Social behaviors are crucial for gregarious animals,including humans.In order to exhibit appropriate behaviors in a complex social context,such as mating,aggression,avoidance,and cooperation,individuals need to rememb...Social behaviors are crucial for gregarious animals,including humans.In order to exhibit appropriate behaviors in a complex social context,such as mating,aggression,avoidance,and cooperation,individuals need to remember their previous experiences with other members and accurately recognize them when they meet again.This ability is called“social memory”[1].Many psychiatric disorders in humans,such as autism spectrum disorder,attention deficit hyperactivity disorder,and schizophrenia,are characterized by social memory impairments.Patients with these disorders,along with corresponding animal models,often show defects associated with the thalamic reticular nucleus(TRN).The TRN,a thin layer of neurons surrounding the thalamus,mainly regulates and coordinates the transfer of information between the cortex and the thalamus,playing a role in higher brain functions such as consciousness,attention,and sensory processing.However,whether the TRN is involved in social memory remains unknown.展开更多
Background:Episodic memory loss is a prominent clinical manifestation of Alzheimer’s disease(AD),which is closely related to tau pathology and hippocampal impairment.Due to the heterogeneity of brain neurons,the spec...Background:Episodic memory loss is a prominent clinical manifestation of Alzheimer’s disease(AD),which is closely related to tau pathology and hippocampal impairment.Due to the heterogeneity of brain neurons,the specific roles of different brain neurons in terms of their sensitivity to tau accumulation and their contribution to AD-like social memory loss remain unclear.Therefore,further investigation is necessary.Methods:We investigated the effects of AD-like tau pathology by Tandem mass tag proteomic and phosphoproteomic analysis,social behavioural tests,hippocampal electrophysiology,immunofluorescence staining and in vivo optical fibre recording of GCaMP6f and iGABASnFR.Additionally,we utilized optogenetics and administered ursolic acid(UA)via oral gavage to examine the effects of these agents on social memory in mice.Results:The results of proteomic and phosphoproteomic analyses revealed the characteristics of ventral hippocampal CA1(vCA1)under both physiological conditions and AD-like tau pathology.As tau progressively accumulated,vCA1,especially its excitatory and parvalbumin(PV)neurons,were fully filled with mislocated and phosphorylated tau(p-Tau).This finding was not observed for dorsal hippocampal CA1(dCA1).The overexpression of human tau(hTau)in excitatory and PV neurons mimicked AD-like tau accumulation,significantly inhibited neuronal excitability and suppressed distinct discrimination-associated firings of these neurons within vCA1.Photoactivating excitatory and PV neurons in vCA1 at specific rhythms and time windows efficiently ameliorated tau-impaired social memory.Notably,1 month of UA administration efficiently decreased tau accumulation via autophagy in a transcription factor EB(TFEB)-dependent manner and restored the vCA1 microcircuit to ameliorate tau-impaired social memory.Conclusion:This study elucidated distinct protein and phosphoprotein networks between dCA1 and vCA1 and highlighted the susceptibility of the vCA1 microcircuit to AD-like tau accumulation.Notably,our novel findings regarding the efficacy of UA in reducing tau load and targeting the vCA1 microcircuit may provide a promising strategy for treating AD in the future.展开更多
Chronic stress may disrupt the normal neurodevelopmental trajectory of the adolescent brain(especially the prefrontal cortex) and contribute to the pathophysiology of stress-related mental illnesses,but the underlying...Chronic stress may disrupt the normal neurodevelopmental trajectory of the adolescent brain(especially the prefrontal cortex) and contribute to the pathophysiology of stress-related mental illnesses,but the underlying molecular mechanisms remain unclear.Here,we investigated how synaptic cell adhesion molecules(e.g.,nectin3)are involved in the effects of adolescent chronic stress on mouse medial prefrontal cortex(mPFC).Male C57BL/6N mice were subjected to chronic social instability stress from postnatal days 29 to 77.One week later,the mice exposed to chronic stress exhibited impaired social recognition and spatial working memory,simplified dendritic structure,and reduced spine density in the mPFC.Membrane localization of nectin3 was also altered,and was significantly correlated with behavioral performance.Furthermore,knocking down mPFC nectin3 expression by adeno-associated virus in adolescent mice reproduced the stress-induced changes in behavior and mPFC morphology.These results support the hypothesis that nectin3 is a potential mediator of the effects of adolescent chronic stress on prefrontal structural and functional abnormalities.展开更多
