- Email: [email protected]
Roles of retinoic acid signaling pathway in emotional behavior
e270
Abstracts / Neuroscience Research 71S (2011) e108–e415
rons in the amygdala anatomically project to the DMM. Therefore, in the present study, the effects of 5-HT1 and 5-HT2 receptors in the amygdala on breathing were investigated using a microdialysis technique and a doublechamber plethysmograph. Adult male mice (C57BL/6N) were anesthetized intraperitoneally with sodium pentobarbital and locally with 0.5% Marcaine. A microdialysis probe was inserted into the amygdala. After the mice had recovered from anesthesia and acclimatized to the chamber, respiratory curves were recorded in a control (artificial cerebrospinal fluid perfusion) group, a 5-HT1 antagonist (10−5 M WAY-100635 perfusion) group, and a 5HT2 antagonist (10−5 M LY-53857 perfusion) group. Respiratory variables, such as respiratory rate, tidal volume and minute ventilation, were analyzed. After the experiments, microdialysis probe placement sites were verified in 50-m-thick coronal sections. 5-HT acting on 5-HT2 receptors in the DMM played a role in an increase in the frequency of basal breathing. The effects of 5-HT input in the amygdala region on breathing were analyzed. Based on the results, we discuss the effects of 5-HT input to the amygdala on breathing, and the possibility of emotional inhibitory input from the amygdala to the nTS. doi:10.1016/j.neures.2011.07.1178
P3-m16 Response patterns of primate orbitofrontal neurons and preference for visual stimuli Mika Takebayashi 1 , Shintaro Funahashi 1,2 1
Grad. Sch. of Human & Envrm. Std., Univ. of Kyoto, Kyoto 2 Kokoro Research Center, Univ. of Kyoto, Kyoto Positive emotion such as pleasant feeling can be produced by non-biological stimuli. In our previous study, we could determine monkeys’ preference for fractal stimuli by rank orders estimated by the preference comparison task. To explain the presence of monkeys’ preference for fractal stimuli, we hypothesized that observed rank order is based on the difference of the strength of the positive feeling when monkeys saw each fractal stimulus. Since the orbitofrontal cortex (OFC) has been known to participate in positive emotion, in the present experiment, we examined whether OFC activities encode information regarding the preference of fractal stimuli or not. We selected 70 fractal stimuli from 210 stimuli used in our behavioral study. These included 20 from preferred group, 20 from non-preferred group, and 30 from neutral group. Stimuli were randomly selected and presented for 0.5 s while monkeys looked at the fixation point. We recorded activities of 273 OFC neurons. We first examined whether a neuron responded particular stimuli or not. Responses magnitude varied greatly depending on a stimulus presented and each neuron exhibited different stimulus selectivity. However, when we compared averaged responses among 3 stimulus groups with different preferences, 23 neurons (15%) showed differential responses based on the difference of the stimulus preference. Differential responses were observed either during stimulus presentation, fixation after stimulus presentation, or reward period. Many of these neurons exhibited stronger response to either preferred or non-preferred stimuli. These results indicate that activities of OFC neurons encode information regarding the preference for visual stimuli. Research fund: KAKENHI 17300103, 20650073. doi:10.1016/j.neures.2011.07.1179
P3-m17 Methyl donor deficient diet during the developmental period changes gene expressions patterns of NMDA receptor subtypes in adults Daisuke Ishii , Daisuke Matsuzawa, Shingo Matsuda, Haruna Tomizawa, Chihiro Sutoh, Eiji Shimizu Dept Integrative Neurophysiol, Univ of Chiba, Chiba DNA methylation is one of the essential factors in the control of the gene expression. Nutrients related to one-carbon metabolism are known to play as an important mediator in transferring methyl groups for DNA methylation. Previous studies have shown that the long-term administration of a diet lacking essential one-carbon nutrients, methionine, choline and folic acid (methyl donor), caused global DNA hypermethylation in the brain. However, there has been no study that investigated the effects of a diet lacking methyl donors during the developmental period on the emotion of anxiety and fear. We examined behavioral alterations (anxiety-like behavior, contextual fear conditioning and extinction) in mice after exposing dietary deficiency in essential methyl donor during a certain period of development. We found that a methyl donor deficient diet increased anxiety and enhanced extinction of the contextual fear memory. Moreover, feeding mice with a methyl donor deficient diet resulted in significant changes in gene expres-
