The Experts below are selected from a list of 294 Experts worldwide ranked by ideXlab platform
Tsuyoshi Miyakawa - One of the best experts on this subject based on the ideXlab platform.
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comprehensive behavioral phenotyping of a new semaphorin 3 f mutant mouse
Molecular Brain, 2016Co-Authors: Atsu Aiba, Hirotaka Shoji, Tsuyoshi Miyakawa, Ikuo Matsuda, Nobuyuki YamasakiAbstract:Semaphorin 3 F (Sema3F) is a secreted type of the Semaphorin family of axon guidance molecules. Sema3F and its receptor neuropilin-2 (Npn-2) are expressed in a mutually exclusive manner in the embryonic mouse brain regions including olfactory bulb, hippocampus, and cerebral cortex. Sema3F is thought to have physiological functions in the formation of neuronal circuitry and its refinement. However, functional roles of Sema3F in the brain remain to be clarified. Here, we examined behavioral effects of Sema3F deficiency through a comprehensive behavioral Test battery in Sema3F knockout (KO) male mice to understand the possible functions of Sema3F in the brain. Male Sema3F KO and wild-type (WT) control mice were subjected to a battery of behavioral Tests, including neurological screen, rotarod, hot plate, prepulse inhibition, light/dark transition, open field, elevated plus maze, social interaction, Porsolt forced swim, tail suspension, Barnes maze, and Fear Conditioning Tests. In the open field Test, Sema3F KO mice traveled shorter distance and spent less time in the center of the field than WT controls during the early Testing period. In the light/dark transition Test, Sema3F KO mice also exhibited decreased distance traveled, fewer number of transitions, and longer latency to enter the light chamber compared with WT mice. In addition, Sema3F KO mice traveled shorter distance than WT mice in the elevated plus maze Test, although there were no differences between genotypes in open arm entries and time spent in open arms. Similarly, Sema3F KO mice showed decreased distance traveled in the social interaction Test. Sema3F KO mice displayed reduced immobility in the Porsolt forced swim Test whereas there was no difference in immobility between genotypes in the tail suspension Test. In the Fear Conditioning Test, Sema3F KO mice exhibited increased freezing behavior when exposed to a Conditioning context and an altered context in absence of a conditioned stimulus. In the Tests for assessing motor function, pain sensitivity, startle response to an acoustic stimulus, sensorimotor gating, or spatial reference memory, there were no significant behavioral differences between Sema3F KO and WT mice. These results suggest that Sema3F deficiency induces decreased locomotor activity and possibly abnormal anxiety-related behaviors and also enhances contextual memory and generalized Fear in mice. Thus, our findings suggest that Sema3F plays important roles in the development of neuronal circuitry underlying the regulation of some aspects of anxiety and Fear responses.
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Contextual and cued Fear Conditioning Test using a video analyzing system in mice.
Journal of visualized experiments : JoVE, 2014Co-Authors: Hirotaka Shoji, Keizo Takao, Satoko Hattori, Tsuyoshi MiyakawaAbstract:The contextual and cued Fear Conditioning Test is one of the behavioral Tests that assesses the ability of mice to learn and remember an association between environmental cues and aversive experiences. In this Test, mice are placed into a Conditioning chamber and are given parings of a conditioned stimulus (an auditory cue) and an aversive unconditioned stimulus (an electric footshock). After a delay time, the mice are exposed to the same Conditioning chamber and a differently shaped chamber with presentation of the auditory cue. Freezing behavior during the Test is measured as an index of Fear memory. To analyze the behavior automatically, we have developed a video analyzing system using the ImageFZ application software program, which is available as a free download at http://www.mouse-phenotype.org/. Here, to show the details of our protocol, we demonstrate our procedure for the contextual and cued Fear Conditioning Test in C57BL/6J mice using the ImageFZ system. In addition, we validated our protocol and the video analyzing system performance by comparing freezing time measured by the ImageFZ system or a photobeam-based computer measurement system with that scored by a human observer. As shown in our representative results, the data obtained by ImageFZ were similar to those analyzed by a human observer, indicating that the behavioral analysis using the ImageFZ system is highly reliable. The present movie article provides detailed information regarding the Test procedures and will promote understanding of the experimental situation.
