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Orexin 2 receptor positively regulates the activity of orexin neurons
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Abstracts / Neuroscience Research 68S (2010) e55–e108
responses of the basal forebrain neurons may predict the future cognitive performance.
O1-9-4-1 Sex difference in the neural basis of parental bonding
doi:10.1016/j.neures.2010.07.108
Shota Nishitani , Tsunehiko Takamura, Sho Yamashita, Kazuyuki Shinohara
O1-9-3-3 Loss of Goosecoid-like and Dgcr14 in interpeduncular nucleus alters the expression of REM sleep Hiromasa Funato 1,5,6 , Makito Sato 1 , Christopher M. Sinton 3 , Laurent Gautron 3 , S.Clay Williams 1 , Joel K. Elmquist 3 , Masaru Kuroda 6 , Arthur I. Skoultchi 4 , Masashi Yanagisawa 1,2,5 1 Department of Molecular Genetics, University of Texas Southwestern Medical Center, Dallas, USA 2 Howard Hughes Medical Institute, USA 3 Department of Internal Medicine, University of Texas Southwestern Medical Center, Dallas, USA 4 Department of Cell Biology, Albert Einstein College of Medicine, New York, USA 5 Center for Behavioral Molecular Genetics, Tsukuba University, Tsukuba, Japan 6 Department of Anatomy, Toho University School of Medicine, Tokyo, Japan
Sleep and wakefulness are primarily regulated by inhibitory interactions between the hypothalamus and brain stem. The expression of the states of rapid eye movement (REM) sleep and non-REM (NREM) sleep are also correlated with the activity of groups of REM-off and REM-on neurons in the dorsal brain stem. However, the contribution of ventral brain stem nuclei to sleep regulation has to date been little characterized. Here we examined sleep and wakefulness in mice deficient in a homeobox transcription factor, Goosecoidlike (Gscl), which is one of the genes deleted in DiGeorge syndrome or 22q11 deletion syndrome. The expression of Gscl is restricted to the interpeduncular nucleus (IP) in the ventral region of the midbrain-hindbrain transition. The IP has tight reciprocal connections with the dorsal region of the brain stem. Although Gscl-/- mice have apparently normal anatomy and connections of the IP, they exhibited a reduced total time spent in REM sleep and fewer REM sleep episodes. In addition, Gscl-/- mice showed reduced theta power during REM sleep and increased arousability during REM sleep. Gscl-/- mice also lacked the expression of DiGeorge syndrome critical region 14 (Dgcr14) in the IP. These results thus indicate that the absence of Gscl and Dgcr14 in the IP affect the normal expression of REM sleep. doi:10.1016/j.neures.2010.07.109
O1-9-3-4 Orexin 2 receptor positively regulates the activity of orexin neurons Sawako Tabuchi , Tomomi Tsunematsu, Makoto Tominaga, Yugo Fukazawa, Akihiro Yamanaka Cell Signaling, NIPS, Aichi Orexin is a neuropeptide which is produced in few number of neurons (orexin neurons) located in the lateral hypothalamic area. Orexin is a natural ligand for two types of G-protein coupled receptors termed OX1R and OX2R. Preproorexin or OX2R null animals showed a fragmentation of sleep/wakefulness and cataplexy-like behavioral arrest. These are similar to symptoms observed in “narcolepsy”, a human sleep disorder. These suggest that orexin and OX2R have an important role in the maintenance of arousal. However, it is not clear that which neurons expressing the OX2R are involved. Electrophysiological analysis of orexin neurons using orexin/EGFP mice, which express EGFP in the orexin neurons, revealed that orexin activates orexin neurons in a concentration dependent manner. Orexin-induced depolarization was observed in the presence of TTX suggests direct activation. Additionally, orexin A and B induced equal level of depolarization suggests an involvement of the OX2R in this response. To determine the receptor subtype, orexin receptor knockout mice were used. Although orexin neurons in the OX1R-/- mice showed equal level of depolarization to orexin/EGFP mice, orexin neurons in the OX2R-/- mice did not show any significant depolarization by applying orexin. These results suggest that orexin activates orexin neurons via the OX2R. Next, we analyzed indirect regulation via glutamatergic neurons. sEPSC frequency to orexin neurons was increased by orexin application in the orexin/EGFP mice and OX1R-/- mice, but not in the OX2R-/mice. On the other hand, immuno-electron microscopic analyses revealed synapse-like structures between orexin neurons, suggesting direct synaptic connection between orexin neurons. In conclusion, orexin activates orexin neurons directly and indirectly via the OX2R. An activation of orexin neurons by other orexin neurons via the OX2R might be involved in the maintenance of arousal. doi:10.1016/j.neures.2010.07.110
