Restraint water-immersion stress(RWIS), a compound stress model, has been widely used to induce acute gastric ulceration in rats. A wealth of evidence suggests that the central nucleus of the amygdala(CEA) is a focal ...Restraint water-immersion stress(RWIS), a compound stress model, has been widely used to induce acute gastric ulceration in rats. A wealth of evidence suggests that the central nucleus of the amygdala(CEA) is a focal region for mediating the biological response to stress. Different stressors induce distinct alterations of neuronal activity in the CEA; however, few studies have reported the characteristics of CEA neuronal activity induced by RWIS. Therefore, we explored this issue using immunohistochemistry and in vivo extracellular single-unit recording. Our results showed that RWIS and restraint stress(RS) differentially changed the c-Fos expression and firing properties of neurons in the medial CEA. In addition,RWIS, but not RS, induced the activation of corticotropinreleasing hormone neurons in the CEA. These findings suggested that specific neuronal activation in the CEA is involved in the formation of RWIS-induced gastric ulcers.This study also provides a possible theoretical explanation for the different gastric dysfunctions induced by different stressors.展开更多
Neuronal ensemble activity codes working memory.In this work,we developed a neuronal ensemble sparse coding method,which can effectively reduce the dimension of the neuronal activity and express neural coding.Multicha...Neuronal ensemble activity codes working memory.In this work,we developed a neuronal ensemble sparse coding method,which can effectively reduce the dimension of the neuronal activity and express neural coding.Multichannel spike trains were recorded in rat prefrontal cortex during a work memory task in Y-maze.As discretesignals,spikes were transferred into cont inuous signals by estinating entropy.Then the normalized continuous signals were decomposed via non-negative sparse met hod.The non-negative components were extracted to reconstruct a low-dimensional ensemble,while none of the feature components were missed.The results showed that,for well-trained rats,neuronal ensemble activities in the prefrontal cortex changed dynamically during the.working memory task.And the neuronal ensemble is more explicit via using non-negative sparse coding.Our results indicate that the neuronal ensemblesparse coding method can effectively reduce the dimnension of neuronal activity and it is a useful tool to express neural coding.展开更多
Neuronal activity,synaptic transmission,and molecular changes in the basolateral amygdala play critical roles in fear memory.Cylindromatosis(CYLD)is a deubiquitinase that negatively regulates the nuclear factor kappa-...Neuronal activity,synaptic transmission,and molecular changes in the basolateral amygdala play critical roles in fear memory.Cylindromatosis(CYLD)is a deubiquitinase that negatively regulates the nuclear factor kappa-B pathway.CYLD is well studied in non-neuronal cells,yet underinvestigated in the brain,where it is highly expressed.Emerging studies have shown involvement of CYLD in the remodeling of glutamatergic synapses,neuroinflammation,fear memory,and anxiety-and autism-like behaviors.However,the precise role of CYLD in glutamatergic neurons is largely unknown.Here,we first proposed involvement of CYLD in cued fear expression.We next constructed transgenic model mice with specific deletion of Cyld from glutamatergic neurons.Our results show that glutamatergic CYLD deficiency exaggerated the expression of cued fear in only male mice.Further,loss of CYLD in glutamatergic neurons resulted in enhanced neuronal activation,impaired excitatory synaptic transmission,and altered levels of glutamate receptors accompanied by over-activation of microglia in the basolateral amygdala of male mice.Altogether,our study suggests a critical role of glutamatergic CYLD in maintaining normal neuronal,synaptic,and microglial activation.This may contribute,at least in part,to cued fear expression.展开更多
The complex morphological,anatomical,physiological,and chemical mechanisms within the aging brain have been the hot topic of research for centuries.The aging process alters the brain structure that affects functions a...The complex morphological,anatomical,physiological,and chemical mechanisms within the aging brain have been the hot topic of research for centuries.The aging process alters the brain structure that affects functions and cognitions,but the worsening of such processes contributes to the pathogenesis of neurodegenerative disorders,such as Alzheimer's disease.Beyond these observable,mild morphological shifts,significant functional modifications in neurotransmission and neuronal activity critically influence the aging brain.Understanding these changes is important for maintaining cognitive health,especially given the increasing prevalence of age-related conditions that affect cognition.This review aims to explore the age-induced changes in brain plasticity and molecular processes,differentiating normal aging from the pathogenesis of Alzheimer's disease,thereby providing insights into predicting the risk of dementia,particularly Alzheimer's disease.展开更多