sions of NMDA receptor subtypes in adults. Our data suggested that the one-carbon metabolic pathway in the developmental brain was associated with increased anxiety and enhanced fear extinction in adults. doi:10.1016/j.neures.2011.07.1180
P3-m18 Roles of retinoic acid signaling pathway in emotional behavior Kaori Saito 1 Kida 1,2
, Masanori Nomoto 1,2 , Shusaku Uchida 1 , Satoshi
1
Dept. of Bioscience, Tokyo Univ. of Agriculture, Tokyo, Japan 2 CREST, JST, Saitama, Japan Retinoic acid (RA), a metabolite of Vitamin A, acts as a specific ligand for retinoic acid receptors (RARs). RARs function by forming a heterodimer with retinoid X receptor (RXR) and regulate various biological phenomena through transcriptional regulation. Importantly, RARs highly and ubiquitously express in the brain. Previous studies reported that RARbeta/RXRgamma double-knockout mice display a decrease in expression of dopamine D2 receptor in the striatum and a deficit in locomotor activity (Krezel et al., 1998), suggesting that RARs may play important roles in emotional behavior. In this study, to understand roles of RARs in emotional behaviors, we examined effects of loss-of-RARs function on emotional behaviors by analyzing conditional mutant mice that show forebrain-specific expression of dominant negative mutant of RARalpha (dnRAR) using a tetracycline-dependent transgene expression system. These mutant mice displayed a significant decrease in locomotor activity compared to control groups in the open field test. In the social interaction test, these mutant mice displayed a significant increase in social interaction time with a novel juvenile mouse compared to control groups, indicating that dnRAR mice exhibit abnormal social behavior. Furthermore, in forced swim and tail suspension tests, dnRAR mice displayed significant decreases in immobility time compared to control groups, suggesting that dnRAR mice exhibit manialike behaviors. Taken together, these observations suggest that dysfunction of RARs-signaling pathway in the forebrain leads to abnormal emotional behaviors and that RAR-signaling pathway in the forebrain contributes to regulation of emotional behaviors. Research fund: CREST Grant-in-Aid for Scientific Research (B) 20380078. doi:10.1016/j.neures.2011.07.1181
P3-m19 The sex differences in recovery of fear memory Shingo Matsuda , Daisuke Matuzawa, Daisuke Ishii, Haruna Tomizawa, Chihiro Sutoh, Ken Nakazawa, Eiji Shimizu Div. of Dev. Behavioral Cognitive Physiology, Grad. Sch. of Med., Chiba Univ., Chiba, Japan Objectives: Stress-related disorders including major depression and anxiety disorders are disproportionately prevalent in women. Posttraumatic stress disorder (PTSD) is repeatedly found to be more common among women than men. To investigate the mechanisms for these sex differences at the biological level, we examined contextual fear conditioning and extinction paradigm in mice. Methods: Twenty four C57BL/6J mice at 15 weeks of age (male:female = 12:12) were housed in group of three per cage. On day 1, mice were placed in conditioning chambers. On day 3 (conditioning phase), mice were received three US (footshocks). On day 4 (test phase), mice were placed into the chamber. On day 6–10 (extinction phase 1–5), mice were placed into the chamber. On day 31 (recall phase), mice were re-placed into the chamber. Results and discussion: Although female mice showed significant higher freezing responses than male mice in conditioning phase (p < 0.01), both male and female mice showed no significant freezing responses in test and extinction phases. Female mice in recall phase showed significant higher freezing responses than in extinction phase 5 (p < 0.05), but male mice did not. In addition, female mice showed significant higher freezing responses than male mice in recall phase (p < 0.05). On the other hand, female mice in recall phase showed significant lower freezing responses than in test phase (p < 0.01). These results suggested that female mice might have more persistent fear memory than male. doi:10.1016/j.neures.2011.07.1182