Dept Neurobiol & Behav, Grad Sch Biomed Sci, Nagasaki Univ Neural substrates for parental bonding in humans have not been clarified, although several brain areas have been implicated in the parenting in animals. Especially, neural mechanisms underlying human paternal bonding have received less attention. Recently, prefrontal cortex (PFC) has been proved to be a candidate region for maternal bonding in humans by means of fMRI. In the present study, therefore, we examined patterns of PFC activity in mothers and fathers while they are watching their own infants, and compared them to reveal sex difference in the neural basis of parental bonding to their infants.We performed multi-channel near-infrared spectroscopy (NIRS) measurements while mothers and fathers viewed silent video clips of their own infant facial expressions and other age-matched infant’s facial expressions. Mothers and fathers participated in the present study are all biological not fostered. Prior to the NIRS recording, we recorded smiling and neutral facial expressions of participant’s infant. Each video tape was edited into a 30 s-long film clip. In NIRS measurement, video stimuli were presented in a block design. Video stimulus for the baseline block was an infant with a neutral expression and that for the target block was an infant with a smiling expression. Baseline and target lasted for 30 s and were repeated 3 times.We found that the right ventromedial region of the PFC was significantly activated in mothers during viewing the smiling facial expression of their own infant compared with other infant. On the contrary, fathers showed a significant increase in the left ventromedial PFC activity during watching the smiling of their own infants compared with other infants. These results suggest an important role of ventromedial PFC in both maternal and paternal bonding and sexual laterality of neural substrates for parental bonding. doi:10.1016/j.neures.2010.07.111
O1-9-4-2 Experience-dependent choice of fear responses is regulated by the habenula in zebrafish Masakazu Agetsuma 1 , Hidenori Aizawa 1 , Tazu Aoki 1 , Mikako Takahoko 1 , Ryoko Nakayama 1 , Toshiyuki Shiraki 1 , Midori Goto 1 , Koichi Kawakami 2 , Shin-ichi Higashijima 3 , Hitoshi Okamoto 1 1
RIKEN Brain Science Institute, Wako, Japan 2 National Institute of Genetics, Mishima, Japan 3 Okazaki Institute for Integrative Bioscience, Okazaki, Japan
In the last annual meeting, we reported that habenula is an evolutionarily highly conserved diencephalic structure from fish to mammals, and the chronic silencing of zebrafish habenula with genetic methods enhanced freezing responses against the conditioned stimuli after the cued fear conditioning. Here we show more detailed analyses of the mechanisms regulated by the habenula. In zebrafish, the lateral subnuclei of the dorsal habenula (dHbL) are asymmetrically connected with the dorsal and intermediate parts of the interpeduncular nucleus (d/iIPN), which is shown to further project to the periaqueductal gray (PAG). The specific and chronic silencing of this pathway by tetanus toxin rendered animals extraordinarily prone to freeze against conditioned fear stimuli, while, in the same conditioning paradigm, we found that the control fish learnt to show opponent flight behaviors. We also found that there was no difference in the basic locomotor activity and the US sensitivity during the fear conditioning tasks. The modification of fear behaviors by this pathway is experience-dependent. We also used the nitroreductase-based inducible cell death system, and the acute inactivation of this pathway also induced significantly enhanced immobility. These results suggest that habenula might contribute more directly to the information processing for the behavioral choice. Under threatening environments, choice of a suitable response is critical for survival. Our results demonstrate an unprecedented role of the dHbL-d/iIPN-PAG pathway in the choice of fear responses, which might be crucial for the animal survival in the wild. doi:10.1016/j.neures.2010.07.112
Abstracts / Neuroscience Research 68S (2010) e55–e108
responses of the basal forebrain neurons may predict the future cognitive performance.