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orexin receptor 1 in the locus coeruleus plays an important role in cue dependent Fear memory consolidation
The Journal of Neuroscience, 2013Co-Authors: Shingo Soya, Hirotaka Shoji, Mari Hondo, Emi Hasegawa, Michihiro Mieda, Masashi Yanagisawa, Tsuyoshi Miyakawa, Takeshi SakuraiAbstract:The noradrenergic (NA) projections arising from the locus ceruleus (LC) to the amygdala and bed nucleus of the stria terminalis have been implicated in the formation of emotional memory. Since NA neurons in the LC (LC-NA neurons) abundantly express orexin receptor-1 (OX1R) and receive prominent innervation by orexin-producing neurons, we hypothesized that an OX1R-mediated pathway is involved in the physiological Fear learning process via regulation of LC-NA neurons. To evaluate this hypothesis, we examined the phenotype of Ox1r −/− mice in the classic cued and contextual Fear-Conditioning Test. We found that Ox1r −/− mice showed impaired freezing responses in both cued and contextual Fear-Conditioning paradigms. In contrast, Ox2r −/− mice showed normal freezing behavior in the cued Fear-Conditioning Test, while they exhibited shorter freezing time in the contextual Fear-Conditioning Test. Double immunolabeling of Fos and tyrosine hydroxylase showed that double-positive LC-NA neurons after Test sessions of both cued and contextual stimuli were significantly fewer in Ox1r −/− mice. AAV-mediated expression of OX1R in LC-NA neurons in Ox1r −/− mice restored the freezing behavior to the auditory cue to a comparable level to that in wild-type mice in the Test session. Decreased freezing time during the contextual Fear Test was not affected by restoring OX1R expression in LC-NA neurons. These observations support the hypothesis that the orexin system modulates the formation and expression of Fear memory via OX1R in multiple pathways. Especially, OX1R in LC-NA neurons plays an important role in cue-dependent Fear memory formation and/or retrieval.
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P301S Mutant Human Tau Transgenic Mice Manifest Early Symptoms of Human Tauopathies with Dementia and Altered Sensorimotor Gating
PloS one, 2011Co-Authors: Hiroki Takeuchi, Tsuyoshi Miyakawa, Keizo Takao, Michiyo Iba, Haruhisa Inoue, Makoto Higuchi, Kayoko Tsukita, Yoshiko Karatsu, Yumiko Iwamoto, Tetsuya SuharaAbstract:Tauopathies are neurodegenerative disorders characterized by the accumulation of abnormal tau protein leading to cognitive and/or motor dysfunction. To understand the relationship between tau pathology and behavioral impairments, we comprehensively assessed behavioral abnormalities in a mouse tauopathy model expressing the human P301S mutant tau protein in the early stage of disease to detect its initial neurological manifestations. Behavioral abnormalities, shown by open field Test, elevated plus-maze Test, hot plate Test, Y-maze Test, Barnes maze Test, Morris water maze Test, and/or contextual Fear Conditioning Test, recapitulated the neurological deficits of human tauopathies with dementia. Furthermore, we discovered that prepulse inhibition (PPI), a marker of sensorimotor gating, was enhanced in these animals concomitantly with initial neuropathological changes in associated brain regions. This finding provides evidence that our tauopathy mouse model displays neurofunctional abnormalities in prodromal stages of disease, since enhancement of PPI is characteristic of amnestic mild cognitive impairment, a transitional stage between normal aging and dementia such as Alzheimer's disease (AD), in contrast with attenuated PPI in AD patients. Therefore, assessment of sensorimotor gating could be used to detect the earliest manifestations of tauopathies exemplified by prodromal AD, in which abnormal tau protein may play critical roles in the onset of neuronal dysfunctions.
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synaptic e3 ligase scrapper in contextual Fear Conditioning extensive behavioral phenotyping of scrapper heterozygote and overexpressing mutant mice
PLOS ONE, 2011Co-Authors: Tsuyoshi Miyakawa, Keizo Takao, Ikuko Yao, Seiji Ito, Mitsutoshi SetouAbstract:SCRAPPER, an F-box protein coded by FBXL20, is a subunit of SCF type E3 ubiquitin ligase. SCRAPPER localizes synapses and directly binds to Rab3-interacting molecule 1 (RIM1), an essential factor for synaptic vesicle release, thus it regulates neural transmission via RIM1 degradation. A defect in SCRAPPER leads to neurotransmission abnormalities, which could subsequently result in neurodegenerative phenotypes. Because it is likely that the alteration of neural transmission in Scrapper mutant mice affect their systemic condition, we have analyzed the behavioral phenotypes of mice with decreased or increased the amount of SCRAPPER. We carried out a series of behavioral Test batteries for Scrapper mutant mice. Scrapper transgenic mice overexpressing SCRAPPER in the hippocampus did not show any significant difference in every Test argued in this manuscript by comparison with wild-type mice. On the other hand, heterozygotes of Scrapper knockout [SCR (+/−)] mice showed significant difference in the contextual but not cued Fear Conditioning Test. In addition, SCR (+/−) mice altered in some Tests reflecting anxiety, which implies the loss of functions of SCRAPPER in the hippocampus. The behavioral phenotypes of Scrapper mutant mice suggest that molecular degradation conferred by SCRAPPER play important roles in hippocampal-dependent Fear memory formation.
