The conventional perception of astrocytes as mere supportive cells within the brain has recently been called into question by empirical evidence, which has revealed their active involvement in regulating brain functio...The conventional perception of astrocytes as mere supportive cells within the brain has recently been called into question by empirical evidence, which has revealed their active involvement in regulating brain function and encoding behaviors associated with emotions.Specifically, astrocytes in the basolateral amygdala have been found to play a role in the modulation of anxiety-like behaviors triggered by chronic stress. Nevertheless, the precise molecular mechanisms by which basolateral amygdala astrocytes regulate chronic stress–induced anxiety-like behaviors remain to be fully elucidated. In this study, we found that in a mouse model of anxiety triggered by unpredictable chronic mild stress, the expression of excitatory amino acid transporter 2 was upregulated in the basolateral amygdala. Interestingly, our findings indicate that the targeted knockdown of excitatory amino acid transporter 2 specifically within the basolateral amygdala astrocytes was able to rescue the anxiety-like behavior in mice subjected to stress. Furthermore, we found that the overexpression of excitatory amino acid transporter 2 in the basolateral amygdala, whether achieved through intracranial administration of excitatory amino acid transporter 2agonists or through injection of excitatory amino acid transporter 2-overexpressing viruses with GfaABC1D promoters, evoked anxiety-like behavior in mice. Our single-nucleus RNA sequencing analysis further confirmed that chronic stress induced an upregulation of excitatory amino acid transporter 2 specifically in astrocytes in the basolateral amygdala. Moreover, through in vivo calcium signal recordings, we found that the frequency of calcium activity in the basolateral amygdala of mice subjected to chronic stress was higher compared with normal mice.After knocking down the expression of excitatory amino acid transporter 2 in the basolateral amygdala, the frequency of calcium activity was not significantly increased, and anxiety-like behavior was obviously mitigated. Additionally, administration of an excitatory amino acid transporter 2 inhibitor in the basolateral amygdala yielded a notable reduction in anxiety level among mice subjected to stress. These results suggest that basolateral amygdala astrocytic excitatory amino acid transporter 2 plays a role in in the regulation of unpredictable chronic mild stress-induced anxiety-like behavior by impacting the activity of local glutamatergic neurons, and targeting excitatory amino acid transporter 2 in the basolateral amygdala holds therapeutic promise for addressing anxiety disorders.展开更多
Bromodomain and plant homeodomain(PHD)finger containing protein 1(Brpf1)is an activator and scaffold protein of a multiunit complex that includes other components involving lysine acetyltransferase(KAT)6A/6B/7.Brpf1,K...Bromodomain and plant homeodomain(PHD)finger containing protein 1(Brpf1)is an activator and scaffold protein of a multiunit complex that includes other components involving lysine acetyltransferase(KAT)6A/6B/7.Brpf1,KAT6A,and KAT6B mutations were identified as the causal genes of neurodevelopmental disorders leading to intellectual disability.Our previous work revealed strong and specific expression of Brpf1 in both the postnatal and adult forebrain,especially the hippocampus,which has essential roles in learning and memory.Here,we hypothesized that Brpf1 plays critical roles in the function of forebrain excitatory neurons,and that its deficiency leads to learning and memory deficits.To test this,we knocked out Brpf1 in forebrain excitatory neurons using CaMKIIa-Cre.We found that Brpf1 deficiency reduced the frequency of miniature excitatory postsynaptic currents and downregulated the expression of genes Pcdhgb1,Slc16a7,Robo3,and Rho,which are related to neural development,synapse function,and memory,thereby damaging spatial and fear memory in mice.These findings help explain the mechanisms of intellectual impairment in patients with BRPF1 mutation.展开更多
BZ]Dendro dendritic and dendro somatic projections are common between spinal motoneurons. We attempted to clarify whether there are functional connections through these projections. Methods. Motoneurons were antidromi...BZ]Dendro dendritic and dendro somatic projections are common between spinal motoneurons. We attempted to clarify whether there are functional connections through these projections. Methods. Motoneurons were antidromically stimulated by the muscle nerve and recorded intracellularly to examine the direct interaction between them, after the related dorsal roots had been cut. Results. Excitatory connections, demonstrated by depolarizing potentials in response to muscle nerve stimulation, were found between motoneurons innervating the same muscle or synergistic muscles, but never between motoneurons innervating antagonistic muscles. These potentials were finely graded in response to a series of increasing stimuli and resistant to high frequency (50Hz) stimulation. Conclusions.These results indicate that excitatory connections, with certain specificity of spatial and temporal distribution, occur in the spinal motoneurons. It is also suggested that electrical coupling should be involved in these connections and this mechanism should improve the excitability of the motoneurons in the same column.展开更多
Ras-related C3 botulinum toxin substrate 1(Racl),a member of the Rho GTPase family which plays important roles in dendritic spine morphology and plasticity,is a key regulator of cytoskeletal reorganization in dendrite...Ras-related C3 botulinum toxin substrate 1(Racl),a member of the Rho GTPase family which plays important roles in dendritic spine morphology and plasticity,is a key regulator of cytoskeletal reorganization in dendrites and spines.Here,we investigated whether and how Racl modulates synaptic transmission in mouse retinal ganglion cells(RGCs)using selective conditional knockout of Racl(Racl-cKO).Racl-cKO significantly reduced the frequency of AMPA receptor-mediated miniature excitatory postsynaptic currents,while glycine/GABA_A receptor-mediated miniature inhibitory postsynaptic currents were not affected.Although the total GluA1 protein level was increased in Racl-cKO mice,its expression in the membrane component was unchanged.RaclcKO did not affect spine-like branch density in single dendrites,but significantly reduced the dendritic complexity,which resulted in a decrease in the total number of dendritic spine-like branches.These results suggest that Racl selectively affects excitatory synaptic transmission in RGCs by modulating dendritic complexity.展开更多
Neurons in the primary auditory area(AUDp)innervate multiple brain regions with long-range projections while receiving informative inputs for diverse functions.However,the brain-wide connections of these neurons have ...Neurons in the primary auditory area(AUDp)innervate multiple brain regions with long-range projections while receiving informative inputs for diverse functions.However,the brain-wide connections of these neurons have not been comprehensively investigated.Here,we simultaneously applied virus-based anterograde and retrograde tracing,labeled the connections of excitatory and inhibitory neurons in the mouse AUDp,and acquired whole-brain information using a dual-channel fuorescence micro-optical sectioning tomography system.Quantified results showed that the two types of neurons received inputs with similar patterns but sent heterogeneous projections to downstream regions.In the isocortex,functionally different areas consistently sent feedback-dominated projections to these neurons,with concomitant laterallydominated projections from the sensory and limbic cortices to inhibitory neurons.In subcortical regions,the dorsal and medial parts of the non-lemniscal auditory thalamus(AT)were reciprocally connected to the AUDp,while the ventral part contained the most fibers of passage from the excitatory neurons and barely sent projections back,indicating the regional heterogeneity of the AUDp-AT circuit.Our results reveal details of the whole-brain network and provide new insights for further physiological and functional studies of the AUDp.展开更多