O1-9-4-1 Sex difference in the neural basis of parental bonding
doi:10.1016/j.neures.2010.07.108
Shota Nishitani , Tsunehiko Takamura, Sho Yamashita, Kazuyuki Shinohara
O1-9-3-3 Loss of Goosecoid-like and Dgcr14 in interpeduncular nucleus alters the expression of REM sleep Hiromasa Funato 1,5,6 , Makito Sato 1 , Christopher M. Sinton 3 , Laurent Gautron 3 , S.Clay Williams 1 , Joel K. Elmquist 3 , Masaru Kuroda 6 , Arthur I. Skoultchi 4 , Masashi Yanagisawa 1,2,5 1 Department of Molecular Genetics, University of Texas Southwestern Medical Center, Dallas, USA 2 Howard Hughes Medical Institute, USA 3 Department of Internal Medicine, University of Texas Southwestern Medical Center, Dallas, USA 4 Department of Cell Biology, Albert Einstein College of Medicine, New York, USA 5 Center for Behavioral Molecular Genetics, Tsukuba University, Tsukuba, Japan 6 Department of Anatomy, Toho University School of Medicine, Tokyo, Japan
Sleep and wakefulness are primarily regulated by inhibitory interactions between the hypothalamus and brain stem. The expression of the states of rapid eye movement (REM) sleep and non-REM (NREM) sleep are also correlated with the activity of groups of REM-off and REM-on neurons in the dorsal brain stem. However, the contribution of ventral brain stem nuclei to sleep regulation has to date been little characterized. Here we examined sleep and wakefulness in mice deficient in a homeobox transcription factor, Goosecoidlike (Gscl), which is one of the genes deleted in DiGeorge syndrome or 22q11 deletion syndrome. The expression of Gscl is restricted to the interpeduncular nucleus (IP) in the ventral region of the midbrain-hindbrain transition. The IP has tight reciprocal connections with the dorsal region of the brain stem. Although Gscl-/- mice have apparently normal anatomy and connections of the IP, they exhibited a reduced total time spent in REM sleep and fewer REM sleep episodes. In addition, Gscl-/- mice showed reduced theta power during REM sleep and increased arousability during REM sleep. Gscl-/- mice also lacked the expression of DiGeorge syndrome critical region 14 (Dgcr14) in the IP. These results thus indicate that the absence of Gscl and Dgcr14 in the IP affect the normal expression of REM sleep. doi:10.1016/j.neures.2010.07.109
O1-9-3-4 Orexin 2 receptor positively regulates the activity of orexin neurons Sawako Tabuchi , Tomomi Tsunematsu, Makoto Tominaga, Yugo Fukazawa, Akihiro Yamanaka Cell Signaling, NIPS, Aichi Orexin is a neuropeptide which is produced in few number of neurons (orexin neurons) located in the lateral hypothalamic area. Orexin is a natural ligand for two types of G-protein coupled receptors termed OX1R and OX2R. Preproorexin or OX2R null animals showed a fragmentation of sleep/wakefulness and cataplexy-like behavioral arrest. These are similar to symptoms observed in “narcolepsy”, a human sleep disorder. These suggest that orexin and OX2R have an important role in the maintenance of arousal. However, it is not clear that which neurons expressing the OX2R are involved. Electrophysiological analysis of orexin neurons using orexin/EGFP mice, which express EGFP in the orexin neurons, revealed that orexin activates orexin neurons in a concentration dependent manner. Orexin-induced depolarization was observed in the presence of TTX suggests direct activation. Additionally, orexin A and B induced equal level of depolarization suggests an involvement of the OX2R in this response. To determine the receptor subtype, orexin receptor knockout mice were used. Although orexin neurons in the OX1R-/- mice showed equal level of depolarization to orexin/EGFP mice, orexin neurons in the OX2R-/- mice did not show any significant depolarization by applying orexin. These results suggest that orexin activates orexin neurons via the OX2R. Next, we analyzed indirect regulation via glutamatergic neurons. sEPSC frequency to orexin neurons was increased by orexin application in the orexin/EGFP mice and OX1R-/- mice, but not in the OX2R-/mice. On the other hand, immuno-electron microscopic analyses revealed synapse-like structures between orexin neurons, suggesting direct synaptic connection between orexin neurons. In conclusion, orexin activates orexin neurons directly and indirectly via the OX2R. An activation of orexin neurons by other orexin neurons via the OX2R might be involved in the maintenance of arousal. doi:10.1016/j.neures.2010.07.110
