The visual cortex is an essential part of the brain for processing visual information.It exhibits structural and functional plasticity,which is crucial for adapting to complex visual environments.The quintessential ma...The visual cortex is an essential part of the brain for processing visual information.It exhibits structural and functional plasticity,which is crucial for adapting to complex visual environments.The quintessential manifestation of visual cortical plasticity is ocular dominance plasticity during the critical period,which involves numerous cellular and molecular events.While previous studies have emphasized the role of visual cortical neurons and their associated functional molecules in visual plasticity,recent findings have revealed that structural factors such as the extracellular matrix and glia are also involved.Investigating how these molecules interact to form a complex network that facilitates plasticity in the visual cortex is crucial to our understanding of the development of the visual system and the advancement of therapeutic strategies for visual disorders like amblyopia.展开更多
Nogo-A and Nogo receptor （NgR） expression in the visual cortex following a critical developmental period （postnatal days 20-60） has been previously shown. However, little is known regarding Nogo-A and NgR expressi...Nogo-A and Nogo receptor （NgR） expression in the visual cortex following a critical developmental period （postnatal days 20-60） has been previously shown. However, little is known regarding Nogo-A and NgR expression between postnatal day 0 and initiation of the critical period. The present study analyzed Nogo-A and NgR expression at four different time points： postnatal day 0 （P0）, before critical period （P14）, during critical period （P28）, and after critical period （P60）. Results showed significantly increased Nogo-A mRNA and protein expression levels in the visual cortex following birth, and expression levels remained steady between P28 and P60. NgR mRNA or protein expression was dramatically upregulated with age and peaked at P14 or P28, respectively, and maintained high expression to P60. In addition, Nogo-A and NgR expression was analyzed in each visual cortex layer in normal developing rats and rats with monocular deprivation. Monocular deprivation decreased Nogo-A and NgR mRNA and protein expression in the rat visual cortex, in particular in layers Ⅱ-Ⅲ and Ⅳ in the visual cortex contralateral to the deprived eye. These findings suggested that Nogo-A and NgR regulated termination of the critical period in experience- dependent visual cortical plasticity.展开更多
Critical periods(CPs)are defined as postnatal developmental windows during which brain circuits exhibit heightened sensitivity to altered experiences or sensory inputs,particularly during brain development in humans a...Critical periods(CPs)are defined as postnatal developmental windows during which brain circuits exhibit heightened sensitivity to altered experiences or sensory inputs,particularly during brain development in humans and animals.During the CP,experience-induced refinements of neural connections are crucial for establishing adaptive and mature brain functions,and aberrant CPs are often accompanied by many neurodevelopmental disorders(NDDs),including autism spectrum disorders and schizophrenia.Understanding neural mechanisms underlying the CP regulation is key to delineating the etiology of NDDs caused by abnormal postnatal neurodevelopment.Recent evidence from studies using innovative experimental tools has continuously revisited the inhibition-gating theory of CP to systematically elucidate the differential roles of distinct inhibitory circuits.Here,we provide a comprehensive review of classical experimental findings and emerging inhibitory-circuit regulation mechanisms of the CP,and further discuss how aberrant CP plasticity is associated with NDDs.展开更多
Purpose: To study the property of LTP in layers Ⅱ～Ⅳof the rats visual cortex at different postnatal days induced by pairing low-frequency stimulation at layer Ⅳ with post synaptic depolarization in order to explor...Purpose: To study the property of LTP in layers Ⅱ～Ⅳof the rats visual cortex at different postnatal days induced by pairing low-frequency stimulation at layer Ⅳ with post synaptic depolarization in order to explore the synaptic and cellular mechanism of experience-dependent plasticity in the visual cortex.Methods: Postsynaptic currents (PSCs) of layers Ⅱ～Ⅳ in visual cortex slices of Wistar rats aged P0-29 d were recorded by patch-clamp whole cell recording method. Long-term potentiation (LTP) was induced by low-frequency stimulation (LFS) at 1Hz for 60～90 s.Each pulse of the LFS paired with depolarization of post-synaptic neurons to -20 mV.100μM APV, a kind of competitive N-methyl-d-aspartate (NMDA) receptor antagonist, was both applied to some slices to test the property of LTP.Results: 1. The LTP incidence was very low before P10d (5/34), and increased rapidly to the top at P15-24 d (17/28), then decreased sharply to 1/5 at P25-29 d, coinciding well with the critical period of plasticity of rat visual cortex. The LTP incidence of P15-29d (after eye opening, 18/33) was significantly higher than that of P0-14 d (before eye opening, 12/43, P ＜ 0.05). 