Ichiro Kusumi - One of the best experts on this subject based on the ideXlab platform.
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combined treatment with subchronic lithium and acute intracerebral mirtazapine microinjection into the median raphe nucleus exerted an anxiolytic like effect synergistically
European Journal of Pharmacology, 2016Co-Authors: Yan An, Yuji Kitaichi, Shin Nakagawa, Takeshi Inoue, Chong Chen, Ce Wang, Ichiro KusumiAbstract:Abstract Although preclinical and clinical studies have established the efficacy of lithium augmentation of antidepressant drugs, the mechanism of action of lithium augmentation is not fully understood. Our previous study reported that subchronic lithium treatment enhanced the anxiolytic-like effect of systemic mirtazapine. In the present study, we examined the effect of subchronic lithium in combination with acute local intracerebral injection of mirtazapine on Fear-related behaviors in a contextual Fear Conditioning Test in rats to clarify the target brain region of lithium augmentation of mirtazapine. After Conditioning by footshock, diet (food pellets) containing Li 2 CO 3 at a concentration of 0.2% was administered for 7 days. Ten min before Testing and 7 days after Conditioning, mirtazapine (3 μg/site) in a volume of 0.5 µl was acutely injected into the median raphe nucleus (MRN), hippocampus or amygdala. The combination of subchronic lithium and acute mirtazapine microinjection into the MRN but not the hippocampus or the amygdala reduced Fear expression synergistically. These results suggest that intra-MRN mirtazapine treatment with subchronic lithium exerts the anxiolytic-like effect through the facilitation of the MRN-5HT pathway.
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Subchronic lithium treatment increases the anxiolytic-like effect of mirtazapine on the expression of contextual conditioned Fear
European journal of pharmacology, 2014Co-Authors: Takeshi Inoue, Yuji Kitaichi, Shin Nakagawa, Chong Chen, Ce Wang, Ning Song, Ichiro KusumiAbstract:Lithium not only has a mood-stabilizing effect but also the augmentation effect of an antidepressant, the mechanism of which remains unclear. Although lithium may augment the effect of mirtazapine, this augmentation has not been confirmed. Using a contextual Fear Conditioning Test in rats, an animal model of anxiety or Fear, we examined the effect of subchronic lithium carbonate (in diet) in combination with systemic mirtazapine on the expression of contextual conditioned Fear. Mirtazapine (10mg/kg) reduced freezing one day after Fear Conditioning dose-dependently, whereas the anxiolytic-like effect of mirtazapine (10mg/kg) diminished seven days after Fear Conditioning. When the interval between Fear Conditioning and Testing was seven days, only the combination of subchronic 0.2% Li2CO3 but not 0.05% Li2CO3 with acute mirtazapine (10mg/kg) reduced freezing significantly. These results indicate that subchronic 0.2% Li2CO3 treatment enhanced the anxiolytic-like effect of systemic mirtazapine. This augmentation therapy might be useful for the treatment of anxiety disorders.
Eero Vasar - One of the best experts on this subject based on the ideXlab platform.
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Targeted invalidation of CCK2 receptor gene induces anxiolytic-like action in light–dark exploration, but not in Fear Conditioning Test
Psychopharmacology, 2005Co-Authors: Sirli Raud, Jürgen Innos, Urho Abramov, Ain Reimets, Sulev Kõks, Andres Soosaar, Toshimitsu Matsui, Eero VasarAbstract:Rationale Evidence suggests that γ-aminobutyric acid (GABA) and cholecystokinin (CCK) have opposite roles in the regulation of anxiety.
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targeted invalidation of cck2 receptor gene induces anxiolytic like action in light dark exploration but not in Fear Conditioning Test
Psychopharmacology, 2005Co-Authors: Sirli Raud, Jürgen Innos, Urho Abramov, Ain Reimets, Sulev Kõks, Andres Soosaar, Toshimitsu Matsui, Eero VasarAbstract:Rationale Evidence suggests that γ-aminobutyric acid (GABA) and cholecystokinin (CCK) have opposite roles in the regulation of anxiety.