Abstracts / Neuroscience Research 71S (2011) e108–e415
rons in the amygdala anatomically project to the DMM. Therefore, in the present study, the effects of 5-HT1 and 5-HT2 receptors in the amygdala on breathing were investigated using a microdialysis technique and a doublechamber plethysmograph. Adult male mice (C57BL/6N) were anesthetized intraperitoneally with sodium pentobarbital and locally with 0.5% Marcaine. A microdialysis probe was inserted into the amygdala. After the mice had recovered from anesthesia and acclimatized to the chamber, respiratory curves were recorded in a control (artificial cerebrospinal fluid perfusion) group, a 5-HT1 antagonist (10−5 M WAY-100635 perfusion) group, and a 5HT2 antagonist (10−5 M LY-53857 perfusion) group. Respiratory variables, such as respiratory rate, tidal volume and minute ventilation, were analyzed. After the experiments, microdialysis probe placement sites were verified in 50-m-thick coronal sections. 5-HT acting on 5-HT2 receptors in the DMM played a role in an increase in the frequency of basal breathing. The effects of 5-HT input in the amygdala region on breathing were analyzed. Based on the results, we discuss the effects of 5-HT input to the amygdala on breathing, and the possibility of emotional inhibitory input from the amygdala to the nTS. doi:10.1016/j.neures.2011.07.1178
P3-m16 Response patterns of primate orbitofrontal neurons and preference for visual stimuli Mika Takebayashi 1 , Shintaro Funahashi 1,2 1
Grad. Sch. of Human & Envrm. Std., Univ. of Kyoto, Kyoto 2 Kokoro Research Center, Univ. of Kyoto, Kyoto Positive emotion such as pleasant feeling can be produced by non-biological stimuli. In our previous study, we could determine monkeys’ preference for fractal stimuli by rank orders estimated by the preference comparison task. To explain the presence of monkeys’ preference for fractal stimuli, we hypothesized that observed rank order is based on the difference of the strength of the positive feeling when monkeys saw each fractal stimulus. Since the orbitofrontal cortex (OFC) has been known to participate in positive emotion, in the present experiment, we examined whether OFC activities encode information regarding the preference of fractal stimuli or not. We selected 70 fractal stimuli from 210 stimuli used in our behavioral study. These included 20 from preferred group, 20 from non-preferred group, and 30 from neutral group. Stimuli were randomly selected and presented for 0.5 s while monkeys looked at the fixation point. We recorded activities of 273 OFC neurons. We first examined whether a neuron responded particular stimuli or not. Responses magnitude varied greatly depending on a stimulus presented and each neuron exhibited different stimulus selectivity. However, when we compared averaged responses among 3 stimulus groups with different preferences, 23 neurons (15%) showed differential responses based on the difference of the stimulus preference. Differential responses were observed either during stimulus presentation, fixation after stimulus presentation, or reward period. Many of these neurons exhibited stronger response to either preferred or non-preferred stimuli. These results indicate that activities of OFC neurons encode information regarding the preference for visual stimuli. Research fund: KAKENHI 17300103, 20650073. doi:10.1016/j.neures.2011.07.1179
P3-m17 Methyl donor deficient diet during the developmental period changes gene expressions patterns of NMDA receptor subtypes in adults Daisuke Ishii , Daisuke Matsuzawa, Shingo Matsuda, Haruna Tomizawa, Chihiro Sutoh, Eiji Shimizu Dept Integrative Neurophysiol, Univ of Chiba, Chiba DNA methylation is one of the essential factors in the control of the gene expression. Nutrients related to one-carbon metabolism are known to play as an important mediator in transferring methyl groups for DNA methylation. Previous studies have shown that the long-term administration of a diet lacking essential one-carbon nutrients, methionine, choline and folic acid (methyl donor), caused global DNA hypermethylation in the brain. However, there has been no study that investigated the effects of a diet lacking methyl donors during the developmental period on the emotion of anxiety and fear. We examined behavioral alterations (anxiety-like behavior, contextual fear conditioning and extinction) in mice after exposing dietary deficiency in essential methyl donor during a certain period of development. We found that a methyl donor deficient diet increased anxiety and enhanced extinction of the contextual fear memory. Moreover, feeding mice with a methyl donor deficient diet resulted in significant changes in gene expres-