2. Compared with non-APV applied group (30/76), LTP incidence of APV applied group (4/33) was significantly decreased (P ＜ 0.01 ). There were 4 Ⅳ-Ⅳ horizontal synapses. APV application could not block the LTP induction.Conclusions: 1. LTP was a reflection of naturally occurring, experience-dependent plasticity in rat visual cortex. The patterned visual stimuli received after eye opening might be an activation factor of the synaptic plasticity. 2. LTP of visual cortex induced by LFS in layer Ⅳ paired with postsynaptic depolarization was NMDA receptor dependent during the critical period of visual plasticity. However, there were LTP existed in Ⅳ-Ⅳ horizontal synapses which could not be blocked by 100μM APV.展开更多
Synaptic plasticity is essential for maintaining neuronal function in the central nervous system and serves as a critical indicator of the effects of neurodegenerative disease.Glaucoma directly impairs retinal ganglio...Synaptic plasticity is essential for maintaining neuronal function in the central nervous system and serves as a critical indicator of the effects of neurodegenerative disease.Glaucoma directly impairs retinal ganglion cells and their axons,leading to axonal transport dysfuntion,subsequently causing secondary damage to anterior or posterior ends of the visual system.Accordingly,recent evidence indicates that glaucoma is a degenerative disease of the central nervous system that causes damage throughout the visual pathway.However,the effects of glaucoma on synaptic plasticity in the primary visual cortex remain unclear.In this study,we established a mouse model of unilateral chronic ocular hypertension by injecting magnetic microbeads into the anterior chamber of one eye.We found that,after 4 weeks of chronic ocular hypertension,the neuronal somas were smaller in the superior colliculus and lateral geniculate body regions of the brain contralateral to the affected eye.This was accompanied by glial cell activation and increased expression of inflammatory factors.After 8 weeks of ocular hypertension,we observed a reduction in the number of excitatory and inhibitory synapses,dendritic spines,and activation of glial cells in the primary visual cortex contralateral to the affected eye.These findings suggest that glaucoma not only directly damages the retina but also induces alterations in synapses and dendritic spines in the primary visual cortex,providing new insights into the pathogenesis of glaucoma.展开更多
Microglia are the resident macrophages of the central nervous system.Microglia possess varied morphologies and functions.Under normal physiological conditions,microglia mainly exist in a resting state and constantly m...Microglia are the resident macrophages of the central nervous system.Microglia possess varied morphologies and functions.Under normal physiological conditions,microglia mainly exist in a resting state and constantly monitor their microenvironment and survey neuronal and synaptic activity.Through the C1 q,C3 and CR3"Eat Me"and CD47 and SIRPα"Don't Eat Me"complement pathways,as well as other pathways such as CX3 CR1 signaling,resting microglia regulate synaptic pruning,a process crucial for the promotion of synapse formation and the regulation of neuronal activity and synaptic plasticity.By mediating synaptic pruning,resting microglia play an important role in the regulation of experience-dependent plasticity in the barrel cortex and visual cortex after whisker removal or monocular deprivation,and also in the regulation of learning and memory,including the modulation of memory strength,forgetfulness,and memory quality.As a response to brain injury,infection or neuroinflammation,microglia become activated and increase in number.Activated microglia change to an amoeboid shape,migrate to sites of inflammation and secrete proteins such as cytokines,chemokines and reactive oxygen species.These molecules released by microglia can lead to synaptic