Delirium is a severe acute neuropsychiatric syndrome that commonly occurs in the elderly and is considered an independent risk factor for later dementia.However,given its inherent complexity,few animal models of delir...Delirium is a severe acute neuropsychiatric syndrome that commonly occurs in the elderly and is considered an independent risk factor for later dementia.However,given its inherent complexity,few animal models of delirium have been established and the mechanism underlying the onset of delirium remains elusive.Here,we conducted a comparison of three mouse models of delirium induced by clinically relevant risk factors,including anesthesia with surgery(AS),systemic inflammation,and neurotransmission modulation.We found that both bacterial lipopolysaccharide(LPS)and cholinergic receptor antagonist scopolamine(Scop)induction reduced neuronal activities in the delirium-related brain network,with the latter presenting a similar pattern of reduction as found in delirium patients.Consistently,Scop injection resulted in reversible cognitive impairment with hyperactive behavior.No loss of cholinergic neurons was found with treatment,but hippocampal synaptic functions were affected.These findings provide further clues regarding the mechanism underlying delirium onset and demonstrate the successful application of the Scop injection model in mimicking delirium-like phenotypes in mice.展开更多
Chronic stress leads to many psychiatric disorders,including social and anxiety disorders that are associated with over-activation of neurons in the basolateral amygdala(BLA).However,not all individuals develop psychi...Chronic stress leads to many psychiatric disorders,including social and anxiety disorders that are associated with over-activation of neurons in the basolateral amygdala(BLA).However,not all individuals develop psychiatric diseases,many showing considerable resilience against stress exposure.Whether BLA neuronal activity is involved in regulating an individual’s vulnerability to stress remains elusive.In this study,using a mouse model of chronic social defeat stress(CSDS),we divided the mice into susceptible and resilient subgroups based on their social interaction behavior.Using in vivo fiber photometry and in vitro patch-clamp recording,we showed that CSDS persistently(after 20 days of recovery from stress)increased BLA neuronal activity in all the mice regardless of their susceptible or resilient nature,although impaired social interaction behavior was only observed in susceptible mice.Increased anxiety-like behavior,on the other hand,was evident in both groups.Notably,the CSDS-induced increase of BLA neuronal activity correlated well with the heightened anxiety-like but not the social avoidance behavior in mice.These findings provide new insight to our understanding of the role of neuronal activity in the amygdala in mediating stress-related psychiatric disorders.展开更多
As a second messenger in signal transduction,calcium ion plays a very important role in neuronal information processing and integrating.Limited by the imaging technique,it is difficult to simultaneously perform deep t...As a second messenger in signal transduction,calcium ion plays a very important role in neuronal information processing and integrating.Limited by the imaging technique,it is difficult to simultaneously perform deep tissue imaging and measure intracellular free calcium concentration([Ca^(2+)]i)in different compartments of neurons in brain slice noncollinearly.By means of random access two-photon microscopy,which provides high optical penetration into tissues and low photo damage,we successfully measured[Ca^(2+)]i of different parts of pyramidal neurons in neocortical layer V in rat brain slices with high spatial and temporal resolution.Combining the patch clamp technique,we stimulated the soma with depolarizing current and explored the dynamics of calcium in pyramidal neurons.展开更多
Disorder of consciousness （DOC） is one of the most serious sequelae of brain injury, and is challenging for neurologists and rehabilitation special- ists to manage because of its refractory nature （Whyte et al., 2...Disorder of consciousness （DOC） is one of the most serious sequelae of brain injury, and is challenging for neurologists and rehabilitation special- ists to manage because of its refractory nature （Whyte et al., 2013）. Acu- puncture is a traditional Chinese medicine technique that is often used to help improve the level of consciousness in patients with DOC. However, the responses to stimulation of acupoints in patients with DOC are not fully understood.展开更多
Totally three articles focusing on Schisandra N-butanol extract effects on hippocampal CA1 synaptic morphology and plasticity in ovarectomized mice, as well as catalpol and GBE50 effects on neuronal synaptic plasticit...Totally three articles focusing on Schisandra N-butanol extract effects on hippocampal CA1 synaptic morphology and plasticity in ovarectomized mice, as well as catalpol and GBE50 effects on neuronal synaptic plasticity in the motor cortex following cerebral ischemia were published in three issues. We hope that our readers find these papers useful to their research.展开更多
Acupuncture at acupoints Baihui(GV20)and Dazhui(GV14)has been shown to promote functional recovery after stroke.However,the contribution of the contralateral primary sensory cortex(S1)to recovery remains unclear.In th...Acupuncture at acupoints Baihui(GV20)and Dazhui(GV14)has been shown to promote functional recovery after stroke.However,the contribution of the contralateral primary sensory cortex(S1)to recovery remains unclear.In this study,unilateral local ischemic infarction of the primary motor cortex(M1)was induced by photothrombosis in a mouse model.Electroacupuncture(EA)was subsequently performed at acupoints GV20 and GV14 and neuronal activity and functional connectivity of contralateral S1 and M1 were detected using in vivo and in vitro electrophysiological recording techniques.Our results showed that blood perfusion and neuronal interaction between contralateral M1 and S1 is impaired after unilateral M1 infarction.Intrinsic neuronal excitability and activity were also disturbed,which was rescued by EA.Furthermore,the effectiveness of EA treatment was inhibited after virus-mediated neuronal ablation of the contralateral S1.We conclude that neuronal activity of the contralateral S1 is important for EA-mediated recovery after focal M1 infarction.Our study provides insight into how the S1-M1 circuit might be involved in the mechanism of EA treatment of unilateral cerebral infarction.The animal experiments were approved by the Committee for Care and Use of Research Animals of Guangzhou University of Chinese Medicine(approval No.20200407009)April 7,2020.展开更多
