Oral Sessions

Oral Sessions 神経ネットワーク

3O1-1 FABP3 deficiency causes impaired fear extinction as PTSD-like behaviors. Yasushi Yabuki¹，Ibuki Takahata¹，Yuji Owada²，Kohji Fukunaga¹ ¹Dept Pharmacol. Grad Sch Pharm Sci, Tohoku Univ，²Dept Organ Anatomy. Grad Sch Med, Tohoku Univ Fatty acid binding protein 3 (FABP3, H-FABP) binds to the intracellular loop of dopamine D2L receptor, and FABP3 null mice show dysfunction of dopamine-regulated motor coordination. Here we indicate that FABP3 null mice exhibit impaired fear extinction, and thus show post-traumatic stress disorder (PTSD)-like behaviors. Animals were subject to fear conditioning once a day with consecutive 4 days and measured the fear acquisition and extinction for 35 days. FABP3 null mice show normal acquisition of contextual fear memory like wild type mice. One month after exposure to contextual stimulation, wild type mice showed reduction of the elapsed time until entering the chamber given footshock, indicating normal extinction. However, the elapsed time remained elevated in FABP3 null mice. Related to mechanisms underlying impaired fear extinction, calcium/calmodulin-dependent protein kinase II (CaMKII) autophosphorylation levels were markedly reduced in the anterior cingulate cortex (ACC) in FABP3 null mice. Inversely, CaMKII autophosphorylation increased in the basolateral amygdala (BLA). Likewise, the number of c-Fos positive cells in BLA significantly were elevated after exposure to contextual fear conditions but not in the central nucleus of the amygdala (CeA). Chronic administration of ramelteon (1.0 mg/kg, p.o.) attenuated abnormal autophosphorylated CaMKII and c-Fos expression levels, thereby improving PTSD-like behaviors in FABP3 null mice. In addition, luzindole (2.5 mg/kg, i.p.) significantly blocked the effect of ramelteon in FABP3 null mice. Taken together, FABP3 null mice are novel model of PTSD and ramelteon is possible therapeutics for PTSD-like behaviors (Yabuki Y and Fukunaga K et al., 2017. Mol Neurobiol. In press).		3O1-2 Neuropsin participate in social memory Hitomi Nakazawa¹，Yuka Suzuki²，Yasuyuki Ishikawa²，Sadao Shiosaka³，Shigetaka Yoshida¹ ¹Department of Functional Anatomy and Neuroscience, Asahikawa Medical University，² Department of Systems Life Engineering, Maebashi Institute of Technology，³Faculty of Health Science, Osaka Yukioka College of Health Science For social mammals from rodent to human, recognition and acquisition familiar conspecifics (social memory) is crucial to living in and stabilize the colony. Although underlying mechanism of the social memory is not yet understood well, accumulating evidence has suggested that neural plasticity might be associated with the social memory. Evidence has shown that an extracellular proteolysis plays significant role in modification of plasticity in neural network during memory acquisition and cognition. Neuropsin (NP) is suggested to be involved in E–LTP, regulation of gamma oscillation and spacial working memory. NP is also suggested to modify signal proteins in the hippocampus in memory acquisition and cognitive processes. To investigate the function of NP in memory acquisition and social behavior, we first investigated the endogenous NP activity and presumed relation of synaptic signaling in the hippocampus using a modified resident–intruder paradigm. Then, we used NP–knockout mice in three–chamber test to investigate the role of NP in sociability and social discrimination. We found that intrusion of a novel mouse induced the expression of Arc in principal hippocampal neurons. Furthermore, proteinase activation of NP and phosphorylation of ErbB4, a putative downstream cascade of NP, were detected. NP–knockout mice exhibited normal social approach, however, these mice stayed less time in the area of a novel mice, suggesting a reduction in novel conspecific cognition. These data suggest that NP participates in social memory by modifying signal proteins and regulates the precise social discrimination.

3O1-3 Investigation of cytological architectures in the brains of newly established mouse models with cognitive impairments Ken-ichiro Kubo¹，Kimiko Deguchi^1,2，Kazuhiro Ishii¹，Ken Inoue²，Kazunori Nakajima¹ ¹Dept Anat, Keio Univ Sch of Med，²Dept MR & BD Res, NIN, NCNP Abnormal cytological architecture has been pointed out as one of the microscopic pathological findings in the brains of patients with neuropsychiatric disorders, such as schizophrenia and autism. In addition, we recently found larger numbers of ectopic neurons in the white matter in human extremely preterm infant brains (born before 28 gestational weeks) with brain injury. Extremely preterm infants frequently develop cognitive impairment in later life. The reason why cognitive impairment is a common neurological outcome following ischemic brain injury in extremely preterm infants remains unknown. In this study, we investigated whether abnormal cytological architectures might be involved in the pathogenesis of the cognitive impairment that often develops later in extremely preterm infants with brain injury. We sought to establish a mouse model of extremely preterm infants with brain injuries and produced ischemic brain damage in mouse embryos by occluding the maternal uterine arteries. The mice showed abnormal cytological architectures with ectopic neurons in the white matter, altered neuronal alignment, and abnormal cortico-cortical axonal wiring. Similar to humans with brain injury, the surviving mice exhibited cognitive deficits. To further elucidate the pathological mechanisms of the abnormal cytological architectures, we generated mouse models with ectopic neurons by inducing focal heterotopias with the in utero electroporation technique. The mice with focal heterotopias also exhibited cognitive deficits. The pathological mechanisms of the abnormal cytological architectures with ectopic neurons will be discussed.		3O1-4 Effects of lateral olfactory tract stimulation on brain Fos immunoreactivity in vasopressin neurons of the rat piriform cortex Chiharu Tsuji，Takahiro Tsuji，Andrew Allchorne，Gareth Leng，Ludwig Mike Centre for Integrative Physiology, University of Edinburgh In the main olfactory system, odours are perceived at the main olfactory epithelium, then passed on to main olfactory bulb (MOB) and subsequently to the anterior olfactory nucleus (AON), the piriform cortex (PC) and the cortical amygdala. Previously, we reported populations of vasopressin neurons exist in different areas of the rat olfactory system, such as MOB, accessory olfactory bulb (AOB) and the AON and showed that these are involved in the coding of social odour information. Utilizing immunohistochemistry and a transgenic rat in which an enhanced green fluorescent protein reporter gene is expressed in vasopressin neurons (eGFP-vasopressin), we show here a population of vasopressin neurones in the piriform cortex (PC). There is no sex difference in the number of neurons expressing vasopressin. The vasopressin neurones are predominantly located in the superficial layer 2 and the majority of these neurons co-express the excitatory transmitter glutamate. We analysed the immediate early gene product, Fos, to examine whether stimulation of the olfactory system activates the vasopressin neurons in different parts of the olfactory system. Electrical stimulation of the lateral olfactory tract (LOT) leads to a significantly increases in the number of Fos-positive nuclei in the PC, MOB, AOB, dorsal AON, and supraoptic nucleus (SON). However, there was only a significant increase in Fos expression in vasopressin cells of the PC. These data indicate that, out of vasopressinergic olfactory system, olfactory direct input activates only the vasopressin cells in piriform cortex.