plasticity and learning and memory deficits associated with aging,Alzheimer's disease,traumatic brain injury,HIV-associated neurocognitive disorder,and other neurological or mental disorders such as autism,depression and post-traumatic stress disorder.With a focus mainly on recently published literature,here we reviewed the studies investigating the role of resting microglia in synaptic plasticity and learning and memory,as well as how activated microglia modulate disease-related plasticity and learning and memory deficits.By summarizing the function of microglia in these processes,we aim to provide an overview of microglia regulation of synaptic plasticity and learning and memory,and to discuss the possibility of microglia manipulation as a therapeutic to ameliorate cognitive deficits associated with aging,Alzheimer's disease,traumatic brain injury,HIV-associated neurocognitive disorder,and mental disorders.展开更多
AIM:To investigate the postnatal development of parvalbumin(PV)-positive gamma-aminobutyric acid(GABA)interneurons and the co-expression of perineuronal nets(PNNs)and PV in the visual cortex of rats,as well as the reg...AIM:To investigate the postnatal development of parvalbumin(PV)-positive gamma-aminobutyric acid(GABA)interneurons and the co-expression of perineuronal nets(PNNs)and PV in the visual cortex of rats,as well as the regulatory effects of fluoxetine(FLX)treatment and binocular form deprivation(BFD)on these indices.METHODS:Wistar rats were assigned to three experimental cohorts:1)Age-related groups:postnatal week(PW)1,PW3,PW5,PW7,and PW9;2)FLX treatment duration groups:FLX 0W,FLX 2W,FLX 4W,FLX 6W,and FLX 8W;3)Intervention groups:control(Cont),FLX,BFD,and BFD+FLX.The levels of PNNs,PV,and PNNs/PV coexpression in the visual cortex were detected and analyzed.RESULTS:The density of PV-positive cells and the coexpression of PNNs and PV increased gradually with the maturation of the visual cortex(b=0.960,P<0.01).The ratio of PV-positive cells surrounded by PNNs to total PV-positive cells(PNNs+/PV+/total PV+)was significantly decreased in the FLX 4W group(χ^(2)=9.03,P=0.003).There was no significant difference in the PNNs+/PV+/total PV+ratio between the FLX and BFD groups(χ^(2)=1.08,P=0.161),but a significant difference was observed between the BFD+FLX group and the BFD group(χ^(2)=5.82,P<0.01).CONCLUSION:The number of PV-positive neurons and PNNs-surrounded PV neurons in the rat visual cortex increases postnatally and reaches adult levels by postnatal week 7.Chronic FLX treatment downregulates these expressions.Combined 4-week FLX treatment and BFD exerts a more significant inhibitory effect on the PNNs+/PV+/total PV+ratio than either intervention alone.展开更多
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
Objective:To report a case of anisometropic amblyopia reversal as a result of branch retinal vein occlusion (BRVO) occurring in the sound fellow eye.Methods:An adult patient with childhood anisometropic amblyopia was ...Objective:To report a case of anisometropic amblyopia reversal as a result of branch retinal vein occlusion (BRVO) occurring in the sound fellow eye.Methods:An adult patient with childhood anisometropic amblyopia was found to exhibit gradually visual acuity improvement in the amblyopic eye as the result of decreased visual acuity in the sound fellow eye.Results:Four years after the BRVO,the patient subsequently regained normal vision in the previously amblyopic eye.Conclusion:Visual plasticity is preserved in adults but may require special or stronger stimulation and possibly longer treatment time than during childhood.展开更多
Background:Visual deficits,caused by ocular disease or trauma,can cause lasting damage.However,recent research has focused on neural plasticity as a means to regain visual functions.In order to better understand the i...Background:Visual deficits,caused by ocular disease or trauma,can cause lasting damage.However,recent research has focused on neural plasticity as a means to regain visual functions.In order to better understand the involvement of neural plasticity and reorganization in partial vision restoration,we aim to evaluate the partial recovery of a visual deficit over time using two behavioural tests.In our study,a partial optic nerve crush(pONC)serves as an induced visual deficit,allowing for residual vision from surviving cells.Methods:Visual functions in C57BL/6 mice was measured using two behavioural tests prior to a bilateral pONC,then at various time points after the pONC.In this study,two injury intensities were used:a high intensity pONC with the full force of self-closing