Neural degeneration and regeneration are important topics in neurological diseases. There are limited options for therapeutic interventions in neurological diseases that provide simultaneous spatial and temporal contr...Neural degeneration and regeneration are important topics in neurological diseases. There are limited options for therapeutic interventions in neurological diseases that provide simultaneous spatial and temporal control of neurons. This drawback increases side effects due to non-specific targeting. Optogenetics is a technology that allows precise spatial and temporal control of cells. Therefore, this technique has high potential as a therapeutic strategy for neurological diseases. Even though the application of optogenetics in understanding brain functional organization and complex behaviour states have been elaborated, reviews of its therapeutic potential especially in neurodegeneration and regeneration are still limited. This short review presents representative work in optogenetics in disease models such as spinal cord injury, multiple sclerosis, epilepsy, Alzheimer＇s disease and Parkinson＇s disease. It is aimed to provide a broader perspective on optogenetic therapeutic potential in neurodegeneration and neural regeneration.展开更多
Objective Formaldehyde at high concentrations is a contributor to air pollution. It is also an endogenous metabolic product in cells, and when beyond physiological concentrations, has pathological effects on neurons. ...Objective Formaldehyde at high concentrations is a contributor to air pollution. It is also an endogenous metabolic product in cells, and when beyond physiological concentrations, has pathological effects on neurons. Formaldehyde induces mis-folding and aggregation of neuronal tau protein, hippocampal neuronal apoptosis, cognitive impairment and loss of memory functions, as well as excitation of peripheral nociceptive neurons in cancer pain models. Intracellular calcium （[Ca2＋]i） is an important intracellular messenger, and plays a key role in many pathological processes. The present study aimed to investigate the effect of formaldehyde on [Ca2＋]i and the possible involvement of N-methyl-D-aspartate receptors （NMDARs） and T-type Ca2＋ channels on the cell membrane. Methods Using primary cultured hippocampal neurons as a model, changes of [Ca2＋]i in the presence of formaldehyde at a low concentration were detected by confocal laser scanning microscopy. Results Formaldehyde at 1 mmol/L approximately doubled [Ca2＋]i. （2R）-amino-5-phosphonopentanoate （AP5, 25 μmol/L, an NMDAR antagonist） and mibefradil （MIB, 1 μmol/L, a T-type Ca2＋ channel blocker）, given 5 min after formaldehyde perfusion, each partly inhibited the formaldehyde-induced increase of [Ca：＋]i, and this inhibitory effect was reinforced by combined application of AP5 and MIB. When applied 3 min before formaldehyde perfusion, AP5 （even at 50μmol/L） did not inhibit the formaldehyde-induced increase of [Ca2＋]i, but MIB （1 μmol/L） significantly inhibited this increase by 70%. Conclusion These results suggest that formaldehyde at a low concentration increases [Ca2＋]i in cultured hippocampal neurons; NMDARs and T-type Ca2＋ channels may be involved in this process.展开更多
Bilateral arm raising movements have been used in brain rehabilitation for a long time. However, no study has been reported on the effect of these movements on the cerebral cortex. In this study, using functional near...Bilateral arm raising movements have been used in brain rehabilitation for a long time. However, no study has been reported on the effect of these movements on the cerebral cortex. In this study, using functional near infrared spectroscopy（f NIRS）, we attempted to investigate cortical activation generated during bilateral arm raising movements. Ten normal subjects were recruited for this study. f NIRS was performed using an f NIRS system with 49 channels. Bilateral arm raising movements were performed in sitting position at the rate of 0.5 Hz. We measured values of oxyhemoglobin and total hemoglobin in five regions of interest： the primary sensorimotor cortex, premotor cortex, supplementary motor area, prefrontal cortex, and posterior parietal cortex. During performance of bilateral arm raising movements, oxyhemoglobin and total hemoglobin values in the primary sensorimotor cortex, premotor cortex, supplementary motor area, and prefrontal cortex were similar, but higher in these regions than those in the prefrontal cortex. We observed activation of the arm somatotopic areas of the primary sensorimotor cortex and premotor cortex in both hemispheres during bilateral arm raising movements. According to this result, bilateral arm raising movements appeared to induce large-scale neuronal activation and therefore arm raising movements would be good exercise for recovery of brain functions.展开更多
Circadian rhythm protects neurons：Although the master clock entrains the whole body rhythm,peripheral tissues also express core clock transcription factors Clock and Bmal1,which regulate expression of clock genes inc...Circadian rhythm protects neurons：Although the master clock entrains the whole body rhythm,peripheral tissues also express core clock transcription factors Clock and Bmal1,which regulate expression of clock genes including Period（Per）and Cryptochrome（Cry）proteins.Complexes of Per and Cry proteins repress Bmal1-and Clock-mediated transcription forming a negative feedback loop,which regulates nearly a 24 hours self-sustained rhythm including energy metabolism.展开更多
