e ポスター

e ポスター 12. 認知、行動、情動 e Poster 12. Cognitiion, Behavior, Emotion

2020/9/12　13:40～14:40　オンデマンドB-1 P3-07 オプトジェネティクスを用いた局所脳血流の操作技術 Optogenetics manipulation of local cerebral blood flow in the deep brain in freely moving mice 阿部欣史¹、田中謙二¹ 1. 慶應義塾大学医学部 Yoshifumi Abe¹, Kenji F Tanaka¹ 1. Keio University School of Medicine Artificial manipulation tool of local cerebral blood flow (CBF) is required to understand how the cerebral blood flow (CBF) controls the brain function. Here, we generated vascular optogenetics resources in which smooth muscle cells and endothelial cells expressed optical actuators in the brain. An illumination upon channelrhodopsin-2 (ChR2)-expressing mice induced a local CBF reduction. Photoactivated adenylyl cyclase (PAC) is an optical probe to increase intracellular cyclic adenosine monophosphate (cAMP) and an illumination upon PAC-expressing mice induced a local CBF increase. We targeted the ventral striatum, determined the temporal kinetics of CBF change, and optimized the illumination intensity to confine the effect in the ventral striatum. We exemplified the vascular optogenetic manipulation in freely and adaptively behaving mice. Vascular optogenetic animal resources will accelerate the research linking among vasculature, circuit, and behavior in health and disease.		2020/9/12　13:40～14:40　オンデマンドB-1 P3-08 におい刺激による前嗅核の電気生理 Coding of odors in the anterior olfactory nucleus 辻隆宏^1,2,3、辻　知陽³、ロジクマヤ⁴、ルードビックマイク^4,5、レングゲリス⁴ 1. 福井大学医学部眼科学、2. 福井大学ライフサイエンスイノベーションセンター、3. 金沢大学子どものこころ発達研究センター、4. エジンバラ大学、5. プレトリア大学 Takahiro Tsuji^1,2,3, Chiharu Tsuji³, Maja Lozic⁴, Mike Ludwig^4,5, Gareth Leng⁴ 1. Dept. of ophthalmology, Faculty of medicine, Fukui Univ., 2. Life science innovation center, Fukui Univ., 3. Kanazawa Univ., Research center for child mental development, 4. Centre for Discovery Brain Sciences, University of Edinburgh, 5. Department of Immunology, Centre for Neuroendocrinology, University of Pretoria Odorant molecules stimulate olfactory receptor neurons, and axons of these neurons project into the main olfactory bulb where they synapse onto mitral and tufted cells. These project to the primary olfactory cortex including the anterior olfactory nucleus (AON), the piriform cortex, amygdala, and the entorhinal cortex. The properties of mitral cells have been investigated extensively, but how odor information is processed in subsequent brain regions is less well known. In the present study, we recorded the electrical activity of AON neurons in anesthetized rats. Most AON cells fired in bursts of 2–10 spikes separated by very short intervals (<20 ms), in a period linked to the respiratory rhythm. Simultaneous recordings from adjacent neurons revealed that the rhythms of adjacent cells, while locked to the same underlying rhythm, showed marked differences in phase. We studied the responses of AON cells to brief high frequency stimulation of the lateral olfactory tract, mimicking brief activation of mitral cells by odor. In different cells, such stimuli evoked transient or sustained bursts during stimulation or, more commonly, post-stimulation bursts after inhibition during stimulation. This suggests that, in AON cells, phase shifts occur as a result of post-inhibitory rebound firing, following inhibition by mitral cell input, and we discuss how this supports processing of odor information in the olfactory pathway. Cells were tested for their responsiveness to a social odor (the bedding of a strange male) among other simple and complex odors tested. In total, 11 cells responded strongly and repeatedly to bedding odor, and these responses were diverse, including excitation (transient or sustained), inhibition, and activation after odor presentation, indicating that AON neurons respond not only to the type of complex odor but also to temporal features of odor application.

