Very little is known about the effects of transcranial magnetic stimulation and rehabilitation training on pyramidal cell dendrites and synapses of the contralateral, unaffected sensorimotor cortex in a rat model of f...Very little is known about the effects of transcranial magnetic stimulation and rehabilitation training on pyramidal cell dendrites and synapses of the contralateral, unaffected sensorimotor cortex in a rat model of focal cerebral infarct. The present study was designed to explore the mechanisms underlying improved motor function via transcranial magnetic stimulation and rehabilitation training following cerebral infarction. Results showed that rehabilitation training or transcranial magnetic stimulation alone reduced neurological impairment in rats following cerebral infarction, as well as significantly increased synaptic curvatures and post-synaptic density in the non-injured cerebral hemisphere sensorimotor cortex and narrowed the synapse cleft width. In addition, the percentage of perforated synapses increased. The combination of transcranial magnetic stimulation and rehabilitation resulted in significantly increased total dendritic length, dendritic branching points, and dendritic density in layer V pyramidal cells of the non-injured cerebral hemisphere motor cortex. These results demonstrated that transcranial magnetic stimulation and rehabilitation training altered structural parameters of pyramidal cell dendrites and synapses in the non-injured cerebral hemisphere sensorimotor cortex, thereby improving the ability to compensate for neurological functions in rats following cerebral infarction.展开更多
Pain is one of the manifestations of hip disorder and has been proven to lead to the remodeling of somatotopic map plasticity in the cortex.However,most studies are volume-based which may lead to inaccurate anatomical...Pain is one of the manifestations of hip disorder and has been proven to lead to the remodeling of somatotopic map plasticity in the cortex.However,most studies are volume-based which may lead to inaccurate anatomical positioning of functional data.The methods that work on the cortical surface may be more sensitive than those using the full brain volume and thus be more suitable for map plasticity study.In this prospective cross-sectional study performed in Yueyang Hospital of Integrated Traditional Chinese and Western Medicine,Shanghai University of Traditional Chinese Medicine,China,20 patients with osteonecrosis of the femoral head(12 males and 8 females,aged 56.80±13.60 years)and 20 healthy controls(9 males and 11 females,aged 54.56±10.23 years)were included in this study.Data of resting-state functional magnetic resonance imaging were collected.The results revealed that compared with healthy controls,compared with the healthy controls,patients with osteonecrosis of the femoral head(ONFH)showed significantly increased surface-based regional homogeneity(Re Ho)in areas distributed mainly in the left dorsolateral prefrontal cortex,frontal eye field,right frontal eye field,and the premotor cortex and decreased surface-based Re Ho in the right primary motor cortex and primary sensory cortex.Regions showing significant differences in surfacebased Re Ho values between the healthy controls and patients with ONFH were defined as the regions of interests.Seed-based functional connectivity was performed to investigate interregional functional synchronization.When the areas with decreased surface-based Re Ho in the frontal eye field and right premotor cortex were used as the regions of interest,compared with the healthy controls,the patients with ONFH displayed increased functional connectivity in the right middle frontal cortex and right inferior parietal cortex and decreased functional connectivity in the right precentral cortex and right middle occipital cortex.Compared with healthy controls,patients with ONFH showed significantly decreased cortical thickness in the para-insular area,posterior insular area,anterior superior temporal area,frontal eye field and supplementary motor cortex and reduced volume of subcortical gray matter nuclei in the right nucleus accumbens.These findings suggest that hip disorder patients showed cortical plasticity changes,mainly in sensorimotor-and pain-related regions.This study was approved by the Medical Ethics Committee of Yueyang Hospital of Integrated Traditional Chinese and Western Medicine,Shanghai University of Traditional Chinese Medicine(approval No.2018-041)on August 1,2018.展开更多