The problem of global robust asymptotical stability for a class of Takagi-Sugeno fuzzy neural networks（TSFNN） with discontinuous activation functions and time delays is investigated by using Lyapunov stability theor...The problem of global robust asymptotical stability for a class of Takagi-Sugeno fuzzy neural networks（TSFNN） with discontinuous activation functions and time delays is investigated by using Lyapunov stability theory.Based on linear matrix inequalities（LMIs）,we originally propose robust fuzzy control to guarantee the global robust asymptotical stability of TSFNNs.Compared with the existing literature,this paper removes the assumptions on the neuron activations such as Lipschitz conditions,bounded,monotonic increasing property or the right-limit value is bigger than the left one at the discontinuous point.Thus,the results are more general and wider.Finally,two numerical examples are given to show the effectiveness of the proposed stability results.展开更多
γ-amidobutyric acid (GABA) is a major inhibitory neurotransmitter in the central nervous system and mediates fast synaptic inhibition through GABAA and GABAC
Comorbid anxiety in chronic pain is clinically common,with a comorbidity rate of over 50%.The main treatments are based on pharmacological,interventional,and implantable approaches,which have limited efficacy and carr...Comorbid anxiety in chronic pain is clinically common,with a comorbidity rate of over 50%.The main treatments are based on pharmacological,interventional,and implantable approaches,which have limited efficacy and carry a risk of side effects.Here,we report a terahertz(THz,1012 Hz)wave stimulation(THS)technique,which exerts nonthermal,long-term modulatory effects on neuronal activity by reducing the binding between nano-sized glutamate molecules and GluA2,leading to the relief of pain and comorbid anxiety-like behaviors in mice.In mice with co-occurring anxiety and chronic pain induced by complete Freund’s adjuvant(CFA)injection,hyperactivity was observed in glutamatergic neurons in the anterior cingulate cortex(ACCGlu).Using whole-cell recording in ACC slices,we demonstrated that THS(34 THz)effectively inhibited the excitability of ACCGlu.Moreover,molecular dynamics simulations showed that THS reduced the number of hydrogen bonds bound between glutamate molecules and GluA2.Furthermore,THS target to the ACC in CFA-treatment mice suppressed ACCGlu hyperactivity and,as a result,alleviated pain and anxiety-like behaviors.Consistently,inhibition of ACCGlu hyperactivity by chemogenetics mimics THS-induced antinociceptive and antianxiety behavior.Together,our study provides evidence for THS as an intervention technique for modulating neuronal activity and a viable clinical treatment strategy for pain and comorbid anxiety.展开更多
Dear Editor,Developing a rapid,controllable method for manipulat-ing physiological functions has significant potential for clinical therapeutics and basic research.Optogenetics has provided optical control of neuronal...Dear Editor,Developing a rapid,controllable method for manipulat-ing physiological functions has significant potential for clinical therapeutics and basic research.Optogenetics has provided optical control of neuronal activity at the millisecond time scale(Bernstein and Boyden,2011;Carter et al.,2010;Madisen et al.,2012).展开更多
Patients with disorders of consciousness suffer from severe impairments in arousal and awareness alongside anomalous brain connections and aberrant neuronal activities.The thalamus,a crucial hub in the brain connectom...Patients with disorders of consciousness suffer from severe impairments in arousal and awareness alongside anomalous brain connections and aberrant neuronal activities.The thalamus,a crucial hub in the brain connectome,has been empirically inferred to maintain consciousness and wakefulness.Here,we investigated thalamic spiking,brain connectivity,consciousness states,and recovery outcomes following deep brain stimulation in 29 patients.Our study reveals that thalamic neuronal activity serves as a marker of consciousness state.Patients diagnosed with vegetative state/unresponsive wakefulness syndrome exhibited less-active neurons,with longer and more variable burst discharges,than those in a minimally conscious state.Furthermore,neuronal profiles in the intralaminar thalamus,the direct stimulation site,predicted whether electrostimulation here improved recovery.Stronger tonic firing was correlated with enhanced thalamocortical connectivity and better recovery outcomes in patients.These findings suggest that thalamic spiking signatures,including singleneuron burst discharge and tonic firing,selectively indicate the representation and alteration of consciousness.展开更多
基金supported by the National Natural Science Foundation of China (31571104 and 81501149)the Science and Technological Project of Shandong Province of China (2016GSF201058)
文摘Restraint water-immersion stress(RWIS), a compound stress model, has been widely used to induce acute gastric ulceration in rats. A wealth of evidence suggests that the central nucleus of the amygdala(CEA) is a focal region for mediating the biological response to stress. Different stressors induce distinct alterations of neuronal activity in the CEA; however, few studies have reported the characteristics of CEA neuronal activity induced by RWIS. Therefore, we explored this issue using immunohistochemistry and in vivo extracellular single-unit recording. Our results showed that RWIS and restraint stress(RS) differentially changed the c-Fos expression and firing properties of neurons in the medial CEA. In addition,RWIS, but not RS, induced the activation of corticotropinreleasing hormone neurons in the CEA. These findings suggested that specific neuronal activation in the CEA is involved in the formation of RWIS-induced gastric ulcers.This study also provides a possible theoretical explanation for the different gastric dysfunctions induced by different stressors.
