterior insula (p < 0.005) and significantly more activity in the right medial PFC (p < 0.005) during decision making conditions than HC. Conclusion: These findings suggest that individuals with IBS show advantageous decision making due to more activity of vmPFC. doi:10.1016/j.neures.2011.07.1627
P4-m10 Activation of dorsal raphe serotonin neurons is necessary for waiting for delayed rewards Kayoko Miyazaki , Katsuhiko Miyazaki, Kenji Doya Neural Computation Unit, OIST, Okinawa, Japan The forebrain serotonergic system is a crucial component in the control of impulsive behaviors. We previously showed by microdialysis that serotonin (5-HT) release increased when rats performed a delayed reward task and by electrode recording that dorsal raphe (DR) 5-HT neurons increase firing during reward waiting periods (Miyazaki et al., 2011). Here we test the causal relationship between 5-HT neural activity and tolerance for delayed reward. We locally appled 5-HT1A receptor agonist 8-OH-DPAT, which is known to suppress 5-HT neurons, in the DR nucleus using microdialysis (200 M, 2 l/min). In preparatory experiments using another microdialysis probe in the medial prefrontal cortex, we verified that 5-HT release was reduced by 40% during 8-OH-DPAT perfusion, showing the inhibition of DR 5-HT neuron activity. Rats (n = 5) performed a sequential food-water navigation task, which required them to visit two rewarding sites alternately, under two conditions: the short delayed reward condition in which a food pellet or a water spout was delivered after 2 seconds from the rats’ entry to the reward sites, and the long delayed reward condition in which the delay was increased to 7–11 s. We compared the number of total trials, choice errors (rat visited a wrong site) and wait errors (rat left the reward site prematurely) during 30 min task periods before, during, and after 8-OH-DPAT perfusion. In the long delayed condition, wait errors significantly increased (ANOVA, food site, p = 0.014; water site, p = 0.032) while total trials (food site, p = 0.44; water site, p = 0.053), and choice errors (food site, p = 0.25; water site, p = 0.49) did not significantly change. None of the scores significantly changed in the short delayed reward condition. The selective increase in the wait errors during the long delayed reward condition during 8-OH-DPAT perfusion suggests that activation of DR 5-HT neurons facilitates rats’ waiting behavior in prospect of forthcoming rewards. doi:10.1016/j.neures.2011.07.1628
P4-m11 Risk preference was affected by inactivation of rat anterior insular cortex and orbitofrontal cortex in the amount and delay gambling tasks Hironori Ishii , Shinya Ohara, Ken-Ichiro Tsutsui, Toshio Iijima Div. of Sytems Neurosci., Grad. Sch. of Lifesci., Tohoku Univ., Sendai, Japan How does our brain make decisions under risky conditions whose outcome can be either good or bad? Previous studies have found that orbitofrontal cortex (OFC) plays a key role in decision-making under risk. As patients with damage to OFC have more tendencies than normal subjects to take higher risk, it is considered that OFC is inhibiting the tendency to be overattracted by risky options. Recent human imaging studies have indicated that anterior insular cortex (AIC) is also activated in a gambling task as well as OFC. However, the role of AIC and its relationship with OFC in decision-making under risk are still unclear. In this study, we investigated the effects of inactivation of AIC and OFC on risk preference using rats. We used two types of gambling tasks. One was the amount gambling task which required the rats to choose between a variable amount (4 drops or no water) and a certain amount (x drops of water). The other was the delay gambling task which required to
e371
choose between a variable delay to get water (0 s or 10 s delay) and a certain delay (x s delay). By changing x in the certain option in these tasks, we examined the subjective equivalent point between risky and certain options. Then, we tested the effects of inactivation of AIC and OFC on this risk preference by injecting cocktail of muscimol and baclofen. Until now, we obtained preliminary result that preference for risky option decreased when AIC was inactivated and inactivation of OFC increased risk preference. These results suggest that AIC and OFC work oppositely in decision-making under risk. doi:10.1016/j.neures.2011.07.1629
