Fear memory contextualization is critical for selecting adaptive behavior to survive.Contextual fear conditioning(CFC)is a classical model for elucidating related underlying neuronal circuits.The primary visual cortex...Fear memory contextualization is critical for selecting adaptive behavior to survive.Contextual fear conditioning(CFC)is a classical model for elucidating related underlying neuronal circuits.The primary visual cortex(V1)is the primary cortical region for contextual visual inputs,but its role in CFC is poorly understood.Here,our experiments demonstrated that bilateral inactivation of V1 in mice impaired CFC retrieval,and both CFC learning and extinction increased the turnover rate of axonal boutons in V1.The frequency of neuronal Ca^(2+)activity decreased after CFC learning,while CFC extinction reversed the decrease and raised it to the naïve level.Contrary to control mice,the frequency of neuronal Ca^(2+)activity increased after CFC learning in microglia-depleted mice and was maintained after CFC extinction,indicating that microglial depletion alters CFC learning and the frequency response pattern of extinction-induced Ca^(2+)activity.These findings reveal a critical role of microglia in neocortical information processing in V1,and suggest potential approaches for cellular-based manipulation of acquired fear memory.展开更多
Accumulating evidence indicates that inhalation anesthetics induce or increase the risk of cognitive impairment. GLYX-13（rapastinel） acts on the glycine site of N-methyl-D-aspartate receptors（NMDARs） and has been ...Accumulating evidence indicates that inhalation anesthetics induce or increase the risk of cognitive impairment. GLYX-13（rapastinel） acts on the glycine site of N-methyl-D-aspartate receptors（NMDARs） and has been shown to enhance hippocampus-dependent learning and memory function. However, the mechanisms by which GLYX-13 affects learning and memory function are still unclear. In this study, we investigated these mechanisms in a mouse model of long-term anesthesia exposure. Mice were intravenously administered 1 mg/kg GLYX-13 at 2 hours before isoflurane exposure（1.5% for 6 hours）. Cognitive function was assessed using the contextual fear conditioning test and the novel object recognition test. The mRNA expression and phosphorylated protein levels of NMDAR pathway components, N-methyl-D-aspartate receptor subunit 2B（NR2B）-Ca2+/calmodulin dependent protein kinase II（CaMKII）-cyclic adenosine monophosphate response element binding protein（CREB）, in the hippocampus were evaluated by quantitative RT-PCR and western blot assay. Pretreatment with GLYX-13 ameliorated isoflurane exposure-induced cognitive impairment and restored NR2B, CaMKII and CREB mRNA and phosphorylated protein levels. Intracerebroventricular injection of KN93, a selective CaMKII inhibitor, significantly diminished the effect of GLYX-13 on cognitive function and NR2B, CaMKII and CREB levels in the hippocampus. Taken together, our findings suggest that GLYX-13 pretreatment alleviates isoflurane-induced cognitive dysfunction by protecting against perturbation of the NR2B/CaMKII/CREB signaling pathway in the hippocampus. Therefore, GLYX-13 may have therapeutic potential for the treatment of anesthesia-induced cognitive dysfunction. This study was approved by the Experimental Animal Ethics Committee of Drum Tower Hospital affiliated to the Medical College of Nanjing University, China（approval No. 20171102） on November 20, 2017.展开更多
Communicational and international developments have different aspects in today＇s world so that some terms like ＂Internationalization,＂ ＂Liberalization,＂ ＂Universalization,＂ ＂Westernization,＂ ＂Deterritorializ...Communicational and international developments have different aspects in today＇s world so that some terms like ＂Internationalization,＂ ＂Liberalization,＂ ＂Universalization,＂ ＂Westernization,＂ ＂Deterritorialization＂ find interferences in social sciences and humanities studies. But these terms can generally be distinguished by two different categories of study as some experts have emphasized that the above developments are in the process （Globalization） while the others considered them on the project （To Globalize）. The main problem is that how we can find out the focal point of both studies through which the accuracy of these claims to be verified to know whether contemporary changes and evolutions are formed in a process or a project. It seems that the focal point in the sphere of both claims （processes and projects） is the issue of ＂identity＂ since both spheres agree that the concept of ＂identity＂ has passed a series of changes and developments, although each one renders the path and goal of ＂identity＂ changes by its own specific interpretations. In this article, we claim that using linguistic approach we are able to review the developments and evolutions＇ flow of identity in the present era and thereby it can be found that the developments in information and communication would lead to creating a process in the context of Globalization or a project on Universalization. The assumption of this study is that by explanation of the above-mentioned situation, we can see that based on the linguistic approach, the process of making identity is ＂context-based＂ and ＂conditional＂ as opposed to a project view formation and relative continuity of identification process would generally be subject to the condition.展开更多
基金supported by the National Natural Science Foundation of China(61735016)the Natural Science Foundation of Zhejiang Province(LR20F050002)+3 种基金the Key R&D Program of Zhejiang Province(2020C03009 and 2021C03001)the Zhejiang Leading Innovation and Entrepreneurship Team(202099144)the CAMS Innovation Fund for Medical Sciences(2019-I2M-5-057)Fundamental Research Funds for the Central Universities.