Dept Neurobiol & Behav, Grad Sch Biomed Sci, Nagasaki Univ Neural substrates for parental bonding in humans have not been clarified, although several brain areas have been implicated in the parenting in animals. Especially, neural mechanisms underlying human paternal bonding have received less attention. Recently, prefrontal cortex (PFC) has been proved to be a candidate region for maternal bonding in humans by means of fMRI. In the present study, therefore, we examined patterns of PFC activity in mothers and fathers while they are watching their own infants, and compared them to reveal sex difference in the neural basis of parental bonding to their infants.We performed multi-channel near-infrared spectroscopy (NIRS) measurements while mothers and fathers viewed silent video clips of their own infant facial expressions and other age-matched infant’s facial expressions. Mothers and fathers participated in the present study are all biological not fostered. Prior to the NIRS recording, we recorded smiling and neutral facial expressions of participant’s infant. Each video tape was edited into a 30 s-long film clip. In NIRS measurement, video stimuli were presented in a block design. Video stimulus for the baseline block was an infant with a neutral expression and that for the target block was an infant with a smiling expression. Baseline and target lasted for 30 s and were repeated 3 times.We found that the right ventromedial region of the PFC was significantly activated in mothers during viewing the smiling facial expression of their own infant compared with other infant. On the contrary, fathers showed a significant increase in the left ventromedial PFC activity during watching the smiling of their own infants compared with other infants. These results suggest an important role of ventromedial PFC in both maternal and paternal bonding and sexual laterality of neural substrates for parental bonding. doi:10.1016/j.neures.2010.07.111
O1-9-4-2 Experience-dependent choice of fear responses is regulated by the habenula in zebrafish Masakazu Agetsuma 1 , Hidenori Aizawa 1 , Tazu Aoki 1 , Mikako Takahoko 1 , Ryoko Nakayama 1 , Toshiyuki Shiraki 1 , Midori Goto 1 , Koichi Kawakami 2 , Shin-ichi Higashijima 3 , Hitoshi Okamoto 1 1
RIKEN Brain Science Institute, Wako, Japan 2 National Institute of Genetics, Mishima, Japan 3 Okazaki Institute for Integrative Bioscience, Okazaki, Japan
In the last annual meeting, we reported that habenula is an evolutionarily highly conserved diencephalic structure from fish to mammals, and the chronic silencing of zebrafish habenula with genetic methods enhanced freezing responses against the conditioned stimuli after the cued fear conditioning. Here we show more detailed analyses of the mechanisms regulated by the habenula. In zebrafish, the lateral subnuclei of the dorsal habenula (dHbL) are asymmetrically connected with the dorsal and intermediate parts of the interpeduncular nucleus (d/iIPN), which is shown to further project to the periaqueductal gray (PAG). The specific and chronic silencing of this pathway by tetanus toxin rendered animals extraordinarily prone to freeze against conditioned fear stimuli, while, in the same conditioning paradigm, we found that the control fish learnt to show opponent flight behaviors. We also found that there was no difference in the basic locomotor activity and the US sensitivity during the fear conditioning tasks. The modification of fear behaviors by this pathway is experience-dependent. We also used the nitroreductase-based inducible cell death system, and the acute inactivation of this pathway also induced significantly enhanced immobility. These results suggest that habenula might contribute more directly to the information processing for the behavioral choice. Under threatening environments, choice of a suitable response is critical for survival. Our results demonstrate an unprecedented role of the dHbL-d/iIPN-PAG pathway in the choice of fear responses, which might be crucial for the animal survival in the wild. doi:10.1016/j.neures.2010.07.112