P4-m12 Hippocampal theta rhythm related rewardexpectation in operant lever-press task Yuji Takano 1,2 , Masatoshi Ukezono 1,2,3 , Nobuaki Takahashi 1,2,4 , Naoyuki Hironaka 1,2 1
NTT Communication Science Laboratories, Kanagawa 2 CREST, JST Gakuin University, Tokyo 4 Kwansei Gakuin University, Hyogo
3
Meiji
The hippocampal theta rhythm is a sinusoidal-like wave at about 4–10 Hz in the local field potential recorded in the hippocampus. The theta rhythm has been thought to have important function in learning and memory. Recently, some studies suggest that the phase-locked theta is related with reward expectation. Then, we systematically examined the relationship between the hippocampal theta and reward expectation using operant lever-press task. We trained rats under one of the following 3 schedules for food reinforcement: Fixed Ratio (FR) 1, yoked control of FR1, FR1 with 2 sec-delay of food delivery. The hippocampal local filed potentials were recorded throughout the session. In FR1 schedule, the phase-locked theta appeared before leverpress action and disappeared after getting reward. In that of yoked control, the phase-locked theta appeared at the timing of dropping the reward. In FR1 schedule with 2 sec-delay, the phase-locked theta first appeared before and disappeared after lever-press action. But 2 sec later, it appeared again at the timing of dropping the reward. These results suggest that the phaselocked theta appeared at the start of action for reward and at appearance of reward. The function of the former would be reward expectation, and the latter would be attention. doi:10.1016/j.neures.2011.07.1630
P4-m13 Neuronal modulation in appetitive and aversive contexts in the primate lateral hypothalamus Atsushi Noritake 1 , Kae Nakamura 1,2 1
Physiol. of Kansai Med. Univ., Osaka, Japan Saitama, Japan
2
Jst, PRESTO, Kawaguchi,
To study how the lateral hypothalamus (LH) neurons process appetitive and/or aversive information, we recorded single-unit activity in the LH of two monkeys while they performed a Pavlovian conditioning task with two distinct contexts. In the appetitive block (APP), liquid reward or a tone was used whereas in the aversive block (AVE), an air-puff directed at the monkey face or a tone was used as unconditioned stimuli (US). In each block, there were uncued and cued trials. On the uncued trials, an US was delivered unpredictably. On the cued trials, after presentation of an alarming cue (1.2 s), one of three visual conditioned stimuli (CS) associated with the outcome with probabilities of 100, 50, and 0% respectively, was presented (1.0 s). A trace period (1.0 s) was followed by the delivery of USs. Among 246 task-related neurons, in the APP block, many neurons’ (n = 48) CS response was significantly modulated by the probability of upcoming rewards (p < .01); about half (n = 26) showed stronger activity for the CS associated with greater rewards whereas the other half (n = 22) showed stronger activity for the CS associated with less rewards. In contrast, only a few neurons (n = 9) showed modulation in the AVE block. We also found that, in the APP block, many neurons (n = 39) were modulated in US activity by their predictability indicated by CSs (100%, 50%, and uncued trials); about half (n = 18) responded more for predicted than unpredicted USs; the other half (n = 21) responded more for unpredicted than predicted USs. In the AVE block, only eight neurons showed modulation in response to the USs depending on their predictability. These results suggest that (1) The primate LH neurons process both appetitive and aversive information; (2) However, their response is modulated by the degree of probability and/or predictability of rewards only in the appetitive context. doi:10.1016/j.neures.2011.07.1631
Abstracts / Neuroscience Research 71S (2011) e108–e415
