Numerous studies on the formation and consolidation of memory have shown that memory processes are characterized by phase-dependent and dynamic regulation.Memory retrieval,as the only representation of memory content ...Numerous studies on the formation and consolidation of memory have shown that memory processes are characterized by phase-dependent and dynamic regulation.Memory retrieval,as the only representation of memory content and an active form of memory processing that induces memory reconsolidation,has attracted increasing attention in recent years.Although the molecular mechanisms specifc to memory retrievalinduced reconsolidation have been gradually revealed,an understanding of the time-dependent regulatory mechanisms of this process is still lacking.In this study,we applied a transcriptome analysis of memory retrieval at diferent time points in the recent memory stage.Diferential expression analysis and Short Time-series Expression Miner(STEM)depicting temporal gene expression patterns indicated that most diferential gene expression occurred at 48 h,and the STEM cluster showing the greatest transcriptional upregulation at 48 h demonstrated the most significant diference.We then screened the diferentially-expressed genes associated with that met the expression patterns of those cluster-identifed genes that have been reported to be involved in learning and memory processes in addition to dipeptidyl peptidase 9(DPP9).Further quantitative polymerase chain reaction verifcation and pharmacological intervention suggested that DPP9 is involved in 48-h fear memory retrieval and viral vector-mediated overexpression of DPP9 countered the 48-h retrieval-induced attenuation of fear memory.Taken together,our fndings suggest that temporal gene expression patterns are induced by recent memory retrieval and provide hitherto undocumented evidence of the role of DPP9 in the retrieval-induced reconsolidation of fear memory.展开更多
Abundant evidence indicates that propofol profoundly affects memory processes, although its specific effects on memory retrieval have not been clarified. A recent study has indicated that hippocampal glycogen synthase...Abundant evidence indicates that propofol profoundly affects memory processes, although its specific effects on memory retrieval have not been clarified. A recent study has indicated that hippocampal glycogen synthase kinase-3β（GSK-3β） activity affects memory. Constitutively active GSK-3β is required for memory retrieval, and propofol has been shown to inhibit GSK-3β. Thus, the present study examined whether propofol affects memory retrieval, and, if so, whether that effect is mediated through altered GSK-3β activity. Adult Sprague-Dawley rats were trained on a Morris water maze task（eight acquisition trials in one session） and subjected under the influence of a subhypnotic dose of propofol to a 24-hour probe trial memory retrieval test. The results showed that rats receiving pretest propofol（25 mg/kg） spent significantly less time in the target quadrant but showed no change in locomotor activity compared with those in the control group. Memory retrieval was accompanied by reduced phosphorylation of the serine-9 residue of GSK-3β in the hippocampus, whereas phosphorylation of the tyrosine-216 residue was unaffected. However, propofol blocked this retrieval-associated serine-9 phosphorylation. These findings suggest that subhypnotic propofol administration impairs memory retrieval and that the amnestic effects of propofol may be mediated by attenuated GSK-3β signaling in the hippocampus.展开更多
DDeeaarr EEddiittoorr,,The encoding and retrieval of emotional memories demands intricate interplay within the limbic network,where the network state is subject to significant reconfiguration by learning-induced plast...DDeeaarr EEddiittoorr,,The encoding and retrieval of emotional memories demands intricate interplay within the limbic network,where the network state is subject to significant reconfiguration by learning-induced plasticity,behavioral state,and contextual information[1].展开更多
The raphe nucleus is critical for feeding, rewarding and memory. However, how the heterogenous raphe neurons are molecularly and structurally organized to engage their divergent functions remains unknown. Here, we gen...The raphe nucleus is critical for feeding, rewarding and memory. However, how the heterogenous raphe neurons are molecularly and structurally organized to engage their divergent functions remains unknown. Here, we genetically target a subset of neurons expressing VGLUT3. VGLUT3 neurons control the efficacy of spatial memory retrieval by synapsing directly with parvalbumin-expressing GABA interneurons(PGIs) in the dentate gyrus. In a mouse model of Alzheimer's disease(AD mice),VGLUT3→PGIs synaptic transmission is impaired by ETV4 inhibition of VGLUT3 transcription. ETV4 binds to a promoter region of VGLUT3 and activates VGLUT3 transcription in VGLUT3 neurons. Strengthening VGLUT3→PGIs synaptic transmission by ETV4 activation of VGLUT3 transcription upscales the efficacy of spatial memory retrieval in AD mice. This study reports a novel circuit and molecular mechanism underlying the efficacy of spatial memory retrieval via ETV4 inhibition of VGLUT3 transcription and hence provides a promising target for therapeutic intervention of the disease progression.展开更多