基金supported by the National Natural Science Foundation of China(No.61074131,91132722)the Doctoral Fund of the Ministry of Education of China(20101202110007).
文摘Neuronal ensemble activity codes working memory.In this work,we developed a neuronal ensemble sparse coding method,which can effectively reduce the dimension of the neuronal activity and express neural coding.Multichannel spike trains were recorded in rat prefrontal cortex during a work memory task in Y-maze.As discretesignals,spikes were transferred into cont inuous signals by estinating entropy.Then the normalized continuous signals were decomposed via non-negative sparse met hod.The non-negative components were extracted to reconstruct a low-dimensional ensemble,while none of the feature components were missed.The results showed that,for well-trained rats,neuronal ensemble activities in the prefrontal cortex changed dynamically during the.working memory task.And the neuronal ensemble is more explicit via using non-negative sparse coding.Our results indicate that the neuronal ensemblesparse coding method can effectively reduce the dimnension of neuronal activity and it is a useful tool to express neural coding.
基金supported by the National Natural Science Foundation of China,Nos.32371065(to CL)and 32170950(to LY)the Natural Science Foundation of the Guangdong Province,No.2023A1515010899(to CL)the Science and Technology Projects in Guangzhou,Nos.2023A4J0578 and 2024A03J0180(to CW)。
文摘Neuronal activity,synaptic transmission,and molecular changes in the basolateral amygdala play critical roles in fear memory.Cylindromatosis(CYLD)is a deubiquitinase that negatively regulates the nuclear factor kappa-B pathway.CYLD is well studied in non-neuronal cells,yet underinvestigated in the brain,where it is highly expressed.Emerging studies have shown involvement of CYLD in the remodeling of glutamatergic synapses,neuroinflammation,fear memory,and anxiety-and autism-like behaviors.However,the precise role of CYLD in glutamatergic neurons is largely unknown.Here,we first proposed involvement of CYLD in cued fear expression.We next constructed transgenic model mice with specific deletion of Cyld from glutamatergic neurons.Our results show that glutamatergic CYLD deficiency exaggerated the expression of cued fear in only male mice.Further,loss of CYLD in glutamatergic neurons resulted in enhanced neuronal activation,impaired excitatory synaptic transmission,and altered levels of glutamate receptors accompanied by over-activation of microglia in the basolateral amygdala of male mice.Altogether,our study suggests a critical role of glutamatergic CYLD in maintaining normal neuronal,synaptic,and microglial activation.This may contribute,at least in part,to cued fear expression.
文摘The complex morphological,anatomical,physiological,and chemical mechanisms within the aging brain have been the hot topic of research for centuries.The aging process alters the brain structure that affects functions and cognitions,but the worsening of such processes contributes to the pathogenesis of neurodegenerative disorders,such as Alzheimer's disease.Beyond these observable,mild morphological shifts,significant functional modifications in neurotransmission and neuronal activity critically influence the aging brain.Understanding these changes is important for maintaining cognitive health,especially given the increasing prevalence of age-related conditions that affect cognition.This review aims to explore the age-induced changes in brain plasticity and molecular processes,differentiating normal aging from the pathogenesis of Alzheimer's disease,thereby providing insights into predicting the risk of dementia,particularly Alzheimer's disease.
基金supported by the National Natural Science Foundation of China(82071191,82001129)Natural Science Foundation of Sichuan Province(2022NSFSC1509)+1 种基金National Clinical Research Center for Geriatrics of West China Hospital(Z2021LC001)West China Hospital 1.3.5 Project for Disciplines of Excellence(ZYYC20009)。
文摘Delirium is a severe acute neuropsychiatric syndrome that commonly occurs in the elderly and is considered an independent risk factor for later dementia.However,given its inherent complexity,few animal models of delirium have been established and the mechanism underlying the onset of delirium remains elusive.Here,we conducted a comparison of three mouse models of delirium induced by clinically relevant risk factors,including anesthesia with surgery(AS),systemic inflammation,and neurotransmission modulation.We found that both bacterial lipopolysaccharide(LPS)and cholinergic receptor antagonist scopolamine(Scop)induction reduced neuronal activities in the delirium-related brain network,with the latter presenting a similar pattern of reduction as found in delirium patients.Consistently,Scop injection resulted in reversible cognitive impairment with hyperactive behavior.No loss of cholinergic neurons was found with treatment,but hippocampal synaptic functions were affected.These findings provide further clues regarding the mechanism underlying delirium onset and demonstrate the successful application of the Scop injection model in mimicking delirium-like phenotypes in mice.