Selective cerebral deep hypothermia and blood flow occlusion can enhance brain tolerance to ischemia and hypoxia and reduce cardiopulmonary complications in monkeys. Excitotoxicity induced by the release of a large am...Selective cerebral deep hypothermia and blood flow occlusion can enhance brain tolerance to ischemia and hypoxia and reduce cardiopulmonary complications in monkeys. Excitotoxicity induced by the release of a large amount of excitatory amino acids after cerebral ischemia is the major mechanism underlying ischemic brain injury and nerve cell death. In the present study, we used selective cerebral deep hypothermia and blood flow occlusion to block the bilateral common carotid arteries and/or bilateral vertebral arteries in rhesus monkey, followed by reperfusion using Ringer＇s solution at 4~C. Microdialysis and transmission electron microscope results showed that selective cerebral deep hypothermia and blood flow occlusion inhibited the release of glutamic acid into the extracellular fluid in the brain frontal lobe and relieved pathological injury in terms of the ultrastructure of brain tissues after severe cerebral ischemia. These findings indicate that cerebral deep hypothermia and blood flow occlusion can inhibit cytotoxic effects and attenuate ischemic/ hypoxic brain injury through decreasing the release of excitatory amino acids, such as glutamic acid.展开更多
Aim Prenatal stress （PS） can lead to abnormal behavior of offspring and increase the incidence of mental illness. Previous researches have shown that levels of glutamate and its receptor expression are closely relat...Aim Prenatal stress （PS） can lead to abnormal behavior of offspring and increase the incidence of mental illness. Previous researches have shown that levels of glutamate and its receptor expression are closely relat- ed to the occurrence of this phenomenon. Furthermore, recent study has demonstrated that the expression levels of excitatory amino acid transporters 2 （EAAT2） in different brain regions of 1 month PS offspring rats have changed. Methods The SD pregnant rats were used restraint stress to imitate PS from gestation 14 -~ 19 days. Offspring rats were weaned 21 days after birth. The expression of EAAT2 of hippocampus was observed by Western blot. Results The expression of EAAT2 of 1 month PS offspring rats was significantly decreased in comparison to control group. However, the expression of EAAT2 of 2 month PS offspring rats was significantly increased in comparison to 1 month PS offspring rats. Conclusion These phenomena have illustrated that the expression of EAAT2 of PS off- spring rats could show time dependence or reversibility. The expression of EAAT2 may play an important role in the development of mental illness of offspring rats influenced by PS.展开更多
In traditional viewpoint,excitatory modulation always promotes neural firing activities.On contrary,the negative responses of complex bursting behaviors to excitatory self-feedback mediated by autapse with time delay ...In traditional viewpoint,excitatory modulation always promotes neural firing activities.On contrary,the negative responses of complex bursting behaviors to excitatory self-feedback mediated by autapse with time delay are acquired in the present paper.Two representative bursting patterns which are identified respectively to be“Fold/Big Homoclinic”bursting and“Circle/Fold cycle”bursting with bifurcations are studied.For both burstings,excitatory modulation can induce less spikes per burst for suitable time delay and strength of the self-feedback/autapse,because the modulation can change the initial or termination phases of the burst.For the former bursting composed of quiescent state and burst,the mean firing frequency exhibits increase,due to that the quiescent state becomes much shorter than the burst.However,for the latter bursting pattern with more complex behavior which is depolarization block lying between burst and quiescent state,the firing frequency manifests decrease in a wide range of time delay and strength,because the duration of both depolarization block and quiescent state becomes long.Therefore,the decrease degree of spike number per burst is larger than that of the bursting period,which is the cause for the decrease of firing frequency.Such reduced bursting activity is explained with the relations between the bifurcation points of the fast subsystem and the bursting trajectory.The present paper provides novel examples of paradoxical phenomenon that the excitatory effect induces negative responses,which presents possible novel modulation measures and potential functions of excitatory self-feedback/autapse to reduce bursting activities.展开更多
Zn neural networks, both excitatory and inhibitory cells play important roles in determining the functions of systems. Various dynamical networks have been proposed as artificial neural networks to study the propertie...Zn neural networks, both excitatory and inhibitory cells play important roles in determining the functions of systems. Various dynamical networks have been proposed as artificial neural networks to study the properties of biological systems where the influences of excitatory nodes have been extensively investigated while those of inhibitory nodes have been studied much less. In this paper, we consider a model of oscillatory networks of excitable Boolean maps consisting of both excitatory and inhibitory nodes, focusing on the roles of inhibitory nodes. We find that inhibitory nodes in sparse networks （smM1 average connection degree） play decisive roles in weakening oscillations, and oscillation death occurs after continual weakening of oscillation for sufficiently high inhibitory node density. In the sharp contrast, increasing inhibitory nodes in dense networks may result in the increase of oscillation amplitude and sudden oscillation death at much lower inhibitory node density and the nearly highest excitation activities. Mechanism under these peculiar behaviors of dense networks is explained by the competition of the duplex effects of inhibitory nodes.展开更多
BACKGROUND： Under normal conditions, excitatory amino acids are dynamically balanced with inhibitory amino acids. Excitatory amino acids have been implicated in perinatal brain injury. OBJECTIVE： To investigate diff...BACKGROUND： Under normal conditions, excitatory amino acids are dynamically balanced with inhibitory amino acids. Excitatory amino acids have been implicated in perinatal brain injury. OBJECTIVE： To investigate differences in the levels of the excitatory amino acids glutamic acid and aspartic acid, and the inhibitory amino acid gamma-aminobutyric acid （GABA） in the cerebrospinal fluid （CSF） of children with spastic cerebral palsy or athetotic cerebral palsy. DESIGN, TIME AND SETTING： Case-control exploratory observation of neurotransmitter in patients. The experiment was performed in the Pediatrics Department of the Second Affiliated Hospital of Changsha Medical College, the Cerebral Palsy Center of Xiangtan Affiliated Hospital of South China University and the Pediatrics Department of Xiangya Hospital, between February 2006 and May 2007. PARTICIPANTS： We selected 27 children with cerebral palsy, including 13 with spastic cerebral palsy and 14 with athetotic cerebral palsy. We selected 10 patients who were not affected by any neurological disease as controls. METHODS： Two mL blood-free CSF was harvested between the third and fourth lumbar vertebrae of each patient after anesthesia, and stored at -70℃. One mL CSF was mixed with 10 mg sulfosalicylic acid and placed in ice-bath for 10 minutes, then centrifuged 2 000 g for 10 minutes. The supernatant was collected for amino acid quantitation. MAIN OUTCOME MEASURES： The concentrations of glutamic acid, aspartic