Cerebral ischemia/reperfusion injury impairs learning and memory in patients.Studies have shown that synaptic function is involved in the formation and development of memory,and that DNA methylation plays a key role i...Cerebral ischemia/reperfusion injury impairs learning and memory in patients.Studies have shown that synaptic function is involved in the formation and development of memory,and that DNA methylation plays a key role in the regulation of learning and memory.To investigate the role of DNA hypomethylation in cerebral ischemia/reperfusion injury,in this study,we established a rat model of cerebral ischemia/reperfusion injury by occlusion of the middle cerebral artery and then treated the rats with intraperitoneal 5-aza-2′-deoxycytidine,an inhibitor of DNA methylation.Our results showed that 5-aza-2′-deoxycytidine markedly improved the neurological function,and cognitive,social and spatial memory abilities,and dose-dependently increased the synaptic density and the expression of SYP and SHANK2 proteins in the hippocampus in a dose-dependent manner in rats with cerebral ischemia/reperfusion injury.The effects of 5-aza-2′-deoxycytidine were closely related to its reduction of genomic DNA methylation and DNA methylation at specific sites of the Syp and Shank2 genes in rats with cerebral ischemia/reperfusion injury.These findings suggest that inhibition of DNA methylation by 5-aza-2′-deoxycytidine promotes the recovery of learning and memory impairment in a rat model of cerebral ischemia/reperfusion injury.These results provide theoretical evidence for stroke treatment using epigenetic methods.展开更多
In this paper, the network movie as the research object, quoted in the theory of ＂collective memory＂ from Mauric Halbwachs, the academic circles in recent years on the Internet Movie different viewpoint for referenc...In this paper, the network movie as the research object, quoted in the theory of ＂collective memory＂ from Mauric Halbwachs, the academic circles in recent years on the Internet Movie different viewpoint for reference, consult a lot of literatures, the method of interdisciplinary research in the field of psychology, culture, to ＂memory＂, ＂culture＂, ＂group （SOCIAL）＂ in three aspects, analysis of network movie as an expression of individual consciousness, contradiction between individual and collective in the expression of the collective memory of the film, through the analysis of the network specific expression, expression, the expression of an important role in the formation of rebellious sense for people aesthetic psychology, the awakening of individual consciousness and group identity. Therefore, it is necessary to culture the appearance and development of Internet Movie, is bound to the mode of expression, the people＇s cultural psychology and social individual to collective identity have significant influence.展开更多
The geographical environment of the Zhaozhou Basin provides diverse possibilities for the formation and evolution of vernacular settlements and architectural spaces within multi-ethnic communities.Taking the vernacula...The geographical environment of the Zhaozhou Basin provides diverse possibilities for the formation and evolution of vernacular settlements and architectural spaces within multi-ethnic communities.Taking the vernacular settlements and architecture of the Zhaozhou Basin as a case study,this research adopts the anthropological concept of the“Bazi Society”as an analytical framework,and integrates the methodology of“social memory”to explore the social mechanisms that shape regional architectural space.By utilizing the“social memory”research approach,this study integrates GIS image analysis,social memory indicator surveys,oral interviews,and local historical materials from the Ming and Qing Dynasties,including local chronicles,historical maps,and illustrations,along with data from the Republican era,to conduct an in-depth investigation of typical settlements in the Zhaozhou Basin.This study proposes a“rule of in-depth memory depiction”,which is structured around three elements:the research objects(settlement spaces,public temples,and vernacular dwellings),the analytical dimensions(spatial patterns,cultural practices,and collective memory),and the narrative methods(oral testimony,schematic mapping,and quantitative indicators),thereby providing a clear framework for its application.It analyzes the feasibility of the research pathway for the“Bazi Society of basins”.The results can be summarized in three points.(1)Based on field investigation and GIS-historical triangulation,151 valid questionnaires yielded five principal memory factors(communalities>0.8;cumulative variance contribution rate 85.66%),thus verifying the operational feasibility and quantitative validity of the“Thick Description of Memory”framework.(2)Settlements in the Zhaozhou Basin exhibit a significant“landform-function-memory coupling pattern”,which reveals the continuous reconstruction of power structures and spatial forms within the processes of social memory.(3)Despite their functional transformations,public temples continue to serve as the spiritual cores of communities and as explicit carriers of collective memory,so they reflect the material continuity of productive and everyday life memories.Overall,this study demonstrates that“social memory functions as a key mediating mechanism”linking geographical environment,social practice,and vernacular architectural space,which provides new theoretical and methodological support for understanding the evolutionary logic of basin settlements and for guiding cultural heritage renewal.展开更多
基金supported by grants from the National Natural Science Foundation of China(32125018 and 32071005)Zhejiang Provincial Natural Science Foundation of China(LD24H090002)+3 种基金Nanhu Brain-computer Interface Institute(010904008)Innovative Research Team of High-level Local Universities in Shanghai(SHSMUZDCX20211102)Fundamental Research Funds for the Central Universities(226-2024-00133)the MOE Frontiers Science Center for Brain Science&Brain-Machine Integration of Zhejiang University.