2020/9/12　13:40～14:40　オンデマンドB-1 P3-09 バルプロ酸暴露マウスの母子分離により誘導される超音波発声に対するオキシトシンの改善効果 Oxytocin ameliorates maternal separation-induced ultrasonic vocalization calls in mouse pups prenatally exposed to valproic acid 辻知陽¹、藤咲友朗¹、辻隆宏^1,2 1. 金沢大学子どものこころの発達研究センター、2. 福井大学医学部眼科 Tsuji Chiharu¹, Tomoaki Fujisaku¹, Takahiro Tsuji^1,2 1. Research Center for Child Mental Development, Kanazawa University, 2. Deapartment of Opthalomology, Faculty of Medical Sciences, Life Innovation center, University of Fukui Introdauction Autism spectrum disorder (ASD) is a neurodevelopmental disorder estimated by the World Health Organization to occur in one of 160 children worldwide. No pharmaceutical treatments are available to improve the deficits in social communication that are common symptoms of ASD. Recent clinical trials have focused on the nasal application of oxytocin, a neuronal peptide known to regulate a variety of social behaviors. However, the effect of oxytocin on this deficit is inconclusive. In contrast, evidence from ASD animal model studies indicates that when animals are treated with oxytocin during early development, improvements in social deficits are observed in adulthood. Thus, it is necessary to examine the effect of therapeutic target medication prescribed in early development. Mice prenatally exposed to valproic acid (VPA) are widely used as an animal model of ASD. However, many behavioral studies have been conducted during adulthood rather than early development. Purpose To establish a screening system to identify therapeutic drugs that are effective when delivered during the early postnatal period using VPA-exposed mice pups. Methods: The maternal separation induced ultrasonic vocalization (USV) of VPA-exposed mice pups were analysed. Result: USV rates were comparable to those of the controls until the first week of their life but declined more on postnatal day 11 in VPA pups. The gene expression of oxytocin system in the hypothalamus was altered in the VPA pups. Acute administration of oxytocin on postnatal day 11 increased the call rate of VPA pups. Conclusion: There was a deficiency in the oxytocinergic signaling in the VPA pups and oxytocin administration can ameliorates the decreased rate of USV. Furthermore, we showed the existence of time periods that are effective to screen the therapeutic drugs.		2020/9/12　13:40～14:40　オンデマンドB-1 P3-10 新生仔ラット低酸素虚血性白質傷害後の豊かな環境飼育による大脳皮質II/III層樹状突起の形態変化とオリゴデンドロサイトの分化促進 Enriched environment after hypoxic-ischemia normalizes dendrite morphology of the cortex layer II/III accompanied with oligodendrocyte differentiation in rat of neonatal white matter injury 飛田秀樹¹、服部篤紀¹、清水健史¹、田尻直輝¹ 1. 名古屋市立大学医学研究科 Hideki Hida¹, Atsunori Hattori¹, Takeshi Shimizu¹, Naoki Tajiri¹ 1. Nagoya City Univ Grad Sch Med Sci Hypoxia-ischemia (H-I) in preterm infants occasionally results in neonatal white matter injury (WMI) associated with neurodevelopmental disabilities. Although we previously reported the improvement of disturbed motor function in neonatal WMI by enriched environment (EE) that contains increased motor activity, social interaction and exploration, the cell dynamics in EE effect on neonatal WMI model is still unclear. To investigate whether EE during the period of development can change microenvironment of a neonatal WMI model affecting on cell morphology and cell differentiation, rat neonatal WMI model made by H-I at P3 was grown in either condition of EE or standard environment (SE) from P25 to P70, followed by morphological and immunohistochemical assessments. In the WMI model under SE, significantly complex dendrites with many branching were shown in H-I side of the cortex compared in the contralateral side. However, similar extension pattern was observed by Sholl analysis in both side of the cortex in the neonatal WMI model under EE, which is comparable to the pattern in Sham groups. Interestingly, the complexity of the dendrites in the cortex layer II/III in WMI-EE group was normalized to those in sham group. In addition to morphological changes in the layer II/III, oligodendrocyte (0L) differentiation was induced by EE: significant increase of mature OL was shown on the upper area of ipsilateral motor cortex, and stronger MBP intensity was also detected in WMI-EE group These data suggested that EE during the period of development has significant effects on disturbed microenvironment in a rat neonatal WMI model, affecting on dendrite morphology of the layer II/III of the sensorimotor cortex and OL differentiation.

2020/9/12　13:40～14:40　オンデマンドB-1 *P3-11【演題取消】**		2020/9/12　13:40～14:40　オンデマンドB-1 P3-12* Shank3欠損マウスが示す行動異常 Behavioral abnormalities in Shank3-deficient mice 宇和野水優¹、清水仁美¹、金光明音¹、崎村建司²、内野茂夫¹ 1. 帝京大学大学院理工学研究科、2. 新潟大学脳研究所 Miyu Uwano¹, Hitomi Shimizu¹, Akane Kanamitsu¹, Kenji Sakimura², Shigeo Uchino¹ 1. Graduate School of Science and Engineering, Teikyo University, 2. Brain Research Institute, Niigata University The SHANK3 gene has been identified as a responsible gene for Phelan-McDermid syndrome, which is an autistic disorder with severe language impairment and mental retardation. The SHANK3 gene encodes a scaffolding protein that interacts with various synaptic molecules, including PSD95 and neuroligin. Recent genetic studies with autism spectrum disorder (ASD) patients strongly supported relation between molecular defects of SHANK3 and ASD. Different Shank3-deficient mice line have been produced and have contributed to investigation of the synaptic function of SHANK3 and of the neuropathology of ASD. We also produced novel Shank3-deficient mice and carried out behavior analysis. The open-field test is a behavioral test for investigating the exploratory behavior, spontaneous locomotor activity, and anxiety behavior of a mouse in a new environment. In this study, the Shank3-deficient mice had a similar average speed to wild-type mice, but their total distance was significantly shorter and their total resting time was significantly longer. This result confirmed that the Shank3-deficient mice performed frequent and long-time grooming from the video analysis. Moreover, the number of entries into the internal region for determining anxiety was smaller in the Shank3-deficient mice, suggesting that anxiety may be enhanced. On the other hand, as a test for judging sociality, an interaction with 11-day-old ICR pups was performed. As a result, the Shank3-deficient mice showed excessive vigilance to avoid the pups, and persistently chased the pups with excessive sniffing and attack. We are currently investigating molecules that differ in expression between the Shank3-deficient mice and wild-type mice in order to elucidate the mechanism that causes abnormal behavior.