acid and GABA in the CSF were determined by high-performance liquid chromatography and fluorometric method. The correlation of glutamic acid, aspartic acid and GABA levels with muscular tension in children with cerebral palsy was analyzed using linear dependence. RESULTS： The concentration of GABA was significantly lower in both spastic cerebral palsy and athetotic cerebral palsy patients than in the control group （P 〈 0.01）. Glutamic acid and aspartic acid were significantly higher in both cerebral palsy groups than in the control group （P 〈 0.05-0.01）. The concentration of GABA was significantly decreased in spastic cerebral palsy patients compared with the athetotic cerebral palsy group （P 〈 0.05）. Muscular tension was positively correlated with the concentration of glutamic acid in spastic cerebral palsy patients （P 〈 0.05） but there was no significant correlation between aspartic acid or GABA and muscular tension （P 〉 0.05）. CONCLUSION： Spastic cerebral palsy and athetotic cerebral palsy patients exhibit an imbalance of excitatory amino acids and inhibitory amino acids in their CSF： an increase in glutamic acid and aspartic acid, and a decrease in GABA. Amino acid levels are different in the CSF in varied types of cerebral palsy.展开更多
Different from the common delayed synchronization(DS)in which response appears after stimulation,anticipated synchronization(AS)in unidirectionally coupled neurons denotes a counterintuitive phenomenon in which respon...Different from the common delayed synchronization(DS)in which response appears after stimulation,anticipated synchronization(AS)in unidirectionally coupled neurons denotes a counterintuitive phenomenon in which response of the receiver neuron appears before stimulation of the sender neuron,showing an interesting function of brain to anticipate the future.The dynamical mechanism for the AS remains unclear due to complex dynamics of inhibitory and excitatory modulations.In this article,the paradoxical roles of excitatory synapse and inhibitory autapse in the formation of AS are acquired.Firstly,in addition to the common roles such that inhibitory modulation delays and excitatory modulation advances spike,paradoxical roles of excitatory stimulation to delay spike via type-II phase response and of inhibitory autapse to advance spike are obtained in suitable parameter regions,extending the dynamics and functions of the excitatory and inhibitory modulations.Secondly,AS is related to the paradoxical roles of the excitatory and inhibitory modulations,presenting deep understandings to the AS.Inhibitory autapse induces spike of the receiver neuron advanced to appear before that of the sender neuron at first,and then excitatory synapse plays a delay role to prevent the spike further advanced,resulting in the AS as the advance and delay effects realize a dynamic balance.Lastly,inhibitory autapse with strong advance,middle advance,and weak advance and delay effects induce phase drift(spike of the receiver neuron advances continuously),AS,and DS,respectively,presenting comprehensive relationships between AS and other behaviors.The results present potential measures to modulate AS related to brain function.展开更多
Excitation and inhibition are at the core of brain function and malfunction.To sustain the activity of neuronal networks over time and space,glutamatergic excitation is balanced by GABAergic inhibition.The equipoise o...Excitation and inhibition are at the core of brain function and malfunction.To sustain the activity of neuronal networks over time and space,glutamatergic excitation is balanced by GABAergic inhibition.The equipoise of excitation and inhibition,known as the excitation/inhibition(E/I)balance,is crucial for proper brain function.The E/I balance is highly dynamic and shifts across different brain states:wakefulness primarily augments excitatory activity,while sleep promotes a decrease in excitation and an increase in inhibition(Bridi et al.,2020).Neuronal activity during various brain states is primarily regulated by neurotransmitters(Schiemann et al.,2015),alongside non-synaptic mechanisms that operate on a slower timescale.The non-synaptic mechanisms are many,with the ionic composition of the extracellular space playing a significant role;altering extracellular ion concentrations affects sleep,arousal,electroencephalogram patterns,and behavioral states(Ding et al.,2016).展开更多
To elucidate the correlation between excitatory amino acids (EAA) and spinal cord injury, we investigat-ed the dynamic changes in excitatory amino acids, aspartate (Asp) and glutamate (Gin ) contents in cerebrospinalf...To elucidate the correlation between excitatory amino acids (EAA) and spinal cord injury, we investigat-ed the dynamic changes in excitatory amino acids, aspartate (Asp) and glutamate (Gin ) contents in cerebrospinalfluid (CSF) of 26 patients with acute spinal cord injury by amino acids autoanalyzer. The results showed that con-tent of glutanlate and aspartate was renlarkably elevated in 24 h after trauma and was related to the seventy of injury. The more severe the spinal cord injured, the more remarkable the content of Asp and Gin in CSF increased.The more pronounced the content of EAA in CSF increased, the worse the patient’s prognosis was. Content of EAA in CSF after spinal cord injury may be an indicator to judge injury extent and prognosis. and provide further support for a potential pathophysiological role of EAA in spinal cord injury.展开更多
Sprague-Dawley rats were subjected to traumatic spinal cord injury using Allen's method. Regional concentrations of excitatory amino acid (EAA) were assessed by high-performance liquid chromatography, and regional...Sprague-Dawley rats were subjected to traumatic spinal cord injury using Allen's method. Regional concentrations of excitatory amino acid (EAA) were assessed by high-performance liquid chromatography, and regional water and ion content were measured by the atomic absorption spectrophotometry at various times after intrathecal administration of different dosage of 3-(2-carboxypiperazin-4-yl)-propyl-1-phosphonic acid (CPP),a specific antagonist of N-methyl-D-aspartame (NMDA) receptor,to rat at 48 h posttrauma.The results showed that concentrations of glutamate and aspartate were elevated rapidly at 15, 30 min and were correlated positively with the severity of injury. In the injured segment there was a significant increase in water, Na+ ,Ca++ content and a decrease in K+ , Mg++. Whereas in CPP treated groups they had a statistically significant return, which was related to the dosage and time of administration. This effect of CPP suggests that ion and water content were related to overactivation of NMDA receptor. Excessive high levels of EAA may be involved in secondary tissue damage following spinal cord injury.展开更多
Objective: To observe the effects of morphine on the excitatory postsynaptic currents (EPSCs) and miniature EPSCs (mEPSCs) in rat supraoptic nucleus (SON) neurons and to explore its synaptic mechanism. Methods: Using ...Objective: To observe the effects of morphine on the excitatory postsynaptic currents (EPSCs) and miniature EPSCs (mEPSCs) in rat supraoptic nucleus (SON) neurons and to explore its synaptic mechanism. Methods: Using whole-cell voltage-clamp recording technique in the brain slices, the EPSCS and mEPSCs of rat SON neurons were recorded, respectively. Results: Morphine (20μmol/L) decreased the frequency of EPSCs and mEPSCs (by 65% for EPSCS and by 45% for mEPSCs), and reduced the amplitude of EPSCs by 44% in all SON neurons, but the amplitude distribution of mEPSCs was not affected. Conclusion: Morphine inhibits the excitatory transmissions via presynaptic mechanisms in SON neurons from rat brain slices.展开更多