forceps,and a low intensity pONC,in which a calibrated space was left between the forceps at the closed position.The two behavioural tests consisted of the optomotor reflex(OMR)and the visual cliff(VC)tests.The OMR test measures the mouse’s tracking reflex in response to moving sinusoidal gratings.The VC test,on the other hand,evaluates exploratory behaviour,by simulating a cliff to observe the animal’s sense of depth perception.After the behavioural evaluation,surviving retinal ganglion cells were counted.Results:The high intensity pONC resulted in a total loss of visual acuity as measured by the OMR test,with no improvement in the following 4 weeks.However,the light intensity pONC showed the same initial loss,but recovery was observed as of day 3,and results in 40-60%recovery after 4 weeks.With the VC test,mice with intact vision will avoid the deep end,opting to spend more time in the shallow end.However,after both high and low intensity pONCs,this preference is no longer observed.Both groups show a return to the shallow end preference at day 14,though the low intensity pONC group showed a stronger preference similar to baseline performance.The percentage of surviving retinal ganglion cells was higher with the low intensity(68%)than with the high intensity(17%)pONC.Conclusions:There is evidence of visual recovery at the behavioural level following a pONC,though very little recovery was observed following a high intensity pONC,and only with the VC test.Therefore,a certain amount of residual retinal input may be required for recovery at the behavioural level.展开更多
Amblyopia is a neurodevelopmental vision disorder resulting from abnormal visual input during the critical period of visual development,such as strabismus,uncorrected anisometropia,high refractive errors,and form depr...Amblyopia is a neurodevelopmental vision disorder resulting from abnormal visual input during the critical period of visual development,such as strabismus,uncorrected anisometropia,high refractive errors,and form deprivation.It is frequently associated with reduced visual acuity and deficits in binocular vision.Traditional occlusion therapy for amblyopia has typically been restricted to infants and young children during the critical period of visual development,as it is believed to be ineffective for older children and adults due to the decreased plasticity of the mature brain.Our research group has concentrated on pivotal scientific issues in amblyopia,including quantitative methods for detecting binocular vision,especially interocular visual suppression,the mechanisms underlying binocular vision impairment in amblyopia,treatment methods and their evaluations for amblyopia,and visual plasticity and its neural mechanisms in amblyopia.This paper summarizes the visual mechanisms and treatment modalities of amblyopia based on our research and both domestic and foreign sources,while also looking forward to the future development of this field in light of existing problems.展开更多
背景:相比于常规重复经颅磁刺激,Theta爆发式经颅磁刺激因具有刺激时间短、效率高、安全性好和效果持久等优势,正受到各领域学者的广泛关注,研究热度持续上升。目的:通过对近20年国际Theta爆发式经颅磁刺激研究进行文献计量学的可视化分...背景:相比于常规重复经颅磁刺激,Theta爆发式经颅磁刺激因具有刺激时间短、效率高、安全性好和效果持久等优势,正受到各领域学者的广泛关注,研究热度持续上升。目的:通过对近20年国际Theta爆发式经颅磁刺激研究进行文献计量学的可视化分析,梳理Theta爆发式经颅磁刺激研究的发展脉络,总结研究现状,揭示研究热点和发展趋势,为后续研究提供借鉴和参考。方法:检索Web of Science核心集数据库中2005年1月至2024年6月有关Theta爆发式经颅磁刺激的相关文献,应用CiteSpace软件进行年度发文量分析,国家、机构和作者合作共现分析,参考文献、期刊和作者共被引分析,关键词共现、聚类、时间演化和突现分析等,并绘制可视化知识图谱。结果与结论:①共纳入1914篇文献,近20年Theta爆发式经颅磁刺激研究量呈总体上升趋势,预计未来将继续保持研究热度。②发文量前3位的国家为美国、中国和意大利,机构为加拿大多伦多大学、英国伦敦大学和美国哈佛大学医学院;美国哈佛大学医学院的Pascual-leone,Alvaro研究成果最多,中国长庚大学的HUANG YZ被引频次最高;《NEURON》为影响力最大的期刊。③高频关键词、高被引文献和聚类主题结果显示,近20年Theta爆发式经颅磁刺激研究热点主要集中于:Theta爆发式经颅磁刺激对突触可塑性和神经生理活动的作用机制,Theta爆发式经颅磁刺激刺激不同脑区靶点的作用效果(包括运动皮质、背外侧前额叶皮质、前扣带皮质和小脑等),以及Theta爆发式经颅磁刺激对神经和精神疾病的疗效探讨(包括抑郁症、帕金森病运动障碍、脑卒中后运动障碍和认知障碍,以及阿尔茨海默病记忆障碍等)。此外,综述和临床试验类文献被引频次最高,未来可重点关注。④关键词突现、文献突现和关键词时间演化分析显示,“重度抑郁症、应用指南、评定量表、疗效、障碍、难治性抑郁症、Meta分析”等不仅是当前的研究热点,也是未来的研究趋势。⑤未来,Theta爆发式经颅磁刺激研究应加强核心作者和机构的区域性合作,发掘其在临床难治性疾病中的应用,通过结合前沿技术和优化刺激参数,实现Theta爆发式经颅磁刺激应用的精准化、个性化和最优化,解决更多临床难题。展开更多
基金supported by the National Natural Science Foundation of China(81770956,81371049,32471055 and 82171090)Project of Tianjin 131 Innovative Talent Team(201936)+4 种基金the Science and Technology Planning Project of Tianjin(21JCYBJC00780)the Science and Technology Fund for Health of Tianjin(TJWJ2023ZD008)Shanghai Municipal Science and Technology Major Project(2018SHZDZX01)ZJLab,Shanghai Center for Brain Science and Brain-Inspired Technology,the Lingang Laboratory(LG-QS-202203-12)Tianjin Key Medical Discipline(Specialty)Construction Project(TJYXZDXK‑016A).