Following a spinal cord injury,there are usually a number of neural pathways that remain intact in the spinal cord.These residual nerve fibers are important,as they could be used to reconstruct the neural circuits tha...Following a spinal cord injury,there are usually a number of neural pathways that remain intact in the spinal cord.These residual nerve fibers are important,as they could be used to reconstruct the neural circuits that enable motor function.Our group previously designed a novel magnetic stimulation protocol,targeting the motor cortex and the spinal nerve roots,that led to significant improvements in locomotor function in patients with a chronic incomplete spinal cord injury.Here,we investigated how nerve root magnetic stimulation contributes to improved locomotor function using a rat model of spinal cord injury.Rats underwent surgery to clamp the spinal cord at T10;three days later,the rats were treated with repetitive magnetic stimulation(5 Hz,25 pulses/train,20 pulse trains)targeting the nerve roots at the L5-L6 vertebrae.The treatment was repeated five times a week over a period of three weeks.We found that the nerve root magnetic stimulation improved the locomotor function and enhanced nerve conduction in the injured spinal cord.In addition,the nerve root magnetic stimulation promoted the recovery of synaptic ultrastructure in the sensorimotor cortex.Overall,the results suggest that nerve root magnetic stimulation may be an effective,noninvasive method for mobilizing the residual spinal cord pathways to promote the recovery of locomotor function.展开更多
The study aims to confirm the neuroregenerative effects of bacterial melanin （BM） on central nervous system injury using a special staining method based on the detection of Ca^2＋-dependent acid phosphatase activity...The study aims to confirm the neuroregenerative effects of bacterial melanin （BM） on central nervous system injury using a special staining method based on the detection of Ca^2＋-dependent acid phosphatase activity. Twenty-four rats were randomly assigned to undergo either unilateral destruction of sensorimotor cortex （group I; n = 12） or unilateral rubrospinal tract transection at the cervical level （C3-4） （group II; n = 12）. In each group, six rats were randomly selected after surgery to undergo intramuscular injection of BM solution （BM subgroup） and the remaining six rats were intramuscularly in）ected with saline （saline subgroup）. Neurological testing confirmed that BM accelerated the recovery of motor function in rats from both BM and saline subgroups. Two months after surgery, Ca^2＋-dependent acid phosphatase activity detection in combination with Chilingarian＇s calcium adenoside triphosphate method revealed that BM stimulated the sprouting of fibers and dilated the capillaries in the brain and spinal cord. These results suggest that BM can promote the recovery of motor function of rats with central nervous system injury; and detection of Ca^2＋-dependent acid phosphatase activity is a fast and easy method used to study the regeneration-promoting effects of BM on the injured central nervous system.展开更多
Axonal regeneration plays an important role in functional recovery after nervous system damage.However,after axonal injury in mammals,regeneration is often poor.The deletion of Krüppel-like factor-4(Klf4)has been...Axonal regeneration plays an important role in functional recovery after nervous system damage.However,after axonal injury in mammals,regeneration is often poor.The deletion of Krüppel-like factor-4(Klf4)has been shown to promote axonal regeneration in retinal ganglion cells.However,the effects of Klf4 deletion on the corticospinal tract and peripheral nervous system are unknown.In this study,using a mouse model of sciatic nerve injury,we show that the expression of Klf4 in dorsal root ganglion sensory neurons was significantly reduced after peripheral axotomy,suggesting that the regeneration of the sciatic nerve is associated with Klf4.In vitro,dorsal root ganglion sensory neurons with Klf4 knockout exhibited significantly enhanced axonal regeneration.Furthermore,the regeneration of the sciatic nerve was enhanced in vivo following Klf4 knockout.Finally,AAV-Cre virus was used to knockout the Klf4 gene in the cortex.The deletion of Klf4 enhanced regeneration of the corticospinal tract in mice with spinal cord injury.Together,our findings suggest that regulating KLF4 activity in neurons is a potential strategy for promoting axonal regeneration and functional recovery after nervous system injury.This study was approved by the Animal Ethics Committee at Soochow University,China(approval No.SUDA20200316A01).展开更多
We performed functional MRI examinations in six right-handed healthy subjects.During functional MRI scanning,transcranial direct current stimulation was delivered with the anode over the right primary sensorimotor cor...We performed functional MRI examinations in six right-handed healthy subjects.During functional MRI scanning,transcranial direct current stimulation was delivered with the anode over the right primary sensorimotor cortex and the cathode over the left primary sensorimotor cortex using dual-hemispheric transcranial direct current stimulation.This was compared to a cathode over the left supraorbital area using conventional single-hemispheric transcranial direct current stimulation. Voxel counts and blood oxygenation level-dependent signal intensities in the right primary sensorimotor cortex regions were estimated and compared between the two transcranial direct current stimulation conditions.Our results showed that dual-hemispheric transcranial direct current stimulation induced greater cortical activities than single-hemispheric transcranial direct current stimulation.These findings suggest that dual-hemispheric transcranial direct current stimulation may provide more effective cortical stimulation than single-hemispheric transcranial direct current stimulation.展开更多