P4-m05 SART stress decreases a capability of alveolar for natural immunity Chiyuki Wakaki , Yoshinori Funakami, Mariko Nakao, Daisuke Fukuda, Chisato Nishijima, Nozomi Tashiro, Akinori Kawaguchi, Hajime Asano, Takuma Iida, Risa Miyoshi, Tetsuyuki Wada, Seiji Ichida Div. Biochemistry, Sch. of Pharm., Kinki University, Osaka It has well known that potential for immunity in human body is decreased under a stress. While, macrophages (Ms) play an important role for immunoresponse. Cytokines are also affected by a stressed condition. The specific alternation of rhythm in temperature (SART) stress is one kind of environmental stress, induced by repeated sudden changes in ambient temperature. The SART-stressed animals are vagotonia-type autonomic imbalance model and have chronic stress symptoms. Therefore, it is supposed that the relationship between the autonomic nervous system, the endocrine system and the immune system breaks down in SART-stressed animals. In this work, to clear the relationships between stress and natural immunity, we investigated the change for immunoresponce in SART stressed mice using as an indicator for the number and the activity of alveolar Ms. Male ddY mice, weighing 20–30 g, were used. The bronchoalveolar lavage fluid (BALF) was obtained by washing lungs with phosphate-buffered saline under urethane anesthesia. Histological samples were prepared from mice lung after fixation by 4% paraformaldehyde perfusion. M fraction was obtained from the pellet by centrifugation of BALF. Number and phagocytotic activity of Ms in stressed group were significantly decreased in comparison with those in unstressed and cold stressed group. The amounts of inflammatory cytokines, IL-1, IL-6 and TNF-␣, in BALF were significantly reduced in the SARTstressed group. We obtained the similar result in the culture medium of Ms for 48 hours from the SART-stressed group, that is, the amounts of cytokines except IL-1 was reduced. Repeated oral administration of antianxiety drug, diazepam, attenuated the reduction of the number of M, phagocytotic activity and the amount of cytokines in BALF, which observed in the SART-stressed mice. These results suggest that the immune function in SART stressed mice under a repeated change in ambient temperature may be decreased. doi:10.1016/j.neures.2011.07.1623
P4-m06 Change of SART-stress induced c-Fos expression of hypothalamus in mice Takuma Iida 1 , Yoshinori Funakami 1 , Kengo Kurokawa 1 , Tomoyoshi Miyamoto 1 , Akiko Onabe 1 , Takayuki Kishi 1 , Sara Tanioka 1 , Maki Kishimoto 1 , Kazu Toyoda 1 , Yuri Taniguchi 1 , Akinori Kawaguchi 1 , Hajime Asano 1 , Chiyuki Wakaki 1 , Risa Miyoshi 1 , Tetsuyuki Wada 1 , Mamoru Nagano 2 , Yasufumi 2 1 Shigeyoshi , Seiji Ichida 1
Div. Biochem., Sch. Pharm., Kinki Univ., Osaka, Japan 2 Div. Anatomy and Neurobiology, Sch. Med., Kinki Univ., Osaka, Japan
When we are exposed to the steep change of ambient temperature every day for a long term, we sometimes develop various kinds of symptoms as a result of stress response. The specific alternation of rhythm in temperature (SART)-stressed animal has been prepared to simulate this stressful situation for ambient temperature. The stressed model animal is vagotonia-type autonomic imbalance model and has chronic stress symptoms. Therefore, it is considered that these abnormalities may be occurred as a result of imbalance of brain and autonomic function under the stressful condition. We studied the activity of nervous system for SART-stressed mice at each loaded period, especially that of in hypothalamus which plays an important role for the stress response and autonomic nervous system. The c-Fos expression was used as an indicator of neuronal activity. SART-stressed mice were induced by changes from 4 ◦ C to 24 ◦ C and then from 24 ◦ C to 4 ◦ C hourly during 10:00–16:00 in ambient temperature repeatedly for 7 days, and were used on the 8th day to experiment, in which the mice were kept at 24 ◦ C for at least 30 min after once change from 4 ◦ C to 24 ◦ C during 10:00–11:00 for 1 h. In the SART-stress loading at the beginning stage on the first day, the amount of c-Fos expression in paraventricular hypothalamic nucleus (PVN) and dorsomedial hypothalamic nucleus (DMH) was significantly increased. On the other hand, in the SART-stress loading on the third and 8th day, the amount of c-Fos expression decreased significantly in comparison with those on the first day. It has been reported that the area of PVN and DMH relates from the activity of autonomic nervous or endocrine system and from the activity of sympathetic nervous system, respectively. Therefore, from these results, it is considered that SART-stressed animals caused the abnormality such as an
imbalance of autonomic nervous system and chronic stress symptoms due to the decrease for neuronal response in PVN and DMH. doi:10.1016/j.neures.2011.07.1624
