Memory deficit,which is often associated with aging and many psychiatric,neurological,and neurodegenerative diseases,has been a challenging issue for treatment.Up till now,all potential drug candidates have failed to ...Memory deficit,which is often associated with aging and many psychiatric,neurological,and neurodegenerative diseases,has been a challenging issue for treatment.Up till now,all potential drug candidates have failed to produce satisfa ctory effects.Therefore,in the search for a solution,we found that a treatment with the gene corresponding to the RGS14414protein in visual area V2,a brain area connected with brain circuits of the ventral stream and the medial temporal lobe,which is crucial for object recognition memory(ORM),can induce enhancement of ORM.In this study,we demonstrated that the same treatment with RGS14414in visual area V2,which is relatively unaffected in neurodegenerative diseases such as Alzheimer s disease,produced longlasting enhancement of ORM in young animals and prevent ORM deficits in rodent models of aging and Alzheimer’s disease.Furthermore,we found that the prevention of memory deficits was mediated through the upregulation of neuronal arbo rization and spine density,as well as an increase in brain-derived neurotrophic factor(BDNF).A knockdown of BDNF gene in RGS14414-treated aging rats and Alzheimer s disease model mice caused complete loss in the upregulation of neuronal structural plasticity and in the prevention of ORM deficits.These findings suggest that BDNF-mediated neuronal structural plasticity in area V2 is crucial in the prevention of memory deficits in RGS14414-treated rodent models of aging and Alzheimer’s disease.Therefore,our findings of RGS14414gene-mediated activation of neuronal circuits in visual area V2 have therapeutic relevance in the treatment of memory deficits.展开更多
Objective We aimed to investigate whether antagonism of the cannabinoid CB1 receptor(CB1R)could affect novel object recognition(NOR)memory in chronically rapid eye movement sleep-deprived(RSD)rats.Methods The animals ...Objective We aimed to investigate whether antagonism of the cannabinoid CB1 receptor(CB1R)could affect novel object recognition(NOR)memory in chronically rapid eye movement sleep-deprived(RSD)rats.Methods The animals were examined for recognition memory following a 7-day chronic partial RSD paradigm using the multiple platform technique.The CB1R antagonist rimonabant(1 or 3 mg/kg,i.p.)was administered either at one hour prior to the sample phase for acquisition,or immediately after the sample phase for consolidation,or at one hour before the test phase for retrieval of NOR memory.For the reconsolidation task,rimonabant was administered immediately after the second sample phase.Results The RSD episode impaired acquisition,consolidation,and retrieval,but it did not affect the reconsolidation of NOR memory.Rimonabant administration did not affect acquisition,consolidation,and reconsolidation;however,it attenuated impairment of the retrieval of NOR memory induced by chronic RSD.Conclusions These findings,along with our previous report,would seem to suggest that RSD may affect different phases of recognition memory based on its duration.Importantly,it seems that the CB1R may,at least in part,be involved in the adverse effects of chronic RSD on the retrieval,but not in the acquisition,consolidation,and reconsolidation,of NOR memory.展开更多
Melatonin (MEL) has been reported to have acute enhancing effects on some aspects of cognition. Recently, we revealed that N1-acetyl-5-methoxyquinuramine (AMK), a brain metabolite of MEL, is much more potent than MEL ...Melatonin (MEL) has been reported to have acute enhancing effects on some aspects of cognition. Recently, we revealed that N1-acetyl-5-methoxyquinuramine (AMK), a brain metabolite of MEL, is much more potent than MEL in converting short-term memory (STM) to long-term memory (LTM) with a single administration immediately after the acquisition trial of the novel object recognition (NOR) task. These data suggest that the memory-enhancing effects of MEL may be mediated by mechanisms independent of the activation of MEL MT1 and MT2 receptors. In the present study, we examined the contribution of MT1 and MT2 receptor-mediated and non-receptor-mediated mechanisms to the acute memory-enhancing effects of MEL using NOR task. Mice were administered with either MEL, AMK, or a highly selective MT1/MT2 receptor agonist ramelteon (RAM) immediately after the acquisition trial and the effects of varying doses of these drugs on both STM and LTM performance were compared. We found that both AMK and RAM were more potent than MEL in both facilitating STM and promoting LTM formation. We also found that pretreatment with luzindole, a MT1/MT2 receptor antagonist, markedly suppressed only the effects of RAM. These results suggest that acutely administered MEL enhances NOR memory through both MT1 and MT2 receptor-mediated and non-receptor-mediated mechanisms.展开更多