To investigate the protective mechanism of nerve growth factor (NGF) on spinal cord injury (SCI), surgical spinal cord injury in Wistar rats was performed by a 10 g2.5 cm impact on the posterior spinal cord at T8 leve...To investigate the protective mechanism of nerve growth factor (NGF) on spinal cord injury (SCI), surgical spinal cord injury in Wistar rats was performed by a 10 g2.5 cm impact on the posterior spinal cord at T8 level, and a thin plastic tube was placed in subarachoid space below the injury level for perfusion of solution. To the experimental animals were given 60 g (20 l liquid) NGF, purified from bovine seminal plasma, at the moment of injury and 1,2,3,4,8,12,24 h after injury. An equal volume of normal saline was given to rats of the control group at the same time. In the expermental group, the injured spinal cord tissue was taken following treatment. The contents of the excitatory amino acids (Glu, Asp) were determined by high performance liquid chromatography (HPLC). Excitatory amino acid contents in the injured spinal cord were significantly increased at 10 min and 8 h after the injury as compared with those in the control group. However, The peak values of the excitatory amino acid contents in NGF group were obviously lowered. NGF might protect spinal cord against injury in vivo. One of the possible mechanisms is that NGF prohibits neurotoxicity of the exitatory amino acids.展开更多
Objective To detect the effect of excitatory ammo add (EAA) in the secondary damage following spinal cord injury (SCI). Methods Glutamate (Glu) and Aspartate (Asp) on the injury site (T8) were studied using a rat SCI ...Objective To detect the effect of excitatory ammo add (EAA) in the secondary damage following spinal cord injury (SCI). Methods Glutamate (Glu) and Aspartate (Asp) on the injury site (T8) were studied using a rat SCI model induced by Allen's weight drop method (10g×2. 5cm). The result suggested that Asp and Glu were significantly increased in 10 mm. Results Glu was significantly decreased from 2 h to 24 h,while Asp was a tittle reduced in 2 h,and slightly rose in 4 h as compared with Control Group. Though elevated in 8 h,it dropped again in 24h as compared with Control Group. Conclusion The result indicates that the rise of EAA following SCI could be the cause of the secondary spinal cord damage.展开更多
BACKGROUND： Many researches have indicated that the imbalances of various amino acid transmitters and neurotransmitters in brain are involved in the formation of alcohol withdrawal, especially that glutamic acid is o...BACKGROUND： Many researches have indicated that the imbalances of various amino acid transmitters and neurotransmitters in brain are involved in the formation of alcohol withdrawal, especially that glutamic acid is one of the important transmitters for alcohol tolerance in central nervous system. OBJECTIVE： To observe the changes of excitatory amino acids in hippocampal dentate gyrus in rats with long-term alcohol drinking after withdrawal under consciousness, and investigate the therapeutic effect of topiramate on alcohol withdrawal. DESIGN ： A randomized control animal experiment SETTING ： Department of Neurology, Affiliated Hospital of Yanbian University MATERIALS： Thirty male Wistar rats of 4 months old, weighing 300-350 g, were purchased from the Experimental Animal Department, Medical College of Yanbian University. Topiramate was produced by Swish Cilag Company, and the batch number was 02CS063. METHODS： The experiments were carried out in the Department of Physiology, Medical College of Yanbian University from August 2005 to February 2006. ① The rats were divided randomly into three groups： control group （n=10）, alcohol group （n=10） and topiramate-treated group （n=10）. Rats in the alcohol group and topiramate-treated group were given intragastric perfusion of 500 g/L alcohol （10 mL/kg）, once a day for 4 weeks successively, and then those in the topiramate-treated group were treated with 80 mg/kg topiramate at 24 hours after the last perfusion of alcohol, once a day for 3 days successively. Rats in the control group were intragastricly given isovolume saline. ② The withdrawal symptoms were assessed at 6, 30, 48 and 72 hours after the last perfusion of alcohol by using the withdrawal rating scale set by Erden et al, which had four observational indexes of stereotyped behaviors, agitation, tail stiffness and abnormal posture, each index was scored by 5 points, the higher the score, the more obvious the symptoms. ③ The contents of aspartic acid and glutamic acid in hippocampal dentate gyrus were detected with microdialysis technique and high-performance liquid chromatograpy （HPLC） respectively at 6, 30, 48 and 72 hours after the last perfusion of alcohol in the three groups. MAIN OUTCOME MEASURES ： ① Scoring results of alcohol withdrawal symptoms; ② Changes of the contents of aspartic acid and glutamic acid in hippocampal dentate gyrus at the alcohol withdrawal symptoms, and the effects of topiramate. RESULTS： Seven rats were excluded due to inaccurate localization and natural death, and 23 rats were involved in the analysis of results. ①In the alcohol group, the scores of alcohol withdrawal symptoms at 30 and 48 hours after the last perfusion of alcohol were obviously higher than those in the control group （10.50±0.96, 14.17±1.25; 3.50±0.92, 3.16±0,31; P 〈 0.01）. In the topiramate-treated group, the scores at 30 hours after the last perfusion of alcohol （6.06±0.82, 3.50±0.92, P 〈 0.05）, and the withdrawal scores at 48 and 72 hours were close to those in the control group （4.57±0.58, 3.30±0.71; 3.16±0.31, 3.66±0.67; P 〉 0.05）.② Changes of the contents of glutamic acid in hippocampal dentate gyrus： In the alcohol group, the content of glutamic acid at 48 hours after the last perfusion of alcohol was significantly increased as compared with that at 6 hours [（143.32±11.42）%, （99.12±0.69）%; P 〈 0.05], and that at 72 hours was close to that at 6 hours [（78.50±16.40）%, （99.12±0.69）%; P 〉 0.05]. The contents of glutamic acid had no obvious differences at 6, 30, 48 and 72 hours after the last perfusion of alcohol in the topiramate-treated group [（100.30±0.37）%, （118.91±10.40）%, （99.55±12.81）%, （99.08±11.42）%; P 〉 0.05], The content of glutamic acid at 48 hours after the last perfusion of alcohol in the topiramate-treated group was obviously lower than that in the alcohol group （P 〈 0.05）, and those at 30 and 72 hours were close （P 〉 0.05）. ③ Changes of the contents of aspartic acid in hippocampal dentate gyrus： In the alcohol group, the contents of aspartic acid at 30 and 48 hours after the last perfusion of alcohol were significantly increased as compared with that at 6 hours [（126.60±8.67）%, （129.17±10.40）%, （99.25±0.87）%; P 〈 0.05], and that at 72 hours was close to that at 6 hours [（89.87±9.93）%, （99.25±0.87）%; P 〉 0.05]. The contents of aspartic acid had no obvious differences at 6, 30, 48 and 72 hours after the last perfusion of alcohol in the topiramate-treated group [（100.27±0.32）%, （120.81 ±12.63）%, （98.91±7.83）%, （85.92±8.07）%; P 〉 0.05]. The content of aspartic acid at 48 hours after the last perfusion of alcohol in the topiramate-treated group was obviously lower than that in the alcohol group （P 〈 0.05）, and those at 30 and 72 hours were close （P 〉 0.05）. CONCLUSION： ① The occurrences of alcohol withdrawal symptoms are correlated with the increased contents of excitatory amino acids in hippocampal dentate gyrus in rats. ② Topiramate can alleviate the alcohol withdrawal symptoms, which may be correlated with the decreased contents of excitatory amino acids in hippocampal dentate gyrus in rats.展开更多