On the slices of sensorimotor and frontal cortex in layer V of guinea pigs the diversity of neuronal spontaneous activity, the mechanism of its origin and functional specificity were studied. In both regions, neurons ...On the slices of sensorimotor and frontal cortex in layer V of guinea pigs the diversity of neuronal spontaneous activity, the mechanism of its origin and functional specificity were studied. In both regions, neurons that did not have spontaneous activity predominated (39% in the sensorimotor cortex and 32% in the frontal cortex) over neurons with any other firing levels. The iontophoretic application of the excitatory transmitter, glutamate, caused activation spike reactions in all registered neurons;moreover, short-term activation reactions to glutamate had a significantly longer after-discharge in neurons of the frontal cortex (up to 2500 ms and more) compared to reactions of neurons of the sensorimotor region. This means that postexcitatory hyperpolarization in nerve cells of the frontal cortex is less expressed and, therefore, they have a lower density of K+ channels on their membranes. With an increase in the level of spontaneous activity, K+ membrane permeability decreases, which is confirmed by the appearance of a long activation reaction to acetylcholine (which blocks K+ channels), exactly when spontaneous firing appears in “silent” neurons. Despite the fact that spontaneous activity is formed by glutamatergic excitation, its considerable diversity is associated with the structural and membrane characteristics of neurons, which determine the different degrees of EPSPs attenuation on the way of moving along dendrites. Acetylcholine regulates this process in different ways, in accordance with different states of K+ membrane permeability. Therefore, the lower content of K+ channels on the membranes of neurons of the frontal cortex does not allow regulating spontaneous activity in the same range as occurs in neurons of the sensorimotor region. The presence of a high proportion of spontaneously inactive neurons in the cortex (higher in the sensorimotor cortex) suggests that cortical neurons are generally characterized by a high density of K+ channels and a significant increase in firing response to acetylcholine, while spontaneously active neurons cannot control the spontaneous activity in a wide range.展开更多
The Brodmann area(BA)-based map is one of the most widely used cortical maps for studies of human brain functions and in clinical practice;however,the molecular architecture of BAs remains unknown.The present study pr...The Brodmann area(BA)-based map is one of the most widely used cortical maps for studies of human brain functions and in clinical practice;however,the molecular architecture of BAs remains unknown.The present study provided a global multiregional proteomic map of the human cerebral cortex by analyzing 29 BAs.These 29 BAs were grouped into 6 clusters based on similarities in proteomic patterns:the motor and sensory cluster,vision cluster,auditory and Broca’s area cluster,Wernicke’s area cluster,cingulate cortex cluster,and heterogeneous function cluster.We identified 474 cluster-specific and 134 BA-specific signature proteins whose functions are closely associated with specialized functions and disease vulnerability of the corresponding cluster or BA.The findings of the present study could provide explanations for the functional connections between the anterior cingulate cortex and sensorimotor cortex and for anxiety-related function in the sensorimotor cortex.The brain transcriptome and proteome comparison indicates that they both could reflect the function of cerebral cortex,but show different characteristics.These proteomic data are publicly available at the Human Brain Proteome Atlas(www.brain-omics.com).Our results may enhance our understanding of the molecular basis of brain functions and provide an important resource to support human brain research.展开更多
Establishment of animal models of schizophrenia is critical for both understanding the mechanisms underlying this severe mental disease and developing new antipsychotics. This paper starts from the theoretical root of...Establishment of animal models of schizophrenia is critical for both understanding the mechanisms underlying this severe mental disease and developing new antipsychotics. This paper starts from the theoretical root of sensory gating, the 損rotection-of-processing?theory, then thoroughly describes the representative studies over the past decade on the mechanism underlying prepulse inhibition and on those underlying modulation of prepulse inhibition, which is the normal startle suppression caused by the weak stimulus preceding the intense startling stimulus. The main methods for inducing prepulse inhibition deficits in experimental animals include: ⅰ) modulations of neuro- transmission that are closely associated with schizophrenia; ⅱ) focal lesions or pharmacological manipulations of brain structures in the cortico-striato-pallido-pontine circuit; and ⅲ) maternal deprivation or social isolation. Six essential topics for studies in modeling schizophrenia are suggested at the last part of this review.展开更多