Optogenetics is a combination of optics and genetics technology that can be used to activate or inhibit specific cells in tissues. It has been used to treat Parkinson’s disease, epilepsy and neurological diseases, bu...Optogenetics is a combination of optics and genetics technology that can be used to activate or inhibit specific cells in tissues. It has been used to treat Parkinson’s disease, epilepsy and neurological diseases, but rarely Alzheimer’s disease. Adeno-associated virus carrying the CaMK promoter driving the optogenetic channelrhodopsin-2 (CHR2) gene (or without the CHR2 gene, as control) was injected into the bilateral dentate gyri, followed by repeated intrahippocampal injections of soluble low-molecular-weight amyloid-β1–42 peptide (Aβ1–42). Subsequently, the region was stimulated with a 473 nm laser (1–3 ms, 10 Hz, 5 minutes). The novel object recognition test was conducted to test memory function in mice. Immunohistochemical staining was performed to analyze the numbers of NeuN and synapsin Ia/b-positive cells in the hippocampus. Western blot assay was carried out to analyze the expression levels of glial fibrillary acidic protein, NeuN, synapsin Ia/b, metabotropic glutamate receptor-1a (mGluR-1a), mGluR-5, N-methyl-D-aspartate receptor subunit NR1, glutamate receptor 2, interleukin-1β, interleukin-6 and interleukin-10. Optogenetic stimulation improved working and short-term memory in mice with Alzheimer’s disease. This neuroprotective effect was associated with increased expression of NR1, glutamate receptor 2 and mGluR-5 in the hippocampus, and decreased expression of glial fibrillary acidic protein and interleukin-6. Our results show that optogenetics can be used to regulate the neuronal-glial network to ameliorate memory functions in mice with Alzheimer’s disease. The study was approved by the Animal Resources Committee of Jinan University, China (approval No. LL-KT-2011134) on February 28, 2011.展开更多
In dense pedestrian tracking,frequent object occlusions and close distances between objects cause difficulty when accurately estimating object trajectories.In this study,a conditional random field tracking model is es...In dense pedestrian tracking,frequent object occlusions and close distances between objects cause difficulty when accurately estimating object trajectories.In this study,a conditional random field tracking model is established by using a visual long short term memory network in the three-dimensional(3D)space and the motion estimations jointly performed on object trajectory segments.Object visual field information is added to the long short term memory network to improve the accuracy of the motion related object pair selection and motion estimation.To address the uncertainty of the length and interval of trajectory segments,a multimode long short term memory network is proposed for the object motion estimation.The tracking performance is evaluated using the PETS2009 dataset.The experimental results show that the proposed method achieves better performance than the tracking methods based on the independent motion estimation.展开更多
The current study investigated whether domestic dogs encode local and/or global cues in spatial working memory. Seven dogs were trained to use a source of allocentric information (local and/or global cues) to locate a...The current study investigated whether domestic dogs encode local and/or global cues in spatial working memory. Seven dogs were trained to use a source of allocentric information (local and/or global cues) to locate an attractive object they saw move and disappear behind one of the three opaque boxes arrayed in front of them. To do so, after the disappearance of the target object and out of the dogs’ knowledge, all sources of allocentric information were simultaneously shifted to a new spatial position and the dogs were forced to follow a U-shaped pathway leading to the hiding box. Out of the seven dogs that were trained in the detour problem, only three dogs learned to use the cues that were moved from trial to trial. On tests, local (boxes and experimenter) and/or global cues (walls of the room) were systematically and drastically shifted to a new position in the testing chamber. Although they easily succeeded the control trials, the three dogs failed to use a specific source of allocentric information when local and global cues were put in conflict. In discussion, we explore several hypotheses to explain why dogs have difficulties to use allocentric cues to locate a hidden object in a detour problem and why they do not differentiate the local and global cues in this particular experimental setting.展开更多