The ability of tetrandrine (Tet), an alkaloid isolated from Radix Stephaniae Tetrandrae, to reduce cortical neuronal injury in cortical cultures derived from fetal rats was quantitatively assessed by examination of mo...The ability of tetrandrine (Tet), an alkaloid isolated from Radix Stephaniae Tetrandrae, to reduce cortical neuronal injury in cortical cultures derived from fetal rats was quantitatively assessed by examination of morphological changes and measurement of lactate dehydrogenase (LDH) released to the extracellular bathing media Cell cultures exposed to the excitatory amino acids (EAA) 50 μmol L 1 glutamate (Glu), 20 μmol L 1 N methyl D aspartate (NMDA), 300 μmol·L 1 β N oxalylamino L alanine (BMAA, NMDA receptor agonist) or 20 μmol·L 1 β N oxaly lamino L alanine (BOAA, non NMDA receptor agonist) for 24 h at 37℃ showed widespread neuronal injury Tet had little effect on the injury induced by 20 μmol·L 1 NMDA but 10 7 and 10 6 μmol·L 1 Tet did partially attenuate the neuronal degeneration, neuronal loss and LDH efflux resulting from prolonged exposures to 100 μmol·L 1 Glu, 300 μmol·L 1 BMAA and 20 μmol·L 1 BOAA respectively The ability of Tet to reduce the neuronal injury induced by prolonged exposure to EAA may contribute, at least in part, to the reduction of Ca 2+ influx through inhibiting the opening of voltagegated Ca 2+ channels Another mechanism that Tet might have a little inhibitory effect on NMDA receptor on neuronal membrane cannot be excluded, as BMAA has been considered to act as a weak NMDA receptor agonist展开更多
Synapse-specific connectivity and dynamics determine microcircuit function but are challenging to explore with classic paired recordings due to their low throughput.We therefore implemented optomapping,a~100-fold fast...Synapse-specific connectivity and dynamics determine microcircuit function but are challenging to explore with classic paired recordings due to their low throughput.We therefore implemented optomapping,a~100-fold faster two-photon optogenetic method.In mouse primary visual cortex(V1),we optomapped 30,454 candidate inputs to reveal 1,790 excitatory inputs to pyramidal,basket,and Martinotti cells.Across these cell types,log-normal distribution of synaptic efficacies emerged as a principle.For pyramidal cells,optomapping reproduced the canonical circuit but unexpectedly uncovered that the excitation of basket cells concentrated to layer 5 and that of Martinotti cells dominated in layer 2/3.The excitation of basket cells was stronger and reached farther than the excitation of pyramidal cells,which may promote stability.Short-term plasticity surprisingly depended on cortical layer in addition to target cell.Finally,optomapping revealed an overrepresentation of shared inputs for interconnected layer-6 pyramidal cells.Thus,by resolving the throughput problem,optomapping uncovered hitherto unappreciated principles of V1 structure.展开更多
基金supported by the National Natural Science Foundation of China,Nos.32371070 (to JT),31761163005 (to JT),32100824 (to QX)the Shenzhen Science and Technology Program,Nos.RCBS20210609104606024 (to QX),JCY20210324101813035 (to DL)+4 种基金the Guangdong Provincial Key S&T Program,No.2018B030336001 (to JT)the Key Basic Research Program of Shenzhen Science and Technology Innovation Commission,Nos.JCYJ20200109115405930 (to JT),JCYJ20220818101615033 (to DL),JCYJ20210324115811031 (to QX),JCYJ20200109150717745 (to QX)Shenzhen Key Laboratory of Neuroimmunomodulation for Neurological Diseases,No.ZDSYS20220304163558001 (to JT)Guangdong Provincial Key Laboratory of Brain Connectome and Behavior,No.2023B1212060055 (to JT)the China Postdoctoral Science Foundation,No.2021M693298 (to QX)。
文摘The conventional perception of astrocytes as mere supportive cells within the brain has recently been called into question by empirical evidence, which has revealed their active involvement in regulating brain function and encoding behaviors associated with emotions.Specifically, astrocytes in the basolateral amygdala have been found to play a role in the modulation of anxiety-like behaviors triggered by chronic stress. Nevertheless, the precise molecular mechanisms by which basolateral amygdala astrocytes regulate chronic stress–induced anxiety-like behaviors remain to be fully elucidated. In this study, we found that in a mouse model of anxiety triggered by unpredictable chronic mild stress, the expression of excitatory amino acid transporter 2 was upregulated in the basolateral amygdala. Interestingly, our findings indicate that the targeted knockdown of excitatory amino acid transporter 2 specifically within the basolateral amygdala astrocytes was able to rescue the anxiety-like behavior in mice subjected to stress. Furthermore, we found that the overexpression of excitatory amino acid transporter 2 in the basolateral amygdala, whether achieved through intracranial administration of excitatory amino acid transporter 2agonists or through injection of excitatory amino acid transporter 2-overexpressing viruses with GfaABC1D promoters, evoked anxiety-like behavior in mice. Our single-nucleus RNA sequencing analysis further confirmed that chronic stress induced an upregulation of excitatory amino acid transporter 2 specifically in astrocytes in the basolateral amygdala. Moreover, through in vivo calcium signal recordings, we found that the frequency of calcium activity in the basolateral amygdala of mice subjected to chronic stress was higher compared with normal mice.After knocking down the expression of excitatory amino acid transporter 2 in the basolateral amygdala, the frequency of calcium activity was not significantly increased, and anxiety-like behavior was obviously mitigated. Additionally, administration of an excitatory amino acid transporter 2 inhibitor in the basolateral amygdala yielded a notable reduction in anxiety level among mice subjected to stress. These results suggest that basolateral amygdala astrocytic excitatory amino acid transporter 2 plays a role in in the regulation of unpredictable chronic mild stress-induced anxiety-like behavior by impacting the activity of local glutamatergic neurons, and targeting excitatory amino acid transporter 2 in the basolateral amygdala holds therapeutic promise for addressing anxiety disorders.
基金supported by the National Natural Science Foundation of China,No. 81771228Shanghai Association of Science and Technology,Nos. 22WZ2501700 and 23WZ2504500 (all to LY)
文摘Bromodomain and plant homeodomain(PHD)finger containing protein 1(Brpf1)is an activator and scaffold protein of a multiunit complex that includes other components involving lysine acetyltransferase(KAT)6A/6B/7.Brpf1,KAT6A,and KAT6B mutations were identified as the causal genes of neurodevelopmental disorders leading to intellectual disability.Our previous work revealed strong and specific expression of Brpf1 in both the postnatal and adult forebrain,especially the hippocampus,which has essential roles in learning and memory.Here,we hypothesized that Brpf1 plays critical roles in the function of forebrain excitatory neurons,and that its deficiency leads to learning and memory deficits.To test this,we knocked out Brpf1 in forebrain excitatory neurons using CaMKIIa-Cre.We found that Brpf1 deficiency reduced the frequency of miniature excitatory postsynaptic currents and downregulated the expression of genes Pcdhgb1,Slc16a7,Robo3,and Rho,which are related to neural development,synapse function,and memory,thereby damaging spatial and fear memory in mice.These findings help explain the mechanisms of intellectual impairment in patients with BRPF1 mutation.
基金This study was supported by the grant from ClimbingProgram of Chinese Committee of Science
文摘BZ]Dendro dendritic and dendro somatic projections are common between spinal motoneurons. We attempted to clarify whether there are functional connections through these projections. Methods. Motoneurons were antidromically stimulated by the muscle nerve and recorded intracellularly to examine the direct interaction between them, after the related dorsal roots had been cut. Results. Excitatory connections, demonstrated by depolarizing potentials in response to muscle nerve stimulation, were found between motoneurons innervating the same muscle or synergistic muscles, but never between motoneurons innervating antagonistic muscles. These potentials were finely graded in response to a series of increasing stimuli and resistant to high frequency (50Hz) stimulation. Conclusions.These results indicate that excitatory connections, with certain specificity of spatial and temporal distribution, occur in the spinal motoneurons. It is also suggested that electrical coupling should be involved in these connections and this mechanism should improve the excitability of the motoneurons in the same column.