P4-m07 Analysis of neurotransmitters/neuromodulators released under low gravity using microdialysis technique Katarzyna A. Inoue 1 , Kimiya Narikiyo 2 , Jorge L. Zeredo 3 , Akira Masuda 2 , Shuji Aou 2 , Yasuhiro Kumei 1 1
Dept. Biochemistry, Tokyo Med. & Dent. University, Tokyo, Japan 2 Graduate School, Kyushu Institute of Technology, Kitakyushu, Japan 3 University of Brasilia, Brasilia, Brazil The hypothalamus is an important part of human and animal brain. It controls many autonomic functions of peripheral nerve system as well as regulates endocrine system hormones, thus maintaining body homeostasis. We have investigated low-gravity-dependent changes of local secretion of neurotransmitters in hypothalamic arcuate nucleus (ARC), by implementing a microdialysis technique combined with neuronal recording. Rats with implanted microdialysis probes were subjected to a series a low-gravity exposures of 0.3 G, 0.15 G, and 0.01 G, during parabolic flights. Samples were collected during four consecutive exposures to the same level of low-gravity. Simultaneously, electrical activity in the ARC was recorded via electrodes adjacent to the microdialysis probe. Analysis of the local concentrations of neurotransmitters showed an increase in the concentration of dopamine and a decrease in the concentrations of inhibitory neuromodulators such as serotonin and beta-endorphin. The neuronal spike activity showed an excitatory response to low-G levels, suggesting increased excitability of neurons within the rat’s ARC. Research fund: grants from JAXA and Japan Society for Promotion of Science to Y. Kumei. doi:10.1016/j.neures.2011.07.1625
P4-m08 Phasic dopamine responses during peak-interval task in mice Kenji Yoshimi 1 Kitazawa 1 1
, Shihoko Misawa 2 , Yasushi Shimo 2 , Shigeru
Juntendo University, School of Medicine 2 Dept. Neurology, Juntendo Univ
It has been reported that dopamine in the striatum plays a part in time estimation. We recorded dopamine release in the dorsomedial striatum of C57/BL6 mice during a peak interval task using fast-scan cyclic voltammetry (FSCV). Mice (n = 7) were trained to poke a hole 5 s after a cue onset for food reward. Phasic dopamine responses following the reward delivery were significant. Four of seven animals showed smaller but significant responses just after the cue-onset. However, in spite of clear increase of poking behaviors toward the target timing of 5 s, dopamine responses did not show significant increases before the reward delivery. Our results suggest that phasic dopamine neurotransmission was not a direct determinant of the poking behavior based on time prediction. Research fund: Strategic Research program for brain sciences (SRPBS) from MEXT. doi:10.1016/j.neures.2011.07.1626
P4-m09 Increased activation of ventromedial prefrontal cortex during decision making in irritable bowel syndrome Emiko Aizawa 1 , Takanori Kochiyama 2 , Yasuhiro Sato 3 , 1 Joe Morishita , Atsushi Sekiguchi 4 , Yuka Kotozaki 5 , Atsushi Miyazaki 6 , Michiko Kano 1 , Motoyori Kanazawa 1 , Motoaki 4 4,5 Sugiura , Ryuta Kawashima , Hajime Mushiake 6 , Shin Fukudo 1 1
Behavioral Medicine, Grad. Sch. of Med., Tohoku Univ., Sendai, Japan Advanced Telecommunications Research Institute International, Brain Activity Imaging Center, Kyoto, Japan 3 Psychosomatic Medicine, Tohoku Univ. of Hospital 4 Functional Brain Imaging, Institute of Development, Aging and Cancer, Tohoku Univ 5 Smart Ageing International Research Center, Institute of Development, Aging and Cancer, Tohoku Univ 6 Physiology, Grad. Sch. of Med., Tohoku Univ 2
Aim: Patients with irritable bowel syndrome (IBS) show exaggerated sensorimotor function of the gastrointestinal tract against stress. The IOWA Gambling Task (IGT) assesses decision making under initially ambiguous conditions. The somatic markers(SM) may be integrated automatically, involuntarily, and unconsciously by the ventromedial prefrontal cortex (vmPFC)
Abstracts / Neuroscience Research 71S (2011) e108–e415