This study investigated episodic memory in prodromal HD. Three groups were compared (N = 70): mutation carriers with less than 12.5 years to disease onset (n = 16), mutation carriers with 12.5 or more years to disease...This study investigated episodic memory in prodromal HD. Three groups were compared (N = 70): mutation carriers with less than 12.5 years to disease onset (n = 16), mutation carriers with 12.5 or more years to disease onset (n = 16), and noncarriers (n = 38). Episodic memory was assessed using the Fuld Object Memory Evaluation, which included multimodal presentation and selective reminding, and the Claeson-Dahl Learning Test which included verbal repeated presentation and recall trials. Both carrier groups demonstrated deficient episodic memory compared to noncarriers. The results suggest deficient episodic memory in prodromal HD, and that inconsistent retrieval contributes to these deficits. Multimodal presentation attenuates the deficits.展开更多
Critics have observed that memory is an important theme in Lu Xun's writings. At the same time, memory--more precisely a struggle over the shaping of cultural memory--is a vital component of the iconoclastic May Four...Critics have observed that memory is an important theme in Lu Xun's writings. At the same time, memory--more precisely a struggle over the shaping of cultural memory--is a vital component of the iconoclastic May Fourth Movement with which Lu Xun is strongly associated. This article examines the ways in which several of Lu Xun's creative writings and memoirs depict memory and its transmission. I argue that, 1) These texts suggest the importance of objects as mnemonic devices that aid the transmission of memory, 2) The agency of the receiver is key in interpreting these texts and in transmitting them onward, and 3) That Lu Xun posits the texts he creates as such mnemonic objects that serve to transmit his interpretation of cultural and personal memory to his readers. Lu Xun's texts thus implicate the reader in the author's project of transmitting onward his reinterpretation of the past in the hope of redeeming China. Examining these mechanisms of memory transmission I conclude that for Lu Xun redemption lies not in a transcendent future but in reexamining the past.展开更多
Age-related memory impairments show a progressive decline across lifespan. Studies have demonstrated equivocal results in biological and behavioral outcomes of aging. Thus, in the present study we examined the novel o...Age-related memory impairments show a progressive decline across lifespan. Studies have demonstrated equivocal results in biological and behavioral outcomes of aging. Thus, in the present study we examined the novel object recognition task at a delay period that has been shown to be impaired in aged rats of two different strains. Moreover, we used a strain of rats, Fisher 344XBrown Norway, which have published age-related biological changes in the brain. Young (10 month old) and aged (28 month old) rats were tested on a standard novel object recognition task with a 50-minute delay period. The data showed that young and aged rats in the strain we used performed equally well on the novel object recognition task and that both young and old rats demonstrated a righthanded side preference for the novel object. Our data suggested that novel object recognition is not impaired in aged rats although both young and old rats have a demonstrated side preference. Thus, it may be that genetic differences across strains contribute to the equivocal results in behavior, and genetic variance likely influences the course of cognitive aging.展开更多