sions of NMDA receptor subtypes in adults. Our data suggested that the one-carbon metabolic pathway in the developmental brain was associated with increased anxiety and enhanced fear extinction in adults. doi:10.1016/j.neures.2011.07.1180
P3-m18 Roles of retinoic acid signaling pathway in emotional behavior Kaori Saito 1 Kida 1,2
, Masanori Nomoto 1,2 , Shusaku Uchida 1 , Satoshi
1
Dept. of Bioscience, Tokyo Univ. of Agriculture, Tokyo, Japan 2 CREST, JST, Saitama, Japan Retinoic acid (RA), a metabolite of Vitamin A, acts as a specific ligand for retinoic acid receptors (RARs). RARs function by forming a heterodimer with retinoid X receptor (RXR) and regulate various biological phenomena through transcriptional regulation. Importantly, RARs highly and ubiquitously express in the brain. Previous studies reported that RARbeta/RXRgamma double-knockout mice display a decrease in expression of dopamine D2 receptor in the striatum and a deficit in locomotor activity (Krezel et al., 1998), suggesting that RARs may play important roles in emotional behavior. In this study, to understand roles of RARs in emotional behaviors, we examined effects of loss-of-RARs function on emotional behaviors by analyzing conditional mutant mice that show forebrain-specific expression of dominant negative mutant of RARalpha (dnRAR) using a tetracycline-dependent transgene expression system. These mutant mice displayed a significant decrease in locomotor activity compared to control groups in the open field test. In the social interaction test, these mutant mice displayed a significant increase in social interaction time with a novel juvenile mouse compared to control groups, indicating that dnRAR mice exhibit abnormal social behavior. Furthermore, in forced swim and tail suspension tests, dnRAR mice displayed significant decreases in immobility time compared to control groups, suggesting that dnRAR mice exhibit manialike behaviors. Taken together, these observations suggest that dysfunction of RARs-signaling pathway in the forebrain leads to abnormal emotional behaviors and that RAR-signaling pathway in the forebrain contributes to regulation of emotional behaviors. Research fund: CREST Grant-in-Aid for Scientific Research (B) 20380078. doi:10.1016/j.neures.2011.07.1181
P3-m19 The sex differences in recovery of fear memory Shingo Matsuda , Daisuke Matuzawa, Daisuke Ishii, Haruna Tomizawa, Chihiro Sutoh, Ken Nakazawa, Eiji Shimizu Div. of Dev. Behavioral Cognitive Physiology, Grad. Sch. of Med., Chiba Univ., Chiba, Japan Objectives: Stress-related disorders including major depression and anxiety disorders are disproportionately prevalent in women. Posttraumatic stress disorder (PTSD) is repeatedly found to be more common among women than men. To investigate the mechanisms for these sex differences at the biological level, we examined contextual fear conditioning and extinction paradigm in mice. Methods: Twenty four C57BL/6J mice at 15 weeks of age (male:female = 12:12) were housed in group of three per cage. On day 1, mice were placed in conditioning chambers. On day 3 (conditioning phase), mice were received three US (footshocks). On day 4 (test phase), mice were placed into the chamber. On day 6–10 (extinction phase 1–5), mice were placed into the chamber. On day 31 (recall phase), mice were re-placed into the chamber. Results and discussion: Although female mice showed significant higher freezing responses than male mice in conditioning phase (p < 0.01), both male and female mice showed no significant freezing responses in test and extinction phases. Female mice in recall phase showed significant higher freezing responses than in extinction phase 5 (p < 0.05), but male mice did not. In addition, female mice showed significant higher freezing responses than male mice in recall phase (p < 0.05). On the other hand, female mice in recall phase showed significant lower freezing responses than in test phase (p < 0.01). These results suggested that female mice might have more persistent fear memory than male. doi:10.1016/j.neures.2011.07.1182