文摘The visual cortex is an essential part of the brain for processing visual information.It exhibits structural and functional plasticity,which is crucial for adapting to complex visual environments.The quintessential manifestation of visual cortical plasticity is ocular dominance plasticity during the critical period,which involves numerous cellular and molecular events.While previous studies have emphasized the role of visual cortical neurons and their associated functional molecules in visual plasticity,recent findings have revealed that structural factors such as the extracellular matrix and glia are also involved.Investigating how these molecules interact to form a complex network that facilitates plasticity in the visual cortex is crucial to our understanding of the development of the visual system and the advancement of therapeutic strategies for visual disorders like amblyopia.
基金supported by the Graduate Degree Thesis Innovation Foundation of Central South University, No.2009BSXT050
文摘Nogo-A and Nogo receptor （NgR） expression in the visual cortex following a critical developmental period （postnatal days 20-60） has been previously shown. However, little is known regarding Nogo-A and NgR expression between postnatal day 0 and initiation of the critical period. The present study analyzed Nogo-A and NgR expression at four different time points： postnatal day 0 （P0）, before critical period （P14）, during critical period （P28）, and after critical period （P60）. Results showed significantly increased Nogo-A mRNA and protein expression levels in the visual cortex following birth, and expression levels remained steady between P28 and P60. NgR mRNA or protein expression was dramatically upregulated with age and peaked at P14 or P28, respectively, and maintained high expression to P60. In addition, Nogo-A and NgR expression was analyzed in each visual cortex layer in normal developing rats and rats with monocular deprivation. Monocular deprivation decreased Nogo-A and NgR mRNA and protein expression in the rat visual cortex, in particular in layers Ⅱ-Ⅲ and Ⅳ in the visual cortex contralateral to the deprived eye. These findings suggested that Nogo-A and NgR regulated termination of the critical period in experience- dependent visual cortical plasticity.
基金supported by grants from the National Natural Science Foundation of China(32130043 to X.Z.)the Scientific&Technological Innovation(STI)2030-Major Project(2022ZD0204900 to X.Z.)+1 种基金the National Natural Science Foundation of China(32400870 to Z.S.)the Fundamental Research Funds for the Central Universities(2243300002 to Z.S.).
文摘Critical periods(CPs)are defined as postnatal developmental windows during which brain circuits exhibit heightened sensitivity to altered experiences or sensory inputs,particularly during brain development in humans and animals.During the CP,experience-induced refinements of neural connections are crucial for establishing adaptive and mature brain functions,and aberrant CPs are often accompanied by many neurodevelopmental disorders(NDDs),including autism spectrum disorders and schizophrenia.Understanding neural mechanisms underlying the CP regulation is key to delineating the etiology of NDDs caused by abnormal postnatal neurodevelopment.Recent evidence from studies using innovative experimental tools has continuously revisited the inhibition-gating theory of CP to systematically elucidate the differential roles of distinct inhibitory circuits.Here,we provide a comprehensive review of classical experimental findings and emerging inhibitory-circuit regulation mechanisms of the CP,and further discuss how aberrant CP plasticity is associated with NDDs.
基金Supported by Chinese National Natural Science Found (grants Nos,39970252, 39770258, 30070254).