Visual impairment is one of the major problems among people of all age groups across the globe.Visually Impaired Persons(VIPs)require help from others to carry out their day-to-day tasks.Since they experience several ...Visual impairment is one of the major problems among people of all age groups across the globe.Visually Impaired Persons(VIPs)require help from others to carry out their day-to-day tasks.Since they experience several problems in their daily lives,technical intervention can help them resolve the challenges.In this background,an automatic object detection tool is the need of the hour to empower VIPs with safe navigation.The recent advances in the Internet of Things(IoT)and Deep Learning(DL)techniques make it possible.The current study proposes IoT-assisted Transient Search Optimization with a Lightweight RetinaNetbased object detection(TSOLWR-ODVIP)model to help VIPs.The primary aim of the presented TSOLWR-ODVIP technique is to identify different objects surrounding VIPs and to convey the information via audio message to them.For data acquisition,IoT devices are used in this study.Then,the Lightweight RetinaNet(LWR)model is applied to detect objects accurately.Next,the TSO algorithm is employed for fine-tuning the hyperparameters involved in the LWR model.Finally,the Long Short-Term Memory(LSTM)model is exploited for classifying objects.The performance of the proposed TSOLWR-ODVIP technique was evaluated using a set of objects,and the results were examined under distinct aspects.The comparison study outcomes confirmed that the TSOLWR-ODVIP model could effectually detect and classify the objects,enhancing the quality of life of VIPs.展开更多
基金supported by grants from the Ministerio de Economia y Competitividad(BFU2013-43458-R)Junta de Andalucia(P12-CTS-1694 and Proyexcel-00422)to ZUK。
文摘Memory deficit,which is often associated with aging and many psychiatric,neurological,and neurodegenerative diseases,has been a challenging issue for treatment.Up till now,all potential drug candidates have failed to produce satisfa ctory effects.Therefore,in the search for a solution,we found that a treatment with the gene corresponding to the RGS14414protein in visual area V2,a brain area connected with brain circuits of the ventral stream and the medial temporal lobe,which is crucial for object recognition memory(ORM),can induce enhancement of ORM.In this study,we demonstrated that the same treatment with RGS14414in visual area V2,which is relatively unaffected in neurodegenerative diseases such as Alzheimer s disease,produced longlasting enhancement of ORM in young animals and prevent ORM deficits in rodent models of aging and Alzheimer’s disease.Furthermore,we found that the prevention of memory deficits was mediated through the upregulation of neuronal arbo rization and spine density,as well as an increase in brain-derived neurotrophic factor(BDNF).A knockdown of BDNF gene in RGS14414-treated aging rats and Alzheimer s disease model mice caused complete loss in the upregulation of neuronal structural plasticity and in the prevention of ORM deficits.These findings suggest that BDNF-mediated neuronal structural plasticity in area V2 is crucial in the prevention of memory deficits in RGS14414-treated rodent models of aging and Alzheimer’s disease.Therefore,our findings of RGS14414gene-mediated activation of neuronal circuits in visual area V2 have therapeutic relevance in the treatment of memory deficits.
基金Supported by the Research Council of Kermanshah University of Medical Sciences,Kermanshah,Iran for financial support(grant no.:990812).
文摘Objective We aimed to investigate whether antagonism of the cannabinoid CB1 receptor(CB1R)could affect novel object recognition(NOR)memory in chronically rapid eye movement sleep-deprived(RSD)rats.Methods The animals were examined for recognition memory following a 7-day chronic partial RSD paradigm using the multiple platform technique.The CB1R antagonist rimonabant(1 or 3 mg/kg,i.p.)was administered either at one hour prior to the sample phase for acquisition,or immediately after the sample phase for consolidation,or at one hour before the test phase for retrieval of NOR memory.For the reconsolidation task,rimonabant was administered immediately after the second sample phase.Results The RSD episode impaired acquisition,consolidation,and retrieval,but it did not affect the reconsolidation of NOR memory.Rimonabant administration did not affect acquisition,consolidation,and reconsolidation;however,it attenuated impairment of the retrieval of NOR memory induced by chronic RSD.Conclusions These findings,along with our previous report,would seem to suggest that RSD may affect different phases of recognition memory based on its duration.Importantly,it seems that the CB1R may,at least in part,be involved in the adverse effects of chronic RSD on the retrieval,but not in the acquisition,consolidation,and reconsolidation,of NOR memory.