基金Yantai Science and Technology Development Projects, No. 2008142-5
文摘Very little is known about the effects of transcranial magnetic stimulation and rehabilitation training on pyramidal cell dendrites and synapses of the contralateral, unaffected sensorimotor cortex in a rat model of focal cerebral infarct. The present study was designed to explore the mechanisms underlying improved motor function via transcranial magnetic stimulation and rehabilitation training following cerebral infarction. Results showed that rehabilitation training or transcranial magnetic stimulation alone reduced neurological impairment in rats following cerebral infarction, as well as significantly increased synaptic curvatures and post-synaptic density in the non-injured cerebral hemisphere sensorimotor cortex and narrowed the synapse cleft width. In addition, the percentage of perforated synapses increased. The combination of transcranial magnetic stimulation and rehabilitation resulted in significantly increased total dendritic length, dendritic branching points, and dendritic density in layer V pyramidal cells of the non-injured cerebral hemisphere motor cortex. These results demonstrated that transcranial magnetic stimulation and rehabilitation training altered structural parameters of pyramidal cell dendrites and synapses in the non-injured cerebral hemisphere sensorimotor cortex, thereby improving the ability to compensate for neurological functions in rats following cerebral infarction.
基金supported by National Key R&D Program of China,No.2018YFC2001600(to JGX)the National Natural Science Foundation of China,Nos.81802249(to XYH),81871836(to MXZ)+4 种基金a grant from Shanghai Science and Technology Committee of China,Nos.18511108300(to JGX),18441903903900(to XYH),18441903800(to MXZ)Three-Year Action Plan for Traditional Chinese Medicine Development from Shanghai Municipal Health Commission of China,No.ZY(2018-2020)-ZWB-1001-CPJS49(to BL)ZY(2018-2020)-RCPY-3007(to JM)Traditional Chinese Medicine Diagnosis and Treatment Technology Improvement Project from Shanghai Municipal Commission of Health and Family Planning of China,No.Zyjx-2017006(to BL)Special Project of Postgraduate Innovation Training of China,No.A1-GY20-204-0107(to JM)。
文摘Pain is one of the manifestations of hip disorder and has been proven to lead to the remodeling of somatotopic map plasticity in the cortex.However,most studies are volume-based which may lead to inaccurate anatomical positioning of functional data.The methods that work on the cortical surface may be more sensitive than those using the full brain volume and thus be more suitable for map plasticity study.In this prospective cross-sectional study performed in Yueyang Hospital of Integrated Traditional Chinese and Western Medicine,Shanghai University of Traditional Chinese Medicine,China,20 patients with osteonecrosis of the femoral head(12 males and 8 females,aged 56.80±13.60 years)and 20 healthy controls(9 males and 11 females,aged 54.56±10.23 years)were included in this study.Data of resting-state functional magnetic resonance imaging were collected.The results revealed that compared with healthy controls,compared with the healthy controls,patients with osteonecrosis of the femoral head(ONFH)showed significantly increased surface-based regional homogeneity(Re Ho)in areas distributed mainly in the left dorsolateral prefrontal cortex,frontal eye field,right frontal eye field,and the premotor cortex and decreased surface-based Re Ho in the right primary motor cortex and primary sensory cortex.Regions showing significant differences in surfacebased Re Ho values between the healthy controls and patients with ONFH were defined as the regions of interests.Seed-based functional connectivity was performed to investigate interregional functional synchronization.When the areas with decreased surface-based Re Ho in the frontal eye field and right premotor cortex were used as the regions of interest,compared with the healthy controls,the patients with ONFH displayed increased functional connectivity in the right middle frontal cortex and right inferior parietal cortex and decreased functional connectivity in the right precentral cortex and right middle occipital cortex.Compared with healthy controls,patients with ONFH showed significantly decreased cortical thickness in the para-insular area,posterior insular area,anterior superior temporal area,frontal eye field and supplementary motor cortex and reduced volume of subcortical gray matter nuclei in the right nucleus accumbens.These findings suggest that hip disorder patients showed cortical plasticity changes,mainly in sensorimotor-and pain-related regions.This study was approved by the Medical Ethics Committee of Yueyang Hospital of Integrated Traditional Chinese and Western Medicine,Shanghai University of Traditional Chinese Medicine(approval No.2018-041)on August 1,2018.