文摘Social behaviors are crucial for gregarious animals,including humans.In order to exhibit appropriate behaviors in a complex social context,such as mating,aggression,avoidance,and cooperation,individuals need to remember their previous experiences with other members and accurately recognize them when they meet again.This ability is called“social memory”[1].Many psychiatric disorders in humans,such as autism spectrum disorder,attention deficit hyperactivity disorder,and schizophrenia,are characterized by social memory impairments.Patients with these disorders,along with corresponding animal models,often show defects associated with the thalamic reticular nucleus(TRN).The TRN,a thin layer of neurons surrounding the thalamus,mainly regulates and coordinates the transfer of information between the cortex and the thalamus,playing a role in higher brain functions such as consciousness,attention,and sensory processing.However,whether the TRN is involved in social memory remains unknown.
基金supported in part by the National Natural Science Foundation of China(91949205,82071219,82001134,31730035,81721005,and 82201584)the Hubei Provincial Key S&T Program(2018ACA142)the Guangdong Provincial Key S&T Program(2018B030336001).
文摘Background:Episodic memory loss is a prominent clinical manifestation of Alzheimer’s disease(AD),which is closely related to tau pathology and hippocampal impairment.Due to the heterogeneity of brain neurons,the specific roles of different brain neurons in terms of their sensitivity to tau accumulation and their contribution to AD-like social memory loss remain unclear.Therefore,further investigation is necessary.Methods:We investigated the effects of AD-like tau pathology by Tandem mass tag proteomic and phosphoproteomic analysis,social behavioural tests,hippocampal electrophysiology,immunofluorescence staining and in vivo optical fibre recording of GCaMP6f and iGABASnFR.Additionally,we utilized optogenetics and administered ursolic acid(UA)via oral gavage to examine the effects of these agents on social memory in mice.Results:The results of proteomic and phosphoproteomic analyses revealed the characteristics of ventral hippocampal CA1(vCA1)under both physiological conditions and AD-like tau pathology.As tau progressively accumulated,vCA1,especially its excitatory and parvalbumin(PV)neurons,were fully filled with mislocated and phosphorylated tau(p-Tau).This finding was not observed for dorsal hippocampal CA1(dCA1).The overexpression of human tau(hTau)in excitatory and PV neurons mimicked AD-like tau accumulation,significantly inhibited neuronal excitability and suppressed distinct discrimination-associated firings of these neurons within vCA1.Photoactivating excitatory and PV neurons in vCA1 at specific rhythms and time windows efficiently ameliorated tau-impaired social memory.Notably,1 month of UA administration efficiently decreased tau accumulation via autophagy in a transcription factor EB(TFEB)-dependent manner and restored the vCA1 microcircuit to ameliorate tau-impaired social memory.Conclusion:This study elucidated distinct protein and phosphoprotein networks between dCA1 and vCA1 and highlighted the susceptibility of the vCA1 microcircuit to AD-like tau accumulation.Notably,our novel findings regarding the efficacy of UA in reducing tau load and targeting the vCA1 microcircuit may provide a promising strategy for treating AD in the future.
基金supported by the National Natural Science Foundation of China(81401129,81571321,81630031,and 81571312)the Peking University Medicine Seed Fund for Interdisciplinary Research (BMU2017MX021)+1 种基金the National Key Basic Research Program of China (2015CB856401)the Beijing Brain Project (Z171100000117016)。
文摘Chronic stress may disrupt the normal neurodevelopmental trajectory of the adolescent brain(especially the prefrontal cortex) and contribute to the pathophysiology of stress-related mental illnesses,but the underlying molecular mechanisms remain unclear.Here,we investigated how synaptic cell adhesion molecules(e.g.,nectin3)are involved in the effects of adolescent chronic stress on mouse medial prefrontal cortex(mPFC).Male C57BL/6N mice were subjected to chronic social instability stress from postnatal days 29 to 77.One week later,the mice exposed to chronic stress exhibited impaired social recognition and spatial working memory,simplified dendritic structure,and reduced spine density in the mPFC.Membrane localization of nectin3 was also altered,and was significantly correlated with behavioral performance.Furthermore,knocking down mPFC nectin3 expression by adeno-associated virus in adolescent mice reproduced the stress-induced changes in behavior and mPFC morphology.These results support the hypothesis that nectin3 is a potential mediator of the effects of adolescent chronic stress on prefrontal structural and functional abnormalities.