基金supported by grants from the National Natural Science Foundation of China (81790642, 31671078, and 81430007)
文摘Ras-related C3 botulinum toxin substrate 1(Racl),a member of the Rho GTPase family which plays important roles in dendritic spine morphology and plasticity,is a key regulator of cytoskeletal reorganization in dendrites and spines.Here,we investigated whether and how Racl modulates synaptic transmission in mouse retinal ganglion cells(RGCs)using selective conditional knockout of Racl(Racl-cKO).Racl-cKO significantly reduced the frequency of AMPA receptor-mediated miniature excitatory postsynaptic currents,while glycine/GABA_A receptor-mediated miniature inhibitory postsynaptic currents were not affected.Although the total GluA1 protein level was increased in Racl-cKO mice,its expression in the membrane component was unchanged.RaclcKO did not affect spine-like branch density in single dendrites,but significantly reduced the dendritic complexity,which resulted in a decrease in the total number of dendritic spine-like branches.These results suggest that Racl selectively affects excitatory synaptic transmission in RGCs by modulating dendritic complexity.
基金supported by the National Natural Science Foundation of China(61890953.61890954,and 31871088)the CAMS Innovation Fund for Medical Sciences(2019-12M5014).
文摘Neurons in the primary auditory area(AUDp)innervate multiple brain regions with long-range projections while receiving informative inputs for diverse functions.However,the brain-wide connections of these neurons have not been comprehensively investigated.Here,we simultaneously applied virus-based anterograde and retrograde tracing,labeled the connections of excitatory and inhibitory neurons in the mouse AUDp,and acquired whole-brain information using a dual-channel fuorescence micro-optical sectioning tomography system.Quantified results showed that the two types of neurons received inputs with similar patterns but sent heterogeneous projections to downstream regions.In the isocortex,functionally different areas consistently sent feedback-dominated projections to these neurons,with concomitant laterallydominated projections from the sensory and limbic cortices to inhibitory neurons.In subcortical regions,the dorsal and medial parts of the non-lemniscal auditory thalamus(AT)were reciprocally connected to the AUDp,while the ventral part contained the most fibers of passage from the excitatory neurons and barely sent projections back,indicating the regional heterogeneity of the AUDp-AT circuit.Our results reveal details of the whole-brain network and provide new insights for further physiological and functional studies of the AUDp.
基金supported by the National Natural Science Foundation of China, No. 30960398the 47th Post-doctoral Scientific Foundation of China, No. 20100470376the Natural Science Foundation of Yunnan Province, No.2009CD178
文摘Selective cerebral deep hypothermia and blood flow occlusion can enhance brain tolerance to ischemia and hypoxia and reduce cardiopulmonary complications in monkeys. Excitotoxicity induced by the release of a large amount of excitatory amino acids after cerebral ischemia is the major mechanism underlying ischemic brain injury and nerve cell death. In the present study, we used selective cerebral deep hypothermia and blood flow occlusion to block the bilateral common carotid arteries and/or bilateral vertebral arteries in rhesus monkey, followed by reperfusion using Ringer＇s solution at 4~C. Microdialysis and transmission electron microscope results showed that selective cerebral deep hypothermia and blood flow occlusion inhibited the release of glutamic acid into the extracellular fluid in the brain frontal lobe and relieved pathological injury in terms of the ultrastructure of brain tissues after severe cerebral ischemia. These findings indicate that cerebral deep hypothermia and blood flow occlusion can inhibit cytotoxic effects and attenuate ischemic/ hypoxic brain injury through decreasing the release of excitatory amino acids, such as glutamic acid.
文摘Aim Prenatal stress （PS） can lead to abnormal behavior of offspring and increase the incidence of mental illness. Previous researches have shown that levels of glutamate and its receptor expression are closely relat- ed to the occurrence of this phenomenon. Furthermore, recent study has demonstrated that the expression levels of excitatory amino acid transporters 2 （EAAT2） in different brain regions of 1 month PS offspring rats have changed. Methods The SD pregnant rats were used restraint stress to imitate PS from gestation 14 -~ 19 days. Offspring rats were weaned 21 days after birth. The expression of EAAT2 of hippocampus was observed by Western blot. Results The expression of EAAT2 of 1 month PS offspring rats was significantly decreased in comparison to control group. However, the expression of EAAT2 of 2 month PS offspring rats was significantly increased in comparison to 1 month PS offspring rats. Conclusion These phenomena have illustrated that the expression of EAAT2 of PS off- spring rats could show time dependence or reversibility. The expression of EAAT2 may play an important role in the development of mental illness of offspring rats influenced by PS.
基金the National Natural Science Foundation of China(Grant Nos.11872276 and 11762001)the Young Talents of Science and Technology in Universities of Inner Mongolia Autonomous Region,China(Grant No.NJYT-20-A09).
文摘In traditional viewpoint,excitatory modulation always promotes neural firing activities.On contrary,the negative responses of complex bursting behaviors to excitatory self-feedback mediated by autapse with time delay are acquired in the present paper.Two representative bursting patterns which are identified respectively to be“Fold/Big Homoclinic”bursting and“Circle/Fold cycle”bursting with bifurcations are studied.For both burstings,excitatory modulation can induce less spikes per burst for suitable time delay and strength of the self-feedback/autapse,because the modulation can change the initial or termination phases of the burst.For the former bursting composed of quiescent state and burst,the mean firing frequency exhibits increase,due to that the quiescent state becomes much shorter than the burst.However,for the latter bursting pattern with more complex behavior which is depolarization block lying between burst and quiescent state,the firing frequency manifests decrease in a wide range of time delay and strength,because the duration of both depolarization block and quiescent state becomes long.Therefore,the decrease degree of spike number per burst is larger than that of the bursting period,which is the cause for the decrease of firing frequency.Such reduced bursting activity is explained with the relations between the bifurcation points of the fast subsystem and the bursting trajectory.The present paper provides novel examples of paradoxical phenomenon that the excitatory effect induces negative responses,which presents possible novel modulation measures and potential functions of excitatory self-feedback/autapse to reduce bursting activities.
基金Supported by the National Natural Science Foundation of China under Grant Nos. 10975015 and 11174034the Fundamental Research Funds for the Central Universities
文摘Zn neural networks, both excitatory and inhibitory cells play important roles in determining the functions of systems. Various dynamical networks have been proposed as artificial neural networks to study the properties of biological systems where the influences of excitatory nodes have been extensively investigated while those of inhibitory nodes have been studied much less. In this paper, we consider a model of oscillatory networks of excitable Boolean maps consisting of both excitatory and inhibitory nodes, focusing on the roles of inhibitory nodes. We find that inhibitory nodes in sparse networks （smM1 average connection degree） play decisive roles in weakening oscillations, and oscillation death occurs after continual weakening of oscillation for sufficiently high inhibitory node density. In the sharp contrast, increasing inhibitory nodes in dense networks may result in the increase of oscillation amplitude and sudden oscillation death at much lower inhibitory node density and the nearly highest excitation activities. Mechanism under these peculiar behaviors of dense networks is explained by the competition of the duplex effects of inhibitory nodes.