文摘Purpose: To study the property of LTP in layers Ⅱ～Ⅳof the rats visual cortex at different postnatal days induced by pairing low-frequency stimulation at layer Ⅳ with post synaptic depolarization in order to explore the synaptic and cellular mechanism of experience-dependent plasticity in the visual cortex.Methods: Postsynaptic currents (PSCs) of layers Ⅱ～Ⅳ in visual cortex slices of Wistar rats aged P0-29 d were recorded by patch-clamp whole cell recording method. Long-term potentiation (LTP) was induced by low-frequency stimulation (LFS) at 1Hz for 60～90 s.Each pulse of the LFS paired with depolarization of post-synaptic neurons to -20 mV.100μM APV, a kind of competitive N-methyl-d-aspartate (NMDA) receptor antagonist, was both applied to some slices to test the property of LTP.Results: 1. The LTP incidence was very low before P10d (5/34), and increased rapidly to the top at P15-24 d (17/28), then decreased sharply to 1/5 at P25-29 d, coinciding well with the critical period of plasticity of rat visual cortex. The LTP incidence of P15-29d (after eye opening, 18/33) was significantly higher than that of P0-14 d (before eye opening, 12/43, P ＜ 0.05). 2. Compared with non-APV applied group (30/76), LTP incidence of APV applied group (4/33) was significantly decreased (P ＜ 0.01 ). There were 4 Ⅳ-Ⅳ horizontal synapses. APV application could not block the LTP induction.Conclusions: 1. LTP was a reflection of naturally occurring, experience-dependent plasticity in rat visual cortex. The patterned visual stimuli received after eye opening might be an activation factor of the synaptic plasticity. 2. LTP of visual cortex induced by LFS in layer Ⅳ paired with postsynaptic depolarization was NMDA receptor dependent during the critical period of visual plasticity. However, there were LTP existed in Ⅳ-Ⅳ horizontal synapses which could not be blocked by 100μM APV.
基金supported by the National Natural Science Foundation of China,No.82271115(to MY).
文摘Synaptic plasticity is essential for maintaining neuronal function in the central nervous system and serves as a critical indicator of the effects of neurodegenerative disease.Glaucoma directly impairs retinal ganglion cells and their axons,leading to axonal transport dysfuntion,subsequently causing secondary damage to anterior or posterior ends of the visual system.Accordingly,recent evidence indicates that glaucoma is a degenerative disease of the central nervous system that causes damage throughout the visual pathway.However,the effects of glaucoma on synaptic plasticity in the primary visual cortex remain unclear.In this study,we established a mouse model of unilateral chronic ocular hypertension by injecting magnetic microbeads into the anterior chamber of one eye.We found that,after 4 weeks of chronic ocular hypertension,the neuronal somas were smaller in the superior colliculus and lateral geniculate body regions of the brain contralateral to the affected eye.This was accompanied by glial cell activation and increased expression of inflammatory factors.After 8 weeks of ocular hypertension,we observed a reduction in the number of excitatory and inhibitory synapses,dendritic spines,and activation of glial cells in the primary visual cortex contralateral to the affected eye.These findings suggest that glaucoma not only directly damages the retina but also induces alterations in synapses and dendritic spines in the primary visual cortex,providing new insights into the pathogenesis of glaucoma.
文摘Microglia are the resident macrophages of the central nervous system.Microglia possess varied morphologies and functions.Under normal physiological conditions,microglia mainly exist in a resting state and constantly monitor their microenvironment and survey neuronal and synaptic activity.Through the C1 q,C3 and CR3"Eat Me"and CD47 and SIRPα"Don't Eat Me"complement pathways,as well as other pathways such as CX3 CR1 signaling,resting microglia regulate synaptic pruning,a process crucial for the promotion of synapse formation and the regulation of neuronal activity and synaptic plasticity.By mediating synaptic pruning,resting microglia play an important role in the regulation of experience-dependent plasticity in the barrel cortex and visual cortex after whisker removal or monocular deprivation,and also in the regulation of learning and memory,including the modulation of memory strength,forgetfulness,and memory quality.As a response to brain injury,infection or neuroinflammation,microglia become activated and increase in number.Activated microglia change to an amoeboid shape,migrate to sites of inflammation and secrete proteins such as cytokines,chemokines and reactive oxygen species.These molecules released by microglia can lead to synaptic plasticity and learning and memory deficits associated with aging,Alzheimer's disease,traumatic brain injury,HIV-associated neurocognitive disorder,and other neurological or mental disorders such as autism,depression and post-traumatic stress disorder.With a focus mainly on recently published literature,here we reviewed the studies investigating the role of resting microglia in synaptic plasticity and learning and memory,as well as how activated microglia modulate disease-related plasticity and learning and memory deficits.By summarizing the function of microglia in these processes,we aim to provide an overview of microglia regulation of synaptic plasticity and learning and memory,and to discuss the possibility of microglia manipulation as a therapeutic to ameliorate cognitive deficits associated with aging,Alzheimer's disease,traumatic brain injury,HIV-associated neurocognitive disorder,and mental disorders.