基金supported by the National Natural Science Foundation of China(General Program),Nos.81772453,81974358(both to DSX).
文摘Following a spinal cord injury,there are usually a number of neural pathways that remain intact in the spinal cord.These residual nerve fibers are important,as they could be used to reconstruct the neural circuits that enable motor function.Our group previously designed a novel magnetic stimulation protocol,targeting the motor cortex and the spinal nerve roots,that led to significant improvements in locomotor function in patients with a chronic incomplete spinal cord injury.Here,we investigated how nerve root magnetic stimulation contributes to improved locomotor function using a rat model of spinal cord injury.Rats underwent surgery to clamp the spinal cord at T10;three days later,the rats were treated with repetitive magnetic stimulation(5 Hz,25 pulses/train,20 pulse trains)targeting the nerve roots at the L5-L6 vertebrae.The treatment was repeated five times a week over a period of three weeks.We found that the nerve root magnetic stimulation improved the locomotor function and enhanced nerve conduction in the injured spinal cord.In addition,the nerve root magnetic stimulation promoted the recovery of synaptic ultrastructure in the sensorimotor cortex.Overall,the results suggest that nerve root magnetic stimulation may be an effective,noninvasive method for mobilizing the residual spinal cord pathways to promote the recovery of locomotor function.
基金supported by the Armenian National Science and Education Fund for Project in New York,USA(No.ANSEF biotech-4241)
文摘The study aims to confirm the neuroregenerative effects of bacterial melanin （BM） on central nervous system injury using a special staining method based on the detection of Ca^2＋-dependent acid phosphatase activity. Twenty-four rats were randomly assigned to undergo either unilateral destruction of sensorimotor cortex （group I; n = 12） or unilateral rubrospinal tract transection at the cervical level （C3-4） （group II; n = 12）. In each group, six rats were randomly selected after surgery to undergo intramuscular injection of BM solution （BM subgroup） and the remaining six rats were intramuscularly in）ected with saline （saline subgroup）. Neurological testing confirmed that BM accelerated the recovery of motor function in rats from both BM and saline subgroups. Two months after surgery, Ca^2＋-dependent acid phosphatase activity detection in combination with Chilingarian＇s calcium adenoside triphosphate method revealed that BM stimulated the sprouting of fibers and dilated the capillaries in the brain and spinal cord. These results suggest that BM can promote the recovery of motor function of rats with central nervous system injury; and detection of Ca^2＋-dependent acid phosphatase activity is a fast and easy method used to study the regeneration-promoting effects of BM on the injured central nervous system.
基金This study was supported by the National Natural Science Foundation of China,Nos.81571189,81772353(to Saijilafu).
文摘Axonal regeneration plays an important role in functional recovery after nervous system damage.However,after axonal injury in mammals,regeneration is often poor.The deletion of Krüppel-like factor-4(Klf4)has been shown to promote axonal regeneration in retinal ganglion cells.However,the effects of Klf4 deletion on the corticospinal tract and peripheral nervous system are unknown.In this study,using a mouse model of sciatic nerve injury,we show that the expression of Klf4 in dorsal root ganglion sensory neurons was significantly reduced after peripheral axotomy,suggesting that the regeneration of the sciatic nerve is associated with Klf4.In vitro,dorsal root ganglion sensory neurons with Klf4 knockout exhibited significantly enhanced axonal regeneration.Furthermore,the regeneration of the sciatic nerve was enhanced in vivo following Klf4 knockout.Finally,AAV-Cre virus was used to knockout the Klf4 gene in the cortex.The deletion of Klf4 enhanced regeneration of the corticospinal tract in mice with spinal cord injury.Together,our findings suggest that regulating KLF4 activity in neurons is a potential strategy for promoting axonal regeneration and functional recovery after nervous system injury.This study was approved by the Animal Ethics Committee at Soochow University,China(approval No.SUDA20200316A01).