基金supported by the National Natural Science Foundation of China,No.82101567Doctoral Start-up Foundation of Liaoning Province,No.2021-BS-111345 Talent Project of Shengjing Hospital of China Medical University,No.M0673(all to XYF)。
文摘Cerebral ischemia/reperfusion injury impairs learning and memory in patients.Studies have shown that synaptic function is involved in the formation and development of memory,and that DNA methylation plays a key role in the regulation of learning and memory.To investigate the role of DNA hypomethylation in cerebral ischemia/reperfusion injury,in this study,we established a rat model of cerebral ischemia/reperfusion injury by occlusion of the middle cerebral artery and then treated the rats with intraperitoneal 5-aza-2′-deoxycytidine,an inhibitor of DNA methylation.Our results showed that 5-aza-2′-deoxycytidine markedly improved the neurological function,and cognitive,social and spatial memory abilities,and dose-dependently increased the synaptic density and the expression of SYP and SHANK2 proteins in the hippocampus in a dose-dependent manner in rats with cerebral ischemia/reperfusion injury.The effects of 5-aza-2′-deoxycytidine were closely related to its reduction of genomic DNA methylation and DNA methylation at specific sites of the Syp and Shank2 genes in rats with cerebral ischemia/reperfusion injury.These findings suggest that inhibition of DNA methylation by 5-aza-2′-deoxycytidine promotes the recovery of learning and memory impairment in a rat model of cerebral ischemia/reperfusion injury.These results provide theoretical evidence for stroke treatment using epigenetic methods.
文摘In this paper, the network movie as the research object, quoted in the theory of ＂collective memory＂ from Mauric Halbwachs, the academic circles in recent years on the Internet Movie different viewpoint for reference, consult a lot of literatures, the method of interdisciplinary research in the field of psychology, culture, to ＂memory＂, ＂culture＂, ＂group （SOCIAL）＂ in three aspects, analysis of network movie as an expression of individual consciousness, contradiction between individual and collective in the expression of the collective memory of the film, through the analysis of the network specific expression, expression, the expression of an important role in the formation of rebellious sense for people aesthetic psychology, the awakening of individual consciousness and group identity. Therefore, it is necessary to culture the appearance and development of Internet Movie, is bound to the mode of expression, the people＇s cultural psychology and social individual to collective identity have significant influence.
基金The National Natural Science Foundation of China(52478058)The 2025 Yunnan Provincial Philosophy and Social Science Planning Annual Project(QN202522)。
文摘The geographical environment of the Zhaozhou Basin provides diverse possibilities for the formation and evolution of vernacular settlements and architectural spaces within multi-ethnic communities.Taking the vernacular settlements and architecture of the Zhaozhou Basin as a case study,this research adopts the anthropological concept of the“Bazi Society”as an analytical framework,and integrates the methodology of“social memory”to explore the social mechanisms that shape regional architectural space.By utilizing the“social memory”research approach,this study integrates GIS image analysis,social memory indicator surveys,oral interviews,and local historical materials from the Ming and Qing Dynasties,including local chronicles,historical maps,and illustrations,along with data from the Republican era,to conduct an in-depth investigation of typical settlements in the Zhaozhou Basin.This study proposes a“rule of in-depth memory depiction”,which is structured around three elements:the research objects(settlement spaces,public temples,and vernacular dwellings),the analytical dimensions(spatial patterns,cultural practices,and collective memory),and the narrative methods(oral testimony,schematic mapping,and quantitative indicators),thereby providing a clear framework for its application.It analyzes the feasibility of the research pathway for the“Bazi Society of basins”.The results can be summarized in three points.(1)Based on field investigation and GIS-historical triangulation,151 valid questionnaires yielded five principal memory factors(communalities>0.8;cumulative variance contribution rate 85.66%),thus verifying the operational feasibility and quantitative validity of the“Thick Description of Memory”framework.(2)Settlements in the Zhaozhou Basin exhibit a significant“landform-function-memory coupling pattern”,which reveals the continuous reconstruction of power structures and spatial forms within the processes of social memory.(3)Despite their functional transformations,public temples continue to serve as the spiritual cores of communities and as explicit carriers of collective memory,so they reflect the material continuity of productive and everyday life memories.Overall,this study demonstrates that“social memory functions as a key mediating mechanism”linking geographical environment,social practice,and vernacular architectural space,which provides new theoretical and methodological support for understanding the evolutionary logic of basin settlements and for guiding cultural heritage renewal.