基金supported by grants from the National Natural Science Foundation of China(31970953,81930032,and 81760505)the Natural Science Foundation of Jiangxi Province,China(20192ACB21024,20192ACB20023,20181ACG70003,and 20192BCB23008).
文摘Chronic stress leads to many psychiatric disorders,including social and anxiety disorders that are associated with over-activation of neurons in the basolateral amygdala(BLA).However,not all individuals develop psychiatric diseases,many showing considerable resilience against stress exposure.Whether BLA neuronal activity is involved in regulating an individual’s vulnerability to stress remains elusive.In this study,using a mouse model of chronic social defeat stress(CSDS),we divided the mice into susceptible and resilient subgroups based on their social interaction behavior.Using in vivo fiber photometry and in vitro patch-clamp recording,we showed that CSDS persistently(after 20 days of recovery from stress)increased BLA neuronal activity in all the mice regardless of their susceptible or resilient nature,although impaired social interaction behavior was only observed in susceptible mice.Increased anxiety-like behavior,on the other hand,was evident in both groups.Notably,the CSDS-induced increase of BLA neuronal activity correlated well with the heightened anxiety-like but not the social avoidance behavior in mice.These findings provide new insight to our understanding of the role of neuronal activity in the amygdala in mediating stress-related psychiatric disorders.
文摘As a second messenger in signal transduction,calcium ion plays a very important role in neuronal information processing and integrating.Limited by the imaging technique,it is difficult to simultaneously perform deep tissue imaging and measure intracellular free calcium concentration([Ca^(2+)]i)in different compartments of neurons in brain slice noncollinearly.By means of random access two-photon microscopy,which provides high optical penetration into tissues and low photo damage,we successfully measured[Ca^(2+)]i of different parts of pyramidal neurons in neocortical layer V in rat brain slices with high spatial and temporal resolution.Combining the patch clamp technique,we stimulated the soma with depolarizing current and explored the dynamics of calcium in pyramidal neurons.
基金supported by the National Natural Science Foundation of China,No.81171852
文摘Disorder of consciousness （DOC） is one of the most serious sequelae of brain injury, and is challenging for neurologists and rehabilitation special- ists to manage because of its refractory nature （Whyte et al., 2013）. Acu- puncture is a traditional Chinese medicine technique that is often used to help improve the level of consciousness in patients with DOC. However, the responses to stimulation of acupoints in patients with DOC are not fully understood.
文摘Totally three articles focusing on Schisandra N-butanol extract effects on hippocampal CA1 synaptic morphology and plasticity in ovarectomized mice, as well as catalpol and GBE50 effects on neuronal synaptic plasticity in the motor cortex following cerebral ischemia were published in three issues. We hope that our readers find these papers useful to their research.
基金Guangzhou University of Chinese Medicine and by grants from General Program of the National Natural Science Foundation of China(No.81774406,to NGX)Youth Program of the National Natural Science Foundation of China(No.82004469,to LLY)+1 种基金Fellowship of China postdoctoral Science Foundation(No.2020M672601,to LLY)Opening Operation Program of Key Laboratory of Acupuncture and Moxibustion of Traditional Chinese Medicine in Guangdong(No.2017B030314143,to NGX).
文摘Acupuncture at acupoints Baihui(GV20)and Dazhui(GV14)has been shown to promote functional recovery after stroke.However,the contribution of the contralateral primary sensory cortex(S1)to recovery remains unclear.In this study,unilateral local ischemic infarction of the primary motor cortex(M1)was induced by photothrombosis in a mouse model.Electroacupuncture(EA)was subsequently performed at acupoints GV20 and GV14 and neuronal activity and functional connectivity of contralateral S1 and M1 were detected using in vivo and in vitro electrophysiological recording techniques.Our results showed that blood perfusion and neuronal interaction between contralateral M1 and S1 is impaired after unilateral M1 infarction.Intrinsic neuronal excitability and activity were also disturbed,which was rescued by EA.Furthermore,the effectiveness of EA treatment was inhibited after virus-mediated neuronal ablation of the contralateral S1.We conclude that neuronal activity of the contralateral S1 is important for EA-mediated recovery after focal M1 infarction.Our study provides insight into how the S1-M1 circuit might be involved in the mechanism of EA treatment of unilateral cerebral infarction.The animal experiments were approved by the Committee for Care and Use of Research Animals of Guangzhou University of Chinese Medicine(approval No.20200407009)April 7,2020.