基金Supported by the Suzhou Science and Technology Bureau(No.SKY2023175)the Project of State Key Laboratory of Radiation Medicine and Protection+6 种基金Soochow University(No.GZK1202309)the Advantage Subject Lifting Project(No.XKTJ-XK202412)the Suzhou Science and Education for Strengthening Healthcare(No.MSXM2024010)the Suzhou Medical Key Supported Disciplines(No.SZFCXK202118)the Youth Scientific Research Fund Project of Kunshan Hospital of Traditional Chinese Medicine(No.2024QNJJ06)the Postgraduate Research&Practice Innovation Program of Jiangsu Province(No.SJCX23_1673)the Undergraduate Training Program for Innovation and Entrepreneurship,Soochow University(No.202310285162Y).
文摘AIM:To investigate the postnatal development of parvalbumin(PV)-positive gamma-aminobutyric acid(GABA)interneurons and the co-expression of perineuronal nets(PNNs)and PV in the visual cortex of rats,as well as the regulatory effects of fluoxetine(FLX)treatment and binocular form deprivation(BFD)on these indices.METHODS:Wistar rats were assigned to three experimental cohorts:1)Age-related groups:postnatal week(PW)1,PW3,PW5,PW7,and PW9;2)FLX treatment duration groups:FLX 0W,FLX 2W,FLX 4W,FLX 6W,and FLX 8W;3)Intervention groups:control(Cont),FLX,BFD,and BFD+FLX.The levels of PNNs,PV,and PNNs/PV coexpression in the visual cortex were detected and analyzed.RESULTS:The density of PV-positive cells and the coexpression of PNNs and PV increased gradually with the maturation of the visual cortex(b=0.960,P<0.01).The ratio of PV-positive cells surrounded by PNNs to total PV-positive cells(PNNs+/PV+/total PV+)was significantly decreased in the FLX 4W group(χ^(2)=9.03,P=0.003).There was no significant difference in the PNNs+/PV+/total PV+ratio between the FLX and BFD groups(χ^(2)=1.08,P=0.161),but a significant difference was observed between the BFD+FLX group and the BFD group(χ^(2)=5.82,P<0.01).CONCLUSION:The number of PV-positive neurons and PNNs-surrounded PV neurons in the rat visual cortex increases postnatally and reaches adult levels by postnatal week 7.Chronic FLX treatment downregulates these expressions.Combined 4-week FLX treatment and BFD exerts a more significant inhibitory effect on the PNNs+/PV+/total PV+ratio than either intervention alone.
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.
文摘Objective:To report a case of anisometropic amblyopia reversal as a result of branch retinal vein occlusion (BRVO) occurring in the sound fellow eye.Methods:An adult patient with childhood anisometropic amblyopia was found to exhibit gradually visual acuity improvement in the amblyopic eye as the result of decreased visual acuity in the sound fellow eye.Results:Four years after the BRVO,the patient subsequently regained normal vision in the previously amblyopic eye.Conclusion:Visual plasticity is preserved in adults but may require special or stronger stimulation and possibly longer treatment time than during childhood.
文摘Background:Visual deficits,caused by ocular disease or trauma,can cause lasting damage.However,recent research has focused on neural plasticity as a means to regain visual functions.In order to better understand the involvement of neural plasticity and reorganization in partial vision restoration,we aim to evaluate the partial recovery of a visual deficit over time using two behavioural tests.In our study,a partial optic nerve crush(pONC)serves as an induced visual deficit,allowing for residual vision from surviving cells.Methods:Visual functions in C57BL/6 mice was measured using two behavioural tests prior to a bilateral pONC,then at various time points after the pONC.In this study,two injury intensities were used:a high intensity pONC with the full force of self-closing forceps,and a low intensity pONC,in which a calibrated space was left between the forceps at the closed position.The two behavioural tests consisted of the optomotor reflex(OMR)and the visual cliff(VC)tests.The OMR test measures the mouse’s tracking reflex in response to moving sinusoidal gratings.The VC test,on the other hand,evaluates exploratory behaviour,by simulating a cliff to observe the animal’s sense of depth perception.After the behavioural evaluation,surviving retinal ganglion cells were counted.Results:The high intensity pONC resulted in a total loss of visual acuity as measured by the OMR test,with no improvement in the following 4 weeks.However,the light intensity pONC showed the same initial loss,but recovery was observed as of day 3,and results in 40-60%recovery after 4 weeks.With the VC test,mice with intact vision will avoid the deep end,opting to spend more time in the shallow end.However,after both high and low intensity pONCs,this preference is no longer observed.Both groups show a return to the shallow end preference at day 14,though the low intensity pONC group showed a stronger preference similar to baseline performance.The percentage of surviving retinal ganglion cells was higher with the low intensity(68%)than with the high intensity(17%)pONC.Conclusions:There is evidence of visual recovery at the behavioural level following a pONC,though very little recovery was observed following a high intensity pONC,and only with the VC test.Therefore,a certain amount of residual retinal input may be required for recovery at the behavioural level.