into the more conscious decision making process. We hypothesized that brain processing in individuals with IBS, during decision making, is different from that of healthy controls (HC). The body signals of IBS are more active than that of HC, due to increased activity of vmPFC. Methods: Subjects were individuals with IBS (n = 30, aged 21.5) diagnosed with Rome III criteria. Age-, sex-, education and intelligence-matched HC (n = 30) were compared. Using PHILIPS 3.0T Scanner, event-related functional magnetic resonance imaging (fMRI) was performed to determine the specific location and pattern of activation in the brain during the IGT. Brain image was analyzed with statistical parametric mapping 8. We compared BOLD activity of the two groups during card selection in the decision-making and control task. Results: IBS subjects showed no difference in net scores. IBS subjects had significantly more one of advantageous card selections (p < 0.05) and gaining money (p < 0.05). Brain imaging data revealed that IBS subjects showed significantly less activity in the left anterior insula (p < 0.005) and significantly more activity in the right medial PFC (p < 0.005) during decision making conditions than HC. Conclusion: These findings suggest that individuals with IBS show advantageous decision making due to more activity of vmPFC. doi:10.1016/j.neures.2011.07.1627
P4-m10 Activation of dorsal raphe serotonin neurons is necessary for waiting for delayed rewards Kayoko Miyazaki , Katsuhiko Miyazaki, Kenji Doya Neural Computation Unit, OIST, Okinawa, Japan The forebrain serotonergic system is a crucial component in the control of impulsive behaviors. We previously showed by microdialysis that serotonin (5-HT) release increased when rats performed a delayed reward task and by electrode recording that dorsal raphe (DR) 5-HT neurons increase firing during reward waiting periods (Miyazaki et al., 2011). Here we test the causal relationship between 5-HT neural activity and tolerance for delayed reward. We locally appled 5-HT1A receptor agonist 8-OH-DPAT, which is known to suppress 5-HT neurons, in the DR nucleus using microdialysis (200 M, 2 l/min). In preparatory experiments using another microdialysis probe in the medial prefrontal cortex, we verified that 5-HT release was reduced by 40% during 8-OH-DPAT perfusion, showing the inhibition of DR 5-HT neuron activity. Rats (n = 5) performed a sequential food-water navigation task, which required them to visit two rewarding sites alternately, under two conditions: the short delayed reward condition in which a food pellet or a water spout was delivered after 2 seconds from the rats’ entry to the reward sites, and the long delayed reward condition in which the delay was increased to 7–11 s. We compared the number of total trials, choice errors (rat visited a wrong site) and wait errors (rat left the reward site prematurely) during 30 min task periods before, during, and after 8-OH-DPAT perfusion. In the long delayed condition, wait errors significantly increased (ANOVA, food site, p = 0.014; water site, p = 0.032) while total trials (food site, p = 0.44; water site, p = 0.053), and choice errors (food site, p = 0.25; water site, p = 0.49) did not significantly change. None of the scores significantly changed in the short delayed reward condition. The selective increase in the wait errors during the long delayed reward condition during 8-OH-DPAT perfusion suggests that activation of DR 5-HT neurons facilitates rats’ waiting behavior in prospect of forthcoming rewards. doi:10.1016/j.neures.2011.07.1628
P4-m11 Risk preference was affected by inactivation of rat anterior insular cortex and orbitofrontal cortex in the amount and delay gambling tasks Hironori Ishii , Shinya Ohara, Ken-Ichiro Tsutsui, Toshio Iijima Div. of Sytems Neurosci., Grad. Sch. of Lifesci., Tohoku Univ., Sendai, Japan How does our brain make decisions under risky conditions whose outcome can be either good or bad? Previous studies have found that orbitofrontal cortex (OFC) plays a key role in decision-making under risk. As patients with damage to OFC have more tendencies than normal subjects to take higher risk, it is considered that OFC is inhibiting the tendency to be overattracted by risky options. Recent human imaging studies have indicated that anterior insular cortex (AIC) is also activated in a gambling task as well as OFC. However, the role of AIC and its relationship with OFC in decision-making under risk are still unclear. In this study, we investigated the effects of inactivation of AIC and OFC on risk preference using rats. We used two types of gambling tasks. One was the amount gambling task which required the rats to choose between a variable amount (4 drops or no water) and a certain amount (x drops of water). The other was the delay gambling task which required to
e371