基金supported in part by NIH NS059622,NS073636,DOD CDMRP W81XWH-12-1-0562,Merit Review Award I01 BX002356 from the U.SDepartment of Veterans Affairs,Craig H Neilsen Foundation 296749+1 种基金Indiana Spinal Cord and Brain Injury Research Foundation(ISCBIRF)019919Mari Hulman George Endowment Funds
文摘Neural degeneration and regeneration are important topics in neurological diseases. There are limited options for therapeutic interventions in neurological diseases that provide simultaneous spatial and temporal control of neurons. This drawback increases side effects due to non-specific targeting. Optogenetics is a technology that allows precise spatial and temporal control of cells. Therefore, this technique has high potential as a therapeutic strategy for neurological diseases. Even though the application of optogenetics in understanding brain functional organization and complex behaviour states have been elaborated, reviews of its therapeutic potential especially in neurodegeneration and regeneration are still limited. This short review presents representative work in optogenetics in disease models such as spinal cord injury, multiple sclerosis, epilepsy, Alzheimer＇s disease and Parkinson＇s disease. It is aimed to provide a broader perspective on optogenetic therapeutic potential in neurodegeneration and neural regeneration.
基金supported by grants from the National Natural Science Foundation of China (81171042,81070893 and 81221002)the Beijing Outstanding Ph.D.Program Mentor Grantthe Specialized Research Fund for Doctoral Programs of Higher Education, China(20110001110058)
文摘Objective Formaldehyde at high concentrations is a contributor to air pollution. It is also an endogenous metabolic product in cells, and when beyond physiological concentrations, has pathological effects on neurons. Formaldehyde induces mis-folding and aggregation of neuronal tau protein, hippocampal neuronal apoptosis, cognitive impairment and loss of memory functions, as well as excitation of peripheral nociceptive neurons in cancer pain models. Intracellular calcium （[Ca2＋]i） is an important intracellular messenger, and plays a key role in many pathological processes. The present study aimed to investigate the effect of formaldehyde on [Ca2＋]i and the possible involvement of N-methyl-D-aspartate receptors （NMDARs） and T-type Ca2＋ channels on the cell membrane. Methods Using primary cultured hippocampal neurons as a model, changes of [Ca2＋]i in the presence of formaldehyde at a low concentration were detected by confocal laser scanning microscopy. Results Formaldehyde at 1 mmol/L approximately doubled [Ca2＋]i. （2R）-amino-5-phosphonopentanoate （AP5, 25 μmol/L, an NMDAR antagonist） and mibefradil （MIB, 1 μmol/L, a T-type Ca2＋ channel blocker）, given 5 min after formaldehyde perfusion, each partly inhibited the formaldehyde-induced increase of [Ca：＋]i, and this inhibitory effect was reinforced by combined application of AP5 and MIB. When applied 3 min before formaldehyde perfusion, AP5 （even at 50μmol/L） did not inhibit the formaldehyde-induced increase of [Ca2＋]i, but MIB （1 μmol/L） significantly inhibited this increase by 70%. Conclusion These results suggest that formaldehyde at a low concentration increases [Ca2＋]i in cultured hippocampal neurons; NMDARs and T-type Ca2＋ channels may be involved in this process.
基金supported by the DGIST R&D Program of the Ministry of Science,ICT and Future Planning,No.16-BD-0401
文摘Bilateral arm raising movements have been used in brain rehabilitation for a long time. However, no study has been reported on the effect of these movements on the cerebral cortex. In this study, using functional near infrared spectroscopy（f NIRS）, we attempted to investigate cortical activation generated during bilateral arm raising movements. Ten normal subjects were recruited for this study. f NIRS was performed using an f NIRS system with 49 channels. Bilateral arm raising movements were performed in sitting position at the rate of 0.5 Hz. We measured values of oxyhemoglobin and total hemoglobin in five regions of interest： the primary sensorimotor cortex, premotor cortex, supplementary motor area, prefrontal cortex, and posterior parietal cortex. During performance of bilateral arm raising movements, oxyhemoglobin and total hemoglobin values in the primary sensorimotor cortex, premotor cortex, supplementary motor area, and prefrontal cortex were similar, but higher in these regions than those in the prefrontal cortex. We observed activation of the arm somatotopic areas of the primary sensorimotor cortex and premotor cortex in both hemispheres during bilateral arm raising movements. According to this result, bilateral arm raising movements appeared to induce large-scale neuronal activation and therefore arm raising movements would be good exercise for recovery of brain functions.
基金support of JSPS KAKENHI Grant Number 21500386 (TI)British Heart Foundation (GEM, FS/15/31298 FS/16/67/32548)
文摘Circadian rhythm protects neurons：Although the master clock entrains the whole body rhythm,peripheral tissues also express core clock transcription factors Clock and Bmal1,which regulate expression of clock genes including Period（Per）and Cryptochrome（Cry）proteins.Complexes of Per and Cry proteins repress Bmal1-and Clock-mediated transcription forming a negative feedback loop,which regulates nearly a 24 hours self-sustained rhythm including energy metabolism.