2020/9/12　13:40～14:40　オンデマンドB-1 P3-13* 胎児期グリホサート曝露ラットにおける行動異常と腸内細菌叢変化 Behavioral alteration and microbiome transition of the prenatal glyphosate-treated rat 大室拓平¹、宮本佳菜¹、Thomas Tiong Kwong Soon¹、諫田泰成²、吉田祥子¹ 1. 豊橋技術科学大学、2. 国立医薬品食品衛生研究所 Takuhei Omuro¹, Kana Miyamoto¹, Kwong Soon Thomas Tiong¹, Yasunari Kanda², Sachiko Yoshida¹ 1. TUT, 2. NIHS Glyphosate (GLY), the main compound of a broadly applied herbicide, is the negative substance on the Organization for Economic Cooperation and Development (OECD) Test Guidelines; however, the neurodevelopmental safeties of GLY are unknown. The primary herbicidal function of GLY is to inhibit a key plant enzyme, 5-enolpyruvylshikimate-3-phosphate synthase (EPSPS), which participates in the biosynthesis of aromatic amino acids via the shikimate pathway in bacteria, fungi, and plants, so that GLY may have the potential to modify the animal gut microbiota. Previously we have shown that acute exposure of 250 mg/kg- GLY to pregnant rats at G15 lead to Purkinje cell death and behavioral disorder in developing cerebellum of the offspring. In this study, we investigated cerebellar development, behavioral alteration, and microbiome transition of the GLY-treated rat. 4-weeks old GLY-treated rats showed the decrease of Purkinje cells and the increase of microglia on the Purkinje layer, and in their gut microbiome, the abundance butyric acid-producing bacteria and lactic acid bacteria were decreased. 6-week old GLY-treated male rats showed an increase in grooming time related to anxiety and a decrease in contact time with the object. To investigate the recovery potential of butyric acid, we administrated butyric acid p.o. to GLY-treated pups for a week after birth. Three weeks after birth, the number of Purkinje cells in GLY-treated pups recovered with butyric acid administration, while the number of microglia was similar to GLY-treated pups without butyric acid. We suggest that a part of GLY-neurotoxicity would induce microbiome transition, and butyric acid administration may have a therapeutic effect on the GLY toxicity.		2020/9/12　13:40～14:40　オンデマンドB-1 P3-14* CPF神経毒性のAChE誘導性検討 Mechanism of developmental neurotoxicity of chlorpyriphos due to AChE inhibition 松房利恵¹、諫田泰成²、吉田祥子¹ 1. 豊橋技術科学大学、2. 国立医薬品食品衛生研究所 Rie Matsufusa¹, Yasunari Kanda², Sachiko Yoshida¹ 1. TUT, 2. National Institute of Health Sciences Multiple environmental factors, including medical drugs, have been associated with neuronal and mental disorders. Recently, some reports show some structural abnormalities of the cerebellum are observed in autistic patients, especially reductions in Purkinje cell (PC) size and number. We have reported valproate (VPA) -treated autism model rat showed enhanced Purkinje cell development and excess folding in cerebellar lobules. In addition, VPA-treated adult rats behaved as if they had ASD and ADHD. In this study, we report the mechanism of neurodevelopmental toxicity of Chlorpyrifos (CPF). CPF is one of the well-known autism inducers, and an organophosphorus insecticide used to control pests in various food and feed crops. Despite that exposure of pregnant women to CPF has the incidence of autism in children, the mechanisms of its developmental neurotoxicity are not fully understood. Prenatal CPF-exposed rat pups were born small in size, and some pups were extremely small. Cerebellar lobule development looked normal; however, irregular distribution of the PC somas was observed, and the length of PC dendrites was shorter than the control one. We suggest some mitochondrial disfunction would induce this abnormality. CPF is one of the Choline esterase inhibitors, and CPF-exposed rat pups showed a decrease in swimming ability and elongation of the time required for turning over. We investigated the effect of Donepezil, another AChE inhibitor, and observed Donepezil-treated pups at the same doze of CPF died shortly after birth. We suggest that AChE inhibitor would induce mitochondrial dysfunction during the neurodevelopmental period.