choose between a variable delay to get water (0 s or 10 s delay) and a certain delay (x s delay). By changing x in the certain option in these tasks, we examined the subjective equivalent point between risky and certain options. Then, we tested the effects of inactivation of AIC and OFC on this risk preference by injecting cocktail of muscimol and baclofen. Until now, we obtained preliminary result that preference for risky option decreased when AIC was inactivated and inactivation of OFC increased risk preference. These results suggest that AIC and OFC work oppositely in decision-making under risk. doi:10.1016/j.neures.2011.07.1629
P4-m12 Hippocampal theta rhythm related rewardexpectation in operant lever-press task Yuji Takano 1,2 , Masatoshi Ukezono 1,2,3 , Nobuaki Takahashi 1,2,4 , Naoyuki Hironaka 1,2 1
NTT Communication Science Laboratories, Kanagawa 2 CREST, JST Gakuin University, Tokyo 4 Kwansei Gakuin University, Hyogo
3
Meiji
The hippocampal theta rhythm is a sinusoidal-like wave at about 4–10 Hz in the local field potential recorded in the hippocampus. The theta rhythm has been thought to have important function in learning and memory. Recently, some studies suggest that the phase-locked theta is related with reward expectation. Then, we systematically examined the relationship between the hippocampal theta and reward expectation using operant lever-press task. We trained rats under one of the following 3 schedules for food reinforcement: Fixed Ratio (FR) 1, yoked control of FR1, FR1 with 2 sec-delay of food delivery. The hippocampal local filed potentials were recorded throughout the session. In FR1 schedule, the phase-locked theta appeared before leverpress action and disappeared after getting reward. In that of yoked control, the phase-locked theta appeared at the timing of dropping the reward. In FR1 schedule with 2 sec-delay, the phase-locked theta first appeared before and disappeared after lever-press action. But 2 sec later, it appeared again at the timing of dropping the reward. These results suggest that the phaselocked theta appeared at the start of action for reward and at appearance of reward. The function of the former would be reward expectation, and the latter would be attention. doi:10.1016/j.neures.2011.07.1630
P4-m13 Neuronal modulation in appetitive and aversive contexts in the primate lateral hypothalamus Atsushi Noritake 1 , Kae Nakamura 1,2 1
Physiol. of Kansai Med. Univ., Osaka, Japan Saitama, Japan
2
Jst, PRESTO, Kawaguchi,
To study how the lateral hypothalamus (LH) neurons process appetitive and/or aversive information, we recorded single-unit activity in the LH of two monkeys while they performed a Pavlovian conditioning task with two distinct contexts. In the appetitive block (APP), liquid reward or a tone was used whereas in the aversive block (AVE), an air-puff directed at the monkey face or a tone was used as unconditioned stimuli (US). In each block, there were uncued and cued trials. On the uncued trials, an US was delivered unpredictably. On the cued trials, after presentation of an alarming cue (1.2 s), one of three visual conditioned stimuli (CS) associated with the outcome with probabilities of 100, 50, and 0% respectively, was presented (1.0 s). A trace period (1.0 s) was followed by the delivery of USs. Among 246 task-related neurons, in the APP block, many neurons’ (n = 48) CS response was significantly modulated by the probability of upcoming rewards (p < .01); about half (n = 26) showed stronger activity for the CS associated with greater rewards whereas the other half (n = 22) showed stronger activity for the CS associated with less rewards. In contrast, only a few neurons (n = 9) showed modulation in the AVE block. We also found that, in the APP block, many neurons (n = 39) were modulated in US activity by their predictability indicated by CSs (100%, 50%, and uncued trials); about half (n = 18) responded more for predicted than unpredicted USs; the other half (n = 21) responded more for unpredicted than predicted USs. In the AVE block, only eight neurons showed modulation in response to the USs depending on their predictability. These results suggest that (1) The primate LH neurons process both appetitive and aversive information; (2) However, their response is modulated by the degree of probability and/or predictability of rewards only in the appetitive context. doi:10.1016/j.neures.2011.07.1631