基金supported by a National Research Foundation of Korea Grant funded by the Korean Government,No.2009-0064682
文摘We performed functional MRI examinations in six right-handed healthy subjects.During functional MRI scanning,transcranial direct current stimulation was delivered with the anode over the right primary sensorimotor cortex and the cathode over the left primary sensorimotor cortex using dual-hemispheric transcranial direct current stimulation.This was compared to a cathode over the left supraorbital area using conventional single-hemispheric transcranial direct current stimulation. Voxel counts and blood oxygenation level-dependent signal intensities in the right primary sensorimotor cortex regions were estimated and compared between the two transcranial direct current stimulation conditions.Our results showed that dual-hemispheric transcranial direct current stimulation induced greater cortical activities than single-hemispheric transcranial direct current stimulation.These findings suggest that dual-hemispheric transcranial direct current stimulation may provide more effective cortical stimulation than single-hemispheric transcranial direct current stimulation.
基金supported by grants from National Basic Research Program of China(2015CB856400,2015CB351701)The National Natural Science Foundation of China(81501158,31730039,31671133)+1 种基金The National Major Scientific Instruments and Equipment Development Project(ZDYZ2015-2)The Chinese Academy of Sciences Strategic Priority Research Program B grants(XDBS32000000)~~
文摘在睡眠剥夺(sleep deprivation,SD)过程中,人类大脑的神经活动和警觉水平如何受到影响,尤其是感觉运动和视觉系统,目前仍是研究的热点.静息状态功能磁共振成像(resting state functional magnetic resonance imaging,rf MRI)作为一种反映人脑自发活动的非侵入式成像技术,在睡眠剥夺的研究中得到了广泛应用.本研究采用9次重复rf MRI和心理运动警觉任务(psychomotor vigilance task,PVT),以探索23名志愿者在整个36 h的睡眠剥夺过程中神经活动和警觉水平的变化.采用基于PVT的平均反应时间(mean reaction time,MRT)和失效率(lapses ratio,LR)评估警觉水平的变化;采用基于rf MRI的区域同质性(region homogeneity,Re Ho)和低频波动幅度(amplitude of low frequency fluctuation,ALFF)评估大脑神经活动变化.结果表明,感觉运动网络(sensorimotor network,SMN)和视觉区域(visual network,VN)是受到睡眠剥夺影响最严重的区域.我们采用组独立成分分析(group independent component analysis,GICA)将视觉相关区域划分为视觉Ⅰ区、视觉Ⅱ区、视觉关联区,并从解剖自动标记(anatomical automatic labeling,AAL)模板中提取运动感觉相关区域,包括中央前/中央后回、中央旁小叶和辅助运动区.研究发现,睡眠剥夺后16~30 h脑神经活动及警惕性下降.采用2×3重复测量方差分析,探讨睡眠压力、昼夜节律及其交互作用对感觉运动相关和视觉相关脑区神经活动的影响.观察到睡眠压力与交互作用对感觉运动相关区域和视觉相关区域有显著影响.采用皮尔逊相关系数评估警觉水平变化与感觉运动相关和视觉相关脑区神经活动变化的关系.睡眠剥夺期间所有感觉运动相关区域的神经活动变化与警觉变化均存在显著的相关关系.研究结果证实,睡眠剥夺从第一天24:00开始改变SMN和VN的警戒水平和神经活动,睡眠压力和昼夜节律在睡眠剥夺期间调节SMN和VN的神经活动.此外,昼夜节律的效应受到睡眠压力的显著调节.感觉运动相关区域和视觉相关区域的增强导致他们远程连接的减弱,这可能是睡眠剥夺期间响应时间变慢的原因.