文摘Melatonin (MEL) has been reported to have acute enhancing effects on some aspects of cognition. Recently, we revealed that N1-acetyl-5-methoxyquinuramine (AMK), a brain metabolite of MEL, is much more potent than MEL in converting short-term memory (STM) to long-term memory (LTM) with a single administration immediately after the acquisition trial of the novel object recognition (NOR) task. These data suggest that the memory-enhancing effects of MEL may be mediated by mechanisms independent of the activation of MEL MT1 and MT2 receptors. In the present study, we examined the contribution of MT1 and MT2 receptor-mediated and non-receptor-mediated mechanisms to the acute memory-enhancing effects of MEL using NOR task. Mice were administered with either MEL, AMK, or a highly selective MT1/MT2 receptor agonist ramelteon (RAM) immediately after the acquisition trial and the effects of varying doses of these drugs on both STM and LTM performance were compared. We found that both AMK and RAM were more potent than MEL in both facilitating STM and promoting LTM formation. We also found that pretreatment with luzindole, a MT1/MT2 receptor antagonist, markedly suppressed only the effects of RAM. These results suggest that acutely administered MEL enhances NOR memory through both MT1 and MT2 receptor-mediated and non-receptor-mediated mechanisms.
基金supported by the National Natural Science Foundation of China,No.81171191(to LYZ)the Shenzhen Special Fund Project on Strategic Emerging Industry Development of China,No.JCYJ20160422170522075(to LYZ)the Shenzhen Healthcare Research Project of China,No.201601015(to LYZ)
文摘Optogenetics is a combination of optics and genetics technology that can be used to activate or inhibit specific cells in tissues. It has been used to treat Parkinson’s disease, epilepsy and neurological diseases, but rarely Alzheimer’s disease. Adeno-associated virus carrying the CaMK promoter driving the optogenetic channelrhodopsin-2 (CHR2) gene (or without the CHR2 gene, as control) was injected into the bilateral dentate gyri, followed by repeated intrahippocampal injections of soluble low-molecular-weight amyloid-β1–42 peptide (Aβ1–42). Subsequently, the region was stimulated with a 473 nm laser (1–3 ms, 10 Hz, 5 minutes). The novel object recognition test was conducted to test memory function in mice. Immunohistochemical staining was performed to analyze the numbers of NeuN and synapsin Ia/b-positive cells in the hippocampus. Western blot assay was carried out to analyze the expression levels of glial fibrillary acidic protein, NeuN, synapsin Ia/b, metabotropic glutamate receptor-1a (mGluR-1a), mGluR-5, N-methyl-D-aspartate receptor subunit NR1, glutamate receptor 2, interleukin-1β, interleukin-6 and interleukin-10. Optogenetic stimulation improved working and short-term memory in mice with Alzheimer’s disease. This neuroprotective effect was associated with increased expression of NR1, glutamate receptor 2 and mGluR-5 in the hippocampus, and decreased expression of glial fibrillary acidic protein and interleukin-6. Our results show that optogenetics can be used to regulate the neuronal-glial network to ameliorate memory functions in mice with Alzheimer’s disease. The study was approved by the Animal Resources Committee of Jinan University, China (approval No. LL-KT-2011134) on February 28, 2011.
文摘In dense pedestrian tracking,frequent object occlusions and close distances between objects cause difficulty when accurately estimating object trajectories.In this study,a conditional random field tracking model is established by using a visual long short term memory network in the three-dimensional(3D)space and the motion estimations jointly performed on object trajectory segments.Object visual field information is added to the long short term memory network to improve the accuracy of the motion related object pair selection and motion estimation.To address the uncertainty of the length and interval of trajectory segments,a multimode long short term memory network is proposed for the object motion estimation.The tracking performance is evaluated using the PETS2009 dataset.The experimental results show that the proposed method achieves better performance than the tracking methods based on the independent motion estimation.
文摘The current study investigated whether domestic dogs encode local and/or global cues in spatial working memory. Seven dogs were trained to use a source of allocentric information (local and/or global cues) to locate an attractive object they saw move and disappear behind one of the three opaque boxes arrayed in front of them. To do so, after the disappearance of the target object and out of the dogs’ knowledge, all sources of allocentric information were simultaneously shifted to a new spatial position and the dogs were forced to follow a U-shaped pathway leading to the hiding box. Out of the seven dogs that were trained in the detour problem, only three dogs learned to use the cues that were moved from trial to trial. On tests, local (boxes and experimenter) and/or global cues (walls of the room) were systematically and drastically shifted to a new position in the testing chamber. Although they easily succeeded the control trials, the three dogs failed to use a specific source of allocentric information when local and global cues were put in conflict. In discussion, we explore several hypotheses to explain why dogs have difficulties to use allocentric cues to locate a hidden object in a detour problem and why they do not differentiate the local and global cues in this particular experimental setting.