基金a grant from Health Department of Hunan Province,No.B2006-204
文摘BACKGROUND： Under normal conditions, excitatory amino acids are dynamically balanced with inhibitory amino acids. Excitatory amino acids have been implicated in perinatal brain injury. OBJECTIVE： To investigate differences in the levels of the excitatory amino acids glutamic acid and aspartic acid, and the inhibitory amino acid gamma-aminobutyric acid （GABA） in the cerebrospinal fluid （CSF） of children with spastic cerebral palsy or athetotic cerebral palsy. DESIGN, TIME AND SETTING： Case-control exploratory observation of neurotransmitter in patients. The experiment was performed in the Pediatrics Department of the Second Affiliated Hospital of Changsha Medical College, the Cerebral Palsy Center of Xiangtan Affiliated Hospital of South China University and the Pediatrics Department of Xiangya Hospital, between February 2006 and May 2007. PARTICIPANTS： We selected 27 children with cerebral palsy, including 13 with spastic cerebral palsy and 14 with athetotic cerebral palsy. We selected 10 patients who were not affected by any neurological disease as controls. METHODS： Two mL blood-free CSF was harvested between the third and fourth lumbar vertebrae of each patient after anesthesia, and stored at -70℃. One mL CSF was mixed with 10 mg sulfosalicylic acid and placed in ice-bath for 10 minutes, then centrifuged 2 000 g for 10 minutes. The supernatant was collected for amino acid quantitation. MAIN OUTCOME MEASURES： The concentrations of glutamic acid, aspartic acid and GABA in the CSF were determined by high-performance liquid chromatography and fluorometric method. The correlation of glutamic acid, aspartic acid and GABA levels with muscular tension in children with cerebral palsy was analyzed using linear dependence. RESULTS： The concentration of GABA was significantly lower in both spastic cerebral palsy and athetotic cerebral palsy patients than in the control group （P 〈 0.01）. Glutamic acid and aspartic acid were significantly higher in both cerebral palsy groups than in the control group （P 〈 0.05-0.01）. The concentration of GABA was significantly decreased in spastic cerebral palsy patients compared with the athetotic cerebral palsy group （P 〈 0.05）. Muscular tension was positively correlated with the concentration of glutamic acid in spastic cerebral palsy patients （P 〈 0.05） but there was no significant correlation between aspartic acid or GABA and muscular tension （P 〉 0.05）. CONCLUSION： Spastic cerebral palsy and athetotic cerebral palsy patients exhibit an imbalance of excitatory amino acids and inhibitory amino acids in their CSF： an increase in glutamic acid and aspartic acid, and a decrease in GABA. Amino acid levels are different in the CSF in varied types of cerebral palsy.
基金Project supported by the National Natural Science Foundation of China(Grant Nos.12072236,12162002,and11802086)the Young Talents of Science and Technology in Universities of Inner Mongolia Autonomous Region(Grant No.NJYT-20-A09)the Program for Excellent Young Talents in Colleges and Universities of Anhui Province of China(Grant No.gxyq ZD2020077)。
文摘Different from the common delayed synchronization(DS)in which response appears after stimulation,anticipated synchronization(AS)in unidirectionally coupled neurons denotes a counterintuitive phenomenon in which response of the receiver neuron appears before stimulation of the sender neuron,showing an interesting function of brain to anticipate the future.The dynamical mechanism for the AS remains unclear due to complex dynamics of inhibitory and excitatory modulations.In this article,the paradoxical roles of excitatory synapse and inhibitory autapse in the formation of AS are acquired.Firstly,in addition to the common roles such that inhibitory modulation delays and excitatory modulation advances spike,paradoxical roles of excitatory stimulation to delay spike via type-II phase response and of inhibitory autapse to advance spike are obtained in suitable parameter regions,extending the dynamics and functions of the excitatory and inhibitory modulations.Secondly,AS is related to the paradoxical roles of the excitatory and inhibitory modulations,presenting deep understandings to the AS.Inhibitory autapse induces spike of the receiver neuron advanced to appear before that of the sender neuron at first,and then excitatory synapse plays a delay role to prevent the spike further advanced,resulting in the AS as the advance and delay effects realize a dynamic balance.Lastly,inhibitory autapse with strong advance,middle advance,and weak advance and delay effects induce phase drift(spike of the receiver neuron advances continuously),AS,and DS,respectively,presenting comprehensive relationships between AS and other behaviors.The results present potential measures to modulate AS related to brain function.
文摘Excitation and inhibition are at the core of brain function and malfunction.To sustain the activity of neuronal networks over time and space,glutamatergic excitation is balanced by GABAergic inhibition.The equipoise of excitation and inhibition,known as the excitation/inhibition(E/I)balance,is crucial for proper brain function.The E/I balance is highly dynamic and shifts across different brain states:wakefulness primarily augments excitatory activity,while sleep promotes a decrease in excitation and an increase in inhibition(Bridi et al.,2020).Neuronal activity during various brain states is primarily regulated by neurotransmitters(Schiemann et al.,2015),alongside non-synaptic mechanisms that operate on a slower timescale.The non-synaptic mechanisms are many,with the ionic composition of the extracellular space playing a significant role;altering extracellular ion concentrations affects sleep,arousal,electroencephalogram patterns,and behavioral states(Ding et al.,2016).
文摘To elucidate the correlation between excitatory amino acids (EAA) and spinal cord injury, we investigat-ed the dynamic changes in excitatory amino acids, aspartate (Asp) and glutamate (Gin ) contents in cerebrospinalfluid (CSF) of 26 patients with acute spinal cord injury by amino acids autoanalyzer. The results showed that con-tent of glutanlate and aspartate was renlarkably elevated in 24 h after trauma and was related to the seventy of injury. The more severe the spinal cord injured, the more remarkable the content of Asp and Gin in CSF increased.The more pronounced the content of EAA in CSF increased, the worse the patient’s prognosis was. Content of EAA in CSF after spinal cord injury may be an indicator to judge injury extent and prognosis. and provide further support for a potential pathophysiological role of EAA in spinal cord injury.
文摘Sprague-Dawley rats were subjected to traumatic spinal cord injury using Allen's method. Regional concentrations of excitatory amino acid (EAA) were assessed by high-performance liquid chromatography, and regional water and ion content were measured by the atomic absorption spectrophotometry at various times after intrathecal administration of different dosage of 3-(2-carboxypiperazin-4-yl)-propyl-1-phosphonic acid (CPP),a specific antagonist of N-methyl-D-aspartame (NMDA) receptor,to rat at 48 h posttrauma.The results showed that concentrations of glutamate and aspartate were elevated rapidly at 15, 30 min and were correlated positively with the severity of injury. In the injured segment there was a significant increase in water, Na+ ,Ca++ content and a decrease in K+ , Mg++. Whereas in CPP treated groups they had a statistically significant return, which was related to the dosage and time of administration. This effect of CPP suggests that ion and water content were related to overactivation of NMDA receptor. Excessive high levels of EAA may be involved in secondary tissue damage following spinal cord injury.
文摘Objective: To observe the effects of morphine on the excitatory postsynaptic currents (EPSCs) and miniature EPSCs (mEPSCs) in rat supraoptic nucleus (SON) neurons and to explore its synaptic mechanism. Methods: Using whole-cell voltage-clamp recording technique in the brain slices, the EPSCS and mEPSCs of rat SON neurons were recorded, respectively. Results: Morphine (20μmol/L) decreased the frequency of EPSCs and mEPSCs (by 65% for EPSCS and by 45% for mEPSCs), and reduced the amplitude of EPSCs by 44% in all SON neurons, but the amplitude distribution of mEPSCs was not affected. Conclusion: Morphine inhibits the excitatory transmissions via presynaptic mechanisms in SON neurons from rat brain slices.