基金supported by the National Natural Science Foundation of China(82271115,82471115)the Natural Science Foundation Team Project of Guangdong Province Grant(2015A030312016).
文摘Amblyopia is a neurodevelopmental vision disorder resulting from abnormal visual input during the critical period of visual development,such as strabismus,uncorrected anisometropia,high refractive errors,and form deprivation.It is frequently associated with reduced visual acuity and deficits in binocular vision.Traditional occlusion therapy for amblyopia has typically been restricted to infants and young children during the critical period of visual development,as it is believed to be ineffective for older children and adults due to the decreased plasticity of the mature brain.Our research group has concentrated on pivotal scientific issues in amblyopia,including quantitative methods for detecting binocular vision,especially interocular visual suppression,the mechanisms underlying binocular vision impairment in amblyopia,treatment methods and their evaluations for amblyopia,and visual plasticity and its neural mechanisms in amblyopia.This paper summarizes the visual mechanisms and treatment modalities of amblyopia based on our research and both domestic and foreign sources,while also looking forward to the future development of this field in light of existing problems.
文摘背景:相比于常规重复经颅磁刺激,Theta爆发式经颅磁刺激因具有刺激时间短、效率高、安全性好和效果持久等优势,正受到各领域学者的广泛关注,研究热度持续上升。目的:通过对近20年国际Theta爆发式经颅磁刺激研究进行文献计量学的可视化分析,梳理Theta爆发式经颅磁刺激研究的发展脉络,总结研究现状,揭示研究热点和发展趋势,为后续研究提供借鉴和参考。方法:检索Web of Science核心集数据库中2005年1月至2024年6月有关Theta爆发式经颅磁刺激的相关文献,应用CiteSpace软件进行年度发文量分析,国家、机构和作者合作共现分析,参考文献、期刊和作者共被引分析,关键词共现、聚类、时间演化和突现分析等,并绘制可视化知识图谱。结果与结论:①共纳入1914篇文献,近20年Theta爆发式经颅磁刺激研究量呈总体上升趋势,预计未来将继续保持研究热度。②发文量前3位的国家为美国、中国和意大利,机构为加拿大多伦多大学、英国伦敦大学和美国哈佛大学医学院;美国哈佛大学医学院的Pascual-leone,Alvaro研究成果最多,中国长庚大学的HUANG YZ被引频次最高;《NEURON》为影响力最大的期刊。③高频关键词、高被引文献和聚类主题结果显示,近20年Theta爆发式经颅磁刺激研究热点主要集中于:Theta爆发式经颅磁刺激对突触可塑性和神经生理活动的作用机制,Theta爆发式经颅磁刺激刺激不同脑区靶点的作用效果(包括运动皮质、背外侧前额叶皮质、前扣带皮质和小脑等),以及Theta爆发式经颅磁刺激对神经和精神疾病的疗效探讨(包括抑郁症、帕金森病运动障碍、脑卒中后运动障碍和认知障碍,以及阿尔茨海默病记忆障碍等)。此外,综述和临床试验类文献被引频次最高,未来可重点关注。④关键词突现、文献突现和关键词时间演化分析显示,“重度抑郁症、应用指南、评定量表、疗效、障碍、难治性抑郁症、Meta分析”等不仅是当前的研究热点,也是未来的研究趋势。⑤未来,Theta爆发式经颅磁刺激研究应加强核心作者和机构的区域性合作,发掘其在临床难治性疾病中的应用,通过结合前沿技术和优化刺激参数,实现Theta爆发式经颅磁刺激应用的精准化、个性化和最优化,解决更多临床难题。