文摘Fear memory contextualization is critical for selecting adaptive behavior to survive.Contextual fear conditioning(CFC)is a classical model for elucidating related underlying neuronal circuits.The primary visual cortex(V1)is the primary cortical region for contextual visual inputs,but its role in CFC is poorly understood.Here,our experiments demonstrated that bilateral inactivation of V1 in mice impaired CFC retrieval,and both CFC learning and extinction increased the turnover rate of axonal boutons in V1.The frequency of neuronal Ca^(2+)activity decreased after CFC learning,while CFC extinction reversed the decrease and raised it to the naïve level.Contrary to control mice,the frequency of neuronal Ca^(2+)activity increased after CFC learning in microglia-depleted mice and was maintained after CFC extinction,indicating that microglial depletion alters CFC learning and the frequency response pattern of extinction-induced Ca^(2+)activity.These findings reveal a critical role of microglia in neocortical information processing in V1,and suggest potential approaches for cellular-based manipulation of acquired fear memory.
基金supported by the National Natural Science Foundation of China,No.81730033(to XPG),81701371(to TJX),81801380(to XZ)Natural Science Foundation of Jiangsu Province of China,No.BK20170654(to TJX),BK20170129(to XZ)
文摘Accumulating evidence indicates that inhalation anesthetics induce or increase the risk of cognitive impairment. GLYX-13（rapastinel） acts on the glycine site of N-methyl-D-aspartate receptors（NMDARs） and has been shown to enhance hippocampus-dependent learning and memory function. However, the mechanisms by which GLYX-13 affects learning and memory function are still unclear. In this study, we investigated these mechanisms in a mouse model of long-term anesthesia exposure. Mice were intravenously administered 1 mg/kg GLYX-13 at 2 hours before isoflurane exposure（1.5% for 6 hours）. Cognitive function was assessed using the contextual fear conditioning test and the novel object recognition test. The mRNA expression and phosphorylated protein levels of NMDAR pathway components, N-methyl-D-aspartate receptor subunit 2B（NR2B）-Ca2+/calmodulin dependent protein kinase II（CaMKII）-cyclic adenosine monophosphate response element binding protein（CREB）, in the hippocampus were evaluated by quantitative RT-PCR and western blot assay. Pretreatment with GLYX-13 ameliorated isoflurane exposure-induced cognitive impairment and restored NR2B, CaMKII and CREB mRNA and phosphorylated protein levels. Intracerebroventricular injection of KN93, a selective CaMKII inhibitor, significantly diminished the effect of GLYX-13 on cognitive function and NR2B, CaMKII and CREB levels in the hippocampus. Taken together, our findings suggest that GLYX-13 pretreatment alleviates isoflurane-induced cognitive dysfunction by protecting against perturbation of the NR2B/CaMKII/CREB signaling pathway in the hippocampus. Therefore, GLYX-13 may have therapeutic potential for the treatment of anesthesia-induced cognitive dysfunction. This study was approved by the Experimental Animal Ethics Committee of Drum Tower Hospital affiliated to the Medical College of Nanjing University, China（approval No. 20171102） on November 20, 2017.
文摘Communicational and international developments have different aspects in today＇s world so that some terms like ＂Internationalization,＂ ＂Liberalization,＂ ＂Universalization,＂ ＂Westernization,＂ ＂Deterritorialization＂ find interferences in social sciences and humanities studies. But these terms can generally be distinguished by two different categories of study as some experts have emphasized that the above developments are in the process （Globalization） while the others considered them on the project （To Globalize）. The main problem is that how we can find out the focal point of both studies through which the accuracy of these claims to be verified to know whether contemporary changes and evolutions are formed in a process or a project. It seems that the focal point in the sphere of both claims （processes and projects） is the issue of ＂identity＂ since both spheres agree that the concept of ＂identity＂ has passed a series of changes and developments, although each one renders the path and goal of ＂identity＂ changes by its own specific interpretations. In this article, we claim that using linguistic approach we are able to review the developments and evolutions＇ flow of identity in the present era and thereby it can be found that the developments in information and communication would lead to creating a process in the context of Globalization or a project on Universalization. The assumption of this study is that by explanation of the above-mentioned situation, we can see that based on the linguistic approach, the process of making identity is ＂context-based＂ and ＂conditional＂ as opposed to a project view formation and relative continuity of identification process would generally be subject to the condition.