文摘To investigate the protective mechanism of nerve growth factor (NGF) on spinal cord injury (SCI), surgical spinal cord injury in Wistar rats was performed by a 10 g2.5 cm impact on the posterior spinal cord at T8 level, and a thin plastic tube was placed in subarachoid space below the injury level for perfusion of solution. To the experimental animals were given 60 g (20 l liquid) NGF, purified from bovine seminal plasma, at the moment of injury and 1,2,3,4,8,12,24 h after injury. An equal volume of normal saline was given to rats of the control group at the same time. In the expermental group, the injured spinal cord tissue was taken following treatment. The contents of the excitatory amino acids (Glu, Asp) were determined by high performance liquid chromatography (HPLC). Excitatory amino acid contents in the injured spinal cord were significantly increased at 10 min and 8 h after the injury as compared with those in the control group. However, The peak values of the excitatory amino acid contents in NGF group were obviously lowered. NGF might protect spinal cord against injury in vivo. One of the possible mechanisms is that NGF prohibits neurotoxicity of the exitatory amino acids.
文摘Objective To detect the effect of excitatory ammo add (EAA) in the secondary damage following spinal cord injury (SCI). Methods Glutamate (Glu) and Aspartate (Asp) on the injury site (T8) were studied using a rat SCI model induced by Allen's weight drop method (10g×2. 5cm). The result suggested that Asp and Glu were significantly increased in 10 mm. Results Glu was significantly decreased from 2 h to 24 h,while Asp was a tittle reduced in 2 h,and slightly rose in 4 h as compared with Control Group. Though elevated in 8 h,it dropped again in 24h as compared with Control Group. Conclusion The result indicates that the rise of EAA following SCI could be the cause of the secondary spinal cord damage.
文摘BACKGROUND： Many researches have indicated that the imbalances of various amino acid transmitters and neurotransmitters in brain are involved in the formation of alcohol withdrawal, especially that glutamic acid is one of the important transmitters for alcohol tolerance in central nervous system. OBJECTIVE： To observe the changes of excitatory amino acids in hippocampal dentate gyrus in rats with long-term alcohol drinking after withdrawal under consciousness, and investigate the therapeutic effect of topiramate on alcohol withdrawal. DESIGN ： A randomized control animal experiment SETTING ： Department of Neurology, Affiliated Hospital of Yanbian University MATERIALS： Thirty male Wistar rats of 4 months old, weighing 300-350 g, were purchased from the Experimental Animal Department, Medical College of Yanbian University. Topiramate was produced by Swish Cilag Company, and the batch number was 02CS063. METHODS： The experiments were carried out in the Department of Physiology, Medical College of Yanbian University from August 2005 to February 2006. ① The rats were divided randomly into three groups： control group （n=10）, alcohol group （n=10） and topiramate-treated group （n=10）. Rats in the alcohol group and topiramate-treated group were given intragastric perfusion of 500 g/L alcohol （10 mL/kg）, once a day for 4 weeks successively, and then those in the topiramate-treated group were treated with 80 mg/kg topiramate at 24 hours after the last perfusion of alcohol, once a day for 3 days successively. Rats in the control group were intragastricly given isovolume saline. ② The withdrawal symptoms were assessed at 6, 30, 48 and 72 hours after the last perfusion of alcohol by using the withdrawal rating scale set by Erden et al, which had four observational indexes of stereotyped behaviors, agitation, tail stiffness and abnormal posture, each index was scored by 5 points, the higher the score, the more obvious the symptoms. ③ The contents of aspartic acid and glutamic acid in hippocampal dentate gyrus were detected with microdialysis technique and high-performance liquid chromatograpy （HPLC） respectively at 6, 30, 48 and 72 hours after the last perfusion of alcohol in the three groups. MAIN OUTCOME MEASURES ： ① Scoring results of alcohol withdrawal symptoms; ② Changes of the contents of aspartic acid and glutamic acid in hippocampal dentate gyrus at the alcohol withdrawal symptoms, and the effects of topiramate. RESULTS： Seven rats were excluded due to inaccurate localization and natural death, and 23 rats were involved in the analysis of results. ①In the alcohol group, the scores of alcohol withdrawal symptoms at 30 and 48 hours after the last perfusion of alcohol were obviously higher than those in the control group （10.50±0.96, 14.17±1.25; 3.50±0.92, 3.16±0,31; P 〈 0.01）. In the topiramate-treated group, the scores at 30 hours after the last perfusion of alcohol （6.06±0.82, 3.50±0.92, P 〈 0.05）, and the withdrawal scores at 48 and 72 hours were close to those in the control group （4.57±0.58, 3.30±0.71; 3.16±0.31, 3.66±0.67; P 〉 0.05）.② Changes of the contents of glutamic acid in hippocampal dentate gyrus： In the alcohol group, the content of glutamic acid at 48 hours after the last perfusion of alcohol was significantly increased as compared with that at 6 hours [（143.32±11.42）%, （99.12±0.69）%; P 〈 0.05], and that at 72 hours was close to that at 6 hours [（78.50±16.40）%, （99.12±0.69）%; P 〉 0.05]. The contents of glutamic acid had no obvious differences at 6, 30, 48 and 72 hours after the last perfusion of alcohol in the topiramate-treated group [（100.30±0.37）%, （118.91±10.40）%, （99.55±12.81）%, （99.08±11.42）%; P 〉 0.05], The content of glutamic acid at 48 hours after the last perfusion of alcohol in the topiramate-treated group was obviously lower than that in the alcohol group （P 〈 0.05）, and those at 30 and 72 hours were close （P 〉 0.05）. ③ Changes of the contents of aspartic acid in hippocampal dentate gyrus： In the alcohol group, the contents of aspartic acid at 30 and 48 hours after the last perfusion of alcohol were significantly increased as compared with that at 6 hours [（126.60±8.67）%, （129.17±10.40）%, （99.25±0.87）%; P 〈 0.05], and that at 72 hours was close to that at 6 hours [（89.87±9.93）%, （99.25±0.87）%; P 〉 0.05]. The contents of aspartic acid had no obvious differences at 6, 30, 48 and 72 hours after the last perfusion of alcohol in the topiramate-treated group [（100.27±0.32）%, （120.81 ±12.63）%, （98.91±7.83）%, （85.92±8.07）%; P 〉 0.05]. The content of aspartic acid at 48 hours after the last perfusion of alcohol in the topiramate-treated group was obviously lower than that in the alcohol group （P 〈 0.05）, and those at 30 and 72 hours were close （P 〉 0.05）. CONCLUSION： ① The occurrences of alcohol withdrawal symptoms are correlated with the increased contents of excitatory amino acids in hippocampal dentate gyrus in rats. ② Topiramate can alleviate the alcohol withdrawal symptoms, which may be correlated with the decreased contents of excitatory amino acids in hippocampal dentate gyrus in rats.
文摘The ability of tetrandrine (Tet), an alkaloid isolated from Radix Stephaniae Tetrandrae, to reduce cortical neuronal injury in cortical cultures derived from fetal rats was quantitatively assessed by examination of morphological changes and measurement of lactate dehydrogenase (LDH) released to the extracellular bathing media Cell cultures