文摘On the slices of sensorimotor and frontal cortex in layer V of guinea pigs the diversity of neuronal spontaneous activity, the mechanism of its origin and functional specificity were studied. In both regions, neurons that did not have spontaneous activity predominated (39% in the sensorimotor cortex and 32% in the frontal cortex) over neurons with any other firing levels. The iontophoretic application of the excitatory transmitter, glutamate, caused activation spike reactions in all registered neurons;moreover, short-term activation reactions to glutamate had a significantly longer after-discharge in neurons of the frontal cortex (up to 2500 ms and more) compared to reactions of neurons of the sensorimotor region. This means that postexcitatory hyperpolarization in nerve cells of the frontal cortex is less expressed and, therefore, they have a lower density of K+ channels on their membranes. With an increase in the level of spontaneous activity, K+ membrane permeability decreases, which is confirmed by the appearance of a long activation reaction to acetylcholine (which blocks K+ channels), exactly when spontaneous firing appears in “silent” neurons. Despite the fact that spontaneous activity is formed by glutamatergic excitation, its considerable diversity is associated with the structural and membrane characteristics of neurons, which determine the different degrees of EPSPs attenuation on the way of moving along dendrites. Acetylcholine regulates this process in different ways, in accordance with different states of K+ membrane permeability. Therefore, the lower content of K+ channels on the membranes of neurons of the frontal cortex does not allow regulating spontaneous activity in the same range as occurs in neurons of the sensorimotor region. The presence of a high proportion of spontaneously inactive neurons in the cortex (higher in the sensorimotor cortex) suggests that cortical neurons are generally characterized by a high density of K+ channels and a significant increase in firing response to acetylcholine, while spontaneously active neurons cannot control the spontaneous activity in a wide range.
基金supported by the Institute of Basic Medical Sciences,Chinese Academy of Medical Sciences,Neuroscience Center,the China Human Brain Banking Consortiumsupported by the National Key R&D Program of China(Grant Nos.2016YFC1306300 and 2018YFC0910202)+10 种基金the National Natural Science Foundation of China(Grant Nos.30970650,31200614,31400669,81371515,81170665,and 81560121)Beijing Medical Research(Grant No.2018-7)Beijing Natural Science Foundation(Grant No.7173264 and 7172076)Beijing cooperative construction project(Grant No.110651103Beijing Science Program for the Top Young(Grant No.2015000021223TD04)Beijing Normal University(Grant No.11100704)Peking Union Medical College Hospital(Grant No.2016-2.27)CAMS Innovation Fund for Medical Sciences(Grant No.2017-I2M-1-009)the CAMS special basic research fund for central public research institutes(Grant No.2017PT310004)Biologic Medicine Information Center of ChinaNational Scientific Data Sharing Platform for Population and Health。
文摘The Brodmann area(BA)-based map is one of the most widely used cortical maps for studies of human brain functions and in clinical practice;however,the molecular architecture of BAs remains unknown.The present study provided a global multiregional proteomic map of the human cerebral cortex by analyzing 29 BAs.These 29 BAs were grouped into 6 clusters based on similarities in proteomic patterns:the motor and sensory cluster,vision cluster,auditory and Broca’s area cluster,Wernicke’s area cluster,cingulate cortex cluster,and heterogeneous function cluster.We identified 474 cluster-specific and 134 BA-specific signature proteins whose functions are closely associated with specialized functions and disease vulnerability of the corresponding cluster or BA.The findings of the present study could provide explanations for the functional connections between the anterior cingulate cortex and sensorimotor cortex and for anxiety-related function in the sensorimotor cortex.The brain transcriptome and proteome comparison indicates that they both could reflect the function of cerebral cortex,but show different characteristics.These proteomic data are publicly available at the Human Brain Proteome Atlas(www.brain-omics.com).Our results may enhance our understanding of the molecular basis of brain functions and provide an important resource to support human brain research.
基金This work was supported by the National Natural Sciences Foundation of China(Grant No.30200080)the Ministry of Science and Technology of China(Grant No.2002CCA01000)the Ministry of Education of China(Grant No.02170).
文摘Establishment of animal models of schizophrenia is critical for both understanding the mechanisms underlying this severe mental disease and developing new antipsychotics. This paper starts from the theoretical root of sensory gating, the 損rotection-of-processing?theory, then thoroughly describes the representative studies over the past decade on the mechanism underlying prepulse inhibition and on those underlying modulation of prepulse inhibition, which is the normal startle suppression caused by the weak stimulus preceding the intense startling stimulus. The main methods for inducing prepulse inhibition deficits in experimental animals include: ⅰ) modulations of neuro- transmission that are closely associated with schizophrenia; ⅱ) focal lesions or pharmacological manipulations of brain structures in the cortico-striato-pallido-pontine circuit; and ⅲ) maternal deprivation or social isolation. Six essential topics for studies in modeling schizophrenia are suggested at the last part of this review.