Mitsutoshi Setou - One of the best experts on this subject based on the ideXlab platform.
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synaptic e3 ligase scrapper in contextual Fear Conditioning extensive behavioral phenotyping of scrapper heterozygote and overexpressing mutant mice
PLOS ONE, 2011Co-Authors: Tsuyoshi Miyakawa, Keizo Takao, Ikuko Yao, Seiji Ito, Mitsutoshi SetouAbstract:SCRAPPER, an F-box protein coded by FBXL20, is a subunit of SCF type E3 ubiquitin ligase. SCRAPPER localizes synapses and directly binds to Rab3-interacting molecule 1 (RIM1), an essential factor for synaptic vesicle release, thus it regulates neural transmission via RIM1 degradation. A defect in SCRAPPER leads to neurotransmission abnormalities, which could subsequently result in neurodegenerative phenotypes. Because it is likely that the alteration of neural transmission in Scrapper mutant mice affect their systemic condition, we have analyzed the behavioral phenotypes of mice with decreased or increased the amount of SCRAPPER. We carried out a series of behavioral Test batteries for Scrapper mutant mice. Scrapper transgenic mice overexpressing SCRAPPER in the hippocampus did not show any significant difference in every Test argued in this manuscript by comparison with wild-type mice. On the other hand, heterozygotes of Scrapper knockout [SCR (+/−)] mice showed significant difference in the contextual but not cued Fear Conditioning Test. In addition, SCR (+/−) mice altered in some Tests reflecting anxiety, which implies the loss of functions of SCRAPPER in the hippocampus. The behavioral phenotypes of Scrapper mutant mice suggest that molecular degradation conferred by SCRAPPER play important roles in hippocampal-dependent Fear memory formation.
Mitsuhiro Yoshioka - One of the best experts on this subject based on the ideXlab platform.
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The Serotonergic Projection from the Median Raphe Nucleus to the Ventral Hippocampus is Involved in the Retrieval of Fear Memory Through the Corticotropin-Releasing Factor Type 2 Receptor
Neuropsychopharmacology, 2010Co-Authors: Yu Ohmura, Taku Yamaguchi, Takeshi Izumi, Iku Tsutsui-kimura, Takayuki Yoshida, Mitsuhiro YoshiokaAbstract:Several different studies have separately established that serotonin, corticotropin-releasing factor (CRF) receptors, and the hippocampus are involved in Fear memory retrieval. The main aim of this study is to connect these separate studies. To assess the levels of anxiety/Fear, we used the contextual Fear-Conditioning Test and the elevated plus maze Test as memory-dependent and memory-independent tasks, respectively. We injected CRF receptor antagonists or vehicle into the median raphe nucleus (MRN) 10 min before behavioral Tests. As a result, 1000 ng of astressin 2B (CRF_2 receptor antagonist), but not 250 ng of antalarmin (CRF_1 receptor antagonist), significantly suppressed the expression rate of freezing behavior in the contextual Fear-Conditioning Test. However, in the elevated plus maze Test, there was no difference between astressin 2B-injected rats and saline-injected rats in the time spent in open arms. Neither the amount of exploratory behavior nor the moving distance in the EPM of astressin 2B-injected rats differed from that of vehicle-injected rats. Moreover, when we assessed the extracellular serotonin release in the ventral hippocampus in freely moving rats through in vivo microdialysis, it was shown that the blockade of the CRF_2 receptor in the MRN suppressed serotonin release in the ventral hippocampus during Fear memory retrieval. These results indicated that endogenous CRF and/or related ligands that were released in the MRN could activate the CRF_2 receptor and stimulate serotonin release in the ventral hippocampus, thereby inducing Fear memory retrieval.
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corticotropin releasing factor in the median raphe nucleus is involved in the retrieval of Fear memory in rats
European Journal of Pharmacology, 2008Co-Authors: Yu Ohmura, Taku Yamaguchi, Takeshi Izumi, Machiko Matsumoto, Mitsuhiro YoshiokaAbstract:In the present study, we examined the role of corticotropin releasing factor (CRF) in the median raphe nucleus (MRN) on Fear-related behaviors in rats. We employed the contextual Fear Conditioning Test and the elevated plus maze Test as memory-dependent and -independent tasks, respectively. Human/rat CRF (10 ng) in 0.5 μl saline was injected into the MRN. Administration of CRF significantly increased memory dependent, but not independent, Fear expression. These results suggest that CRF release in the MRN is involved in the retrieval of Fear memory.