基金supported by the National Natural Science Foundation of China(6077504760835004)+2 种基金the National High Technology Research and Development Program of China(863 Program)(2007AA04Z244 2008AA04Z214)the Graduate Innovation Fundation of Hunan Province(CX2010B132)
文摘The problem of global robust asymptotical stability for a class of Takagi-Sugeno fuzzy neural networks（TSFNN） with discontinuous activation functions and time delays is investigated by using Lyapunov stability theory.Based on linear matrix inequalities（LMIs）,we originally propose robust fuzzy control to guarantee the global robust asymptotical stability of TSFNNs.Compared with the existing literature,this paper removes the assumptions on the neuron activations such as Lipschitz conditions,bounded,monotonic increasing property or the right-limit value is bigger than the left one at the discontinuous point.Thus,the results are more general and wider.Finally,two numerical examples are given to show the effectiveness of the proposed stability results.
文摘γ-amidobutyric acid (GABA) is a major inhibitory neurotransmitter in the central nervous system and mediates fast synaptic inhibition through GABAA and GABAC
基金supported by the National Natural Science Foundation of China(grants T2241002 and 12225511)support from the Xplore Prize No.2020-1023by China Academy of Traditional Chinese Medicine Science and Technology Innovation Project(grant:CI2023C017YL).
文摘Comorbid anxiety in chronic pain is clinically common,with a comorbidity rate of over 50%.The main treatments are based on pharmacological,interventional,and implantable approaches,which have limited efficacy and carry a risk of side effects.Here,we report a terahertz(THz,1012 Hz)wave stimulation(THS)technique,which exerts nonthermal,long-term modulatory effects on neuronal activity by reducing the binding between nano-sized glutamate molecules and GluA2,leading to the relief of pain and comorbid anxiety-like behaviors in mice.In mice with co-occurring anxiety and chronic pain induced by complete Freund’s adjuvant(CFA)injection,hyperactivity was observed in glutamatergic neurons in the anterior cingulate cortex(ACCGlu).Using whole-cell recording in ACC slices,we demonstrated that THS(34 THz)effectively inhibited the excitability of ACCGlu.Moreover,molecular dynamics simulations showed that THS reduced the number of hydrogen bonds bound between glutamate molecules and GluA2.Furthermore,THS target to the ACC in CFA-treatment mice suppressed ACCGlu hyperactivity and,as a result,alleviated pain and anxiety-like behaviors.Consistently,inhibition of ACCGlu hyperactivity by chemogenetics mimics THS-induced antinociceptive and antianxiety behavior.Together,our study provides evidence for THS as an intervention technique for modulating neuronal activity and a viable clinical treatment strategy for pain and comorbid anxiety.
基金supported by the National Natural Science Foundation of China(Original Exploration Program,32250018 and the National Basic Research Program of China,81971060).
文摘Dear Editor,Developing a rapid,controllable method for manipulat-ing physiological functions has significant potential for clinical therapeutics and basic research.Optogenetics has provided optical control of neuronal activity at the millisecond time scale(Bernstein and Boyden,2011;Carter et al.,2010;Madisen et al.,2012).
基金supported by funding fromBeijingNatural Science Foundation grant Z210009National Science and Technology Innovation 2030 Major Projects,STI2030-Major Projects grant 2022ZD0204800+4 种基金National Natural Science Foundation of China grants 32070987 and 31722025Chinese Academy of Sciences Key Program of Frontier Sciences grant QYZDB-SSW-SMC019supported by funding from National Key R&D Program of China grant 2022YFB4700100Strategic Priority Research Program of Chinese Academy of Sciences XDB37030303funded as a chairholder from the Canada Excellence Research Chair in Neuroplasticity,as research director at the Belgian National Fund for Scientific Research,by the European Foundation of Biomedical Research,by the Foundation for Research and Rehabilitation of Neurodegenerative Diseases,and by National Natural Science Foundation of China 81920108023.
文摘Patients with disorders of consciousness suffer from severe impairments in arousal and awareness alongside anomalous brain connections and aberrant neuronal activities.The thalamus,a crucial hub in the brain connectome,has been empirically inferred to maintain consciousness and wakefulness.Here,we investigated thalamic spiking,brain connectivity,consciousness states,and recovery outcomes following deep brain stimulation in 29 patients.Our study reveals that thalamic neuronal activity serves as a marker of consciousness state.Patients diagnosed with vegetative state/unresponsive wakefulness syndrome exhibited less-active neurons,with longer and more variable burst discharges,than those in a minimally conscious state.Furthermore,neuronal profiles in the intralaminar thalamus,the direct stimulation site,predicted whether electrostimulation here improved recovery.Stronger tonic firing was correlated with enhanced thalamocortical connectivity and better recovery outcomes in patients.These findings suggest that thalamic spiking signatures,including singleneuron burst discharge and tonic firing,selectively indicate the representation and alteration of consciousness.