基金Department of Clinical Genetics, Karolinska University Hospital
文摘This study investigated episodic memory in prodromal HD. Three groups were compared (N = 70): mutation carriers with less than 12.5 years to disease onset (n = 16), mutation carriers with 12.5 or more years to disease onset (n = 16), and noncarriers (n = 38). Episodic memory was assessed using the Fuld Object Memory Evaluation, which included multimodal presentation and selective reminding, and the Claeson-Dahl Learning Test which included verbal repeated presentation and recall trials. Both carrier groups demonstrated deficient episodic memory compared to noncarriers. The results suggest deficient episodic memory in prodromal HD, and that inconsistent retrieval contributes to these deficits. Multimodal presentation attenuates the deficits.
文摘Critics have observed that memory is an important theme in Lu Xun's writings. At the same time, memory--more precisely a struggle over the shaping of cultural memory--is a vital component of the iconoclastic May Fourth Movement with which Lu Xun is strongly associated. This article examines the ways in which several of Lu Xun's creative writings and memoirs depict memory and its transmission. I argue that, 1) These texts suggest the importance of objects as mnemonic devices that aid the transmission of memory, 2) The agency of the receiver is key in interpreting these texts and in transmitting them onward, and 3) That Lu Xun posits the texts he creates as such mnemonic objects that serve to transmit his interpretation of cultural and personal memory to his readers. Lu Xun's texts thus implicate the reader in the author's project of transmitting onward his reinterpretation of the past in the hope of redeeming China. Examining these mechanisms of memory transmission I conclude that for Lu Xun redemption lies not in a transcendent future but in reexamining the past.
文摘Age-related memory impairments show a progressive decline across lifespan. Studies have demonstrated equivocal results in biological and behavioral outcomes of aging. Thus, in the present study we examined the novel object recognition task at a delay period that has been shown to be impaired in aged rats of two different strains. Moreover, we used a strain of rats, Fisher 344XBrown Norway, which have published age-related biological changes in the brain. Young (10 month old) and aged (28 month old) rats were tested on a standard novel object recognition task with a 50-minute delay period. The data showed that young and aged rats in the strain we used performed equally well on the novel object recognition task and that both young and old rats demonstrated a righthanded side preference for the novel object. Our data suggested that novel object recognition is not impaired in aged rats although both young and old rats have a demonstrated side preference. Thus, it may be that genetic differences across strains contribute to the equivocal results in behavior, and genetic variance likely influences the course of cognitive aging.
基金The authors extend their appreciation to the King Salman center for Disability Research for funding this work through Research Group no KSRG-2022-030。
文摘Visual impairment is one of the major problems among people of all age groups across the globe.Visually Impaired Persons(VIPs)require help from others to carry out their day-to-day tasks.Since they experience several problems in their daily lives,technical intervention can help them resolve the challenges.In this background,an automatic object detection tool is the need of the hour to empower VIPs with safe navigation.The recent advances in the Internet of Things(IoT)and Deep Learning(DL)techniques make it possible.The current study proposes IoT-assisted Transient Search Optimization with a Lightweight RetinaNetbased object detection(TSOLWR-ODVIP)model to help VIPs.The primary aim of the presented TSOLWR-ODVIP technique is to identify different objects surrounding VIPs and to convey the information via audio message to them.For data acquisition,IoT devices are used in this study.Then,the Lightweight RetinaNet(LWR)model is applied to detect objects accurately.Next,the TSO algorithm is employed for fine-tuning the hyperparameters involved in the LWR model.Finally,the Long Short-Term Memory(LSTM)model is exploited for classifying objects.The performance of the proposed TSOLWR-ODVIP technique was evaluated using a set of objects,and the results were examined under distinct aspects.The comparison study outcomes confirmed that the TSOLWR-ODVIP model could effectually detect and classify the objects,enhancing the quality of life of VIPs.