The mushroom body(MB),a bilateral brain structure pos-sessing about 2000-2500 neurons per hemisphere,plays a central role in olfactory learning and memory in Dros-ophila melanogaster.Extensive studies have demonstrat-...The mushroom body(MB),a bilateral brain structure pos-sessing about 2000-2500 neurons per hemisphere,plays a central role in olfactory learning and memory in Dros-ophila melanogaster.Extensive studies have demonstrat-ed that three major types of MB neurons(α/β,α’/β’andγ)exhibit distinct functions in memory processing,including the critical role of approximately 1000 MBα/βneurons in retrieving long-term memory.Inspired by recent fi ndings that MBα/βneurons can be further divided into three subdivisions(surface,posterior and core)and wherein theα/βcore neurons play an permissive role in long-term memory consolidation,we examined the functional differ-ences of all the three morphological subdivisions of MBα/βby temporally precise manipulation of their synaptic outputs during long-term memory retrieval.We found the normal neurotransmission from a combination of MBα/βsurface and posterior neurons is necessary for retrieving both aversive and appetitive long-term memory,whereas output from MBα/βposterior or core subdivision alone is dispensable.These results imply a specifi c requirement of about 500 MBα/βneurons in supporting long-term memory retrieval and a further functional partitioning for memory processing within the MBα/βregion.展开更多
Neural degeneration and regeneration are important topics in neurological diseases. There are limited options for therapeutic interventions in neurological diseases that provide simultaneous spatial and temporal contr...Neural degeneration and regeneration are important topics in neurological diseases. There are limited options for therapeutic interventions in neurological diseases that provide simultaneous spatial and temporal control of neurons. This drawback increases side effects due to non-specific targeting. Optogenetics is a technology that allows precise spatial and temporal control of cells. Therefore, this technique has high potential as a therapeutic strategy for neurological diseases. Even though the application of optogenetics in understanding brain functional organization and complex behaviour states have been elaborated, reviews of its therapeutic potential especially in neurodegeneration and regeneration are still limited. This short review presents representative work in optogenetics in disease models such as spinal cord injury, multiple sclerosis, epilepsy, Alzheimer＇s disease and Parkinson＇s disease. It is aimed to provide a broader perspective on optogenetic therapeutic potential in neurodegeneration and neural regeneration.展开更多
Artificial photonic synapses have set off a new upsurge for mimicking a series of neural activities in recent years.In particular,the investigation of learning and memory behaviors with pressure or emotion and corresp...Artificial photonic synapses have set off a new upsurge for mimicking a series of neural activities in recent years.In particular,the investigation of learning and memory behaviors with pressure or emotion and corresponding mechanisms is currently the focus of more attention.Herein,a hippocampus-inspired device based on MoS_(2)for illumination time encoding is fabricated,in which the encryption technology is employed for data security.In addition,the pressureinduced memory behaviors with full memory function(memory trace)over time such as encoding,storage and retrieval are demonstrated,resulting from the decreasing positive photocurrent of the MoS;devices.The proposed mechanism of the memory effect when exposed to the light is elucidated in detail.Moreover,the effect of stress hormone on memory behavior is displayed via different illumination time periods and light intensities.These results indicate the potential application of MoS_(2)devices in artificial neural network.展开更多
基金supported by the STI2030-Major Projects(2022ZD0204900)the National Natural Science Foundation of China(32071029 and 32271080)+1 种基金the Strategic Priority Research Program of the Chinese Academy of Sciences(XDB32020200)the Yunnan Provincial Science and Technology Department(202402AA310014).
文摘Numerous studies on the formation and consolidation of memory have shown that memory processes are characterized by phase-dependent and dynamic regulation.Memory retrieval,as the only representation of memory content and an active form of memory processing that induces memory reconsolidation,has attracted increasing attention in recent years.Although the molecular mechanisms specifc to memory retrievalinduced reconsolidation have been gradually revealed,an understanding of the time-dependent regulatory mechanisms of this process is still lacking.In this study,we applied a transcriptome analysis of memory retrieval at diferent time points in the recent memory stage.Diferential expression analysis and Short Time-series Expression Miner(STEM)depicting temporal gene expression patterns indicated that most diferential gene expression occurred at 48 h,and the STEM cluster showing the greatest transcriptional upregulation at 48 h demonstrated the most significant diference.We then screened the diferentially-expressed genes associated with that met the expression patterns of those cluster-identifed genes that have been reported to be involved in learning and memory processes in addition to dipeptidyl peptidase 9(DPP9).Further quantitative polymerase chain reaction verifcation and pharmacological intervention suggested that DPP9 is involved in 48-h fear memory retrieval and viral vector-mediated overexpression of DPP9 countered the 48-h retrieval-induced attenuation of fear memory.Taken together,our fndings suggest that temporal gene expression patterns are induced by recent memory retrieval and provide hitherto undocumented evidence of the role of DPP9 in the retrieval-induced reconsolidation of fear memory.
基金financially supported by the National Natural Science Foundation of China,No.81571039the Foundation for Fostering the National Natural Science Foundation of First Affiliated Hospital of Anhui Medical University in China,No.2015KJ12
文摘Abundant evidence indicates that propofol profoundly affects memory processes, although its specific effects on memory retrieval have not been clarified. A recent study has indicated that hippocampal glycogen synthase kinase-3β（GSK-3β） activity affects memory. Constitutively active GSK-3β is required for memory retrieval, and propofol has been shown to inhibit GSK-3β. Thus, the present study examined whether propofol affects memory retrieval, and, if so, whether that effect is mediated through altered GSK-3β activity. Adult Sprague-Dawley rats were trained on a Morris water maze task（eight acquisition trials in one session） and subjected under the influence of a subhypnotic dose of propofol to a 24-hour probe trial memory retrieval test. The results showed that rats receiving pretest propofol（25 mg/kg） spent significantly less time in the target quadrant but showed no change in locomotor activity compared with those in the control group. Memory retrieval was accompanied by reduced phosphorylation of the serine-9 residue of GSK-3β in the hippocampus, whereas phosphorylation of the tyrosine-216 residue was unaffected. However, propofol blocked this retrieval-associated serine-9 phosphorylation. These findings suggest that subhypnotic propofol administration impairs memory retrieval and that the amnestic effects of propofol may be mediated by attenuated GSK-3β signaling in the hippocampus.
基金supported by the National Natural Science Foundation of China(T2394531)the National Key R&D Program of China(2024YFF1206500)+1 种基金the Shanghai Municipal Science and Technology Major Project(2018SHZDZX01)ZJ Lab,and the Shanghai Center for Brain Science and Brain-Inspired Technology,China.
文摘DDeeaarr EEddiittoorr,,The encoding and retrieval of emotional memories demands intricate interplay within the limbic network,where the network state is subject to significant reconfiguration by learning-induced plasticity,behavioral state,and contextual information[1].
基金supported by the National Natural Science Foundation of China (31721002, 81920208014, 31930051, 81800133)China Postdoctoral Science Foundation Funded Project (2018M642853)。
文摘The raphe nucleus is critical for feeding, rewarding and memory. However, how the heterogenous raphe neurons are molecularly and structurally organized to engage their divergent functions remains unknown. Here, we genetically target a subset of neurons expressing VGLUT3. VGLUT3 neurons control the efficacy of spatial memory retrieval by synapsing directly with parvalbumin-expressing GABA interneurons(PGIs) in the dentate gyrus. In a mouse model of Alzheimer's disease(AD mice),VGLUT3→PGIs synaptic transmission is impaired by ETV4 inhibition of VGLUT3 transcription. ETV4 binds to a promoter region of VGLUT3 and activates VGLUT3 transcription in VGLUT3 neurons. Strengthening VGLUT3→PGIs synaptic transmission by ETV4 activation of VGLUT3 transcription upscales the efficacy of spatial memory retrieval in AD mice. This study reports a novel circuit and molecular mechanism underlying the efficacy of spatial memory retrieval via ETV4 inhibition of VGLUT3 transcription and hence provides a promising target for therapeutic intervention of the disease progression.
基金the National Basic Research Program(973 Program)(Nos.2006CB500806 and 2009CB941301)。
文摘The mushroom body(MB),a bilateral brain structure pos-sessing about 2000-2500 neurons per hemisphere,plays a central role in olfactory learning and memory in Dros-ophila melanogaster.Extensive studies have demonstrat-ed that three major types of MB neurons(α/β,α’/β’andγ)exhibit distinct functions in memory processing,including the critical role of approximately 1000 MBα/βneurons in retrieving long-term memory.Inspired by recent fi ndings that MBα/βneurons can be further divided into three subdivisions(surface,posterior and core)and wherein theα/βcore neurons play an permissive role in long-term memory consolidation,we examined the functional differ-ences of all the three morphological subdivisions of MBα/βby temporally precise manipulation of their synaptic outputs during long-term memory retrieval.We found the normal neurotransmission from a combination of MBα/βsurface and posterior neurons is necessary for retrieving both aversive and appetitive long-term memory,whereas output from MBα/βposterior or core subdivision alone is dispensable.These results imply a specifi c requirement of about 500 MBα/βneurons in supporting long-term memory retrieval and a further functional partitioning for memory processing within the MBα/βregion.
基金supported in part by NIH NS059622,NS073636,DOD CDMRP W81XWH-12-1-0562,Merit Review Award I01 BX002356 from the U.SDepartment of Veterans Affairs,Craig H Neilsen Foundation 296749+1 种基金Indiana Spinal Cord and Brain Injury Research Foundation(ISCBIRF)019919Mari Hulman George Endowment Funds
文摘Neural degeneration and regeneration are important topics in neurological diseases. There are limited options for therapeutic interventions in neurological diseases that provide simultaneous spatial and temporal control of neurons. This drawback increases side effects due to non-specific targeting. Optogenetics is a technology that allows precise spatial and temporal control of cells. Therefore, this technique has high potential as a therapeutic strategy for neurological diseases. Even though the application of optogenetics in understanding brain functional organization and complex behaviour states have been elaborated, reviews of its therapeutic potential especially in neurodegeneration and regeneration are still limited. This short review presents representative work in optogenetics in disease models such as spinal cord injury, multiple sclerosis, epilepsy, Alzheimer＇s disease and Parkinson＇s disease. It is aimed to provide a broader perspective on optogenetic therapeutic potential in neurodegeneration and neural regeneration.
基金supported by the Innovation Group Project of Sichuan Province(20CXTD0090)the Fundamental Research Funds for the Central Universities(ZYGX2019Z018)+4 种基金the University of Electronic Science and Technology of China(UESTC)Shared Research Facilities of Electromagnetic Wave and Matter Interaction(Y0301901290100201)the National Natural Science Foundation of China(62004025)the International Postdoctoral Exchange Fellowship Program(Talent-Introduction Program,244125)the UESTC 100-Talent Project FundChina Postdoctoral Science Foundation(244125)。
文摘Artificial photonic synapses have set off a new upsurge for mimicking a series of neural activities in recent years.In particular,the investigation of learning and memory behaviors with pressure or emotion and corresponding mechanisms is currently the focus of more attention.Herein,a hippocampus-inspired device based on MoS_(2)for illumination time encoding is fabricated,in which the encryption technology is employed for data security.In addition,the pressureinduced memory behaviors with full memory function(memory trace)over time such as encoding,storage and retrieval are demonstrated,resulting from the decreasing positive photocurrent of the MoS;devices.The proposed mechanism of the memory effect when exposed to the light is elucidated in detail.Moreover,the effect of stress hormone on memory behavior is displayed via different illumination time periods and light intensities.These results indicate the potential application of MoS_(2)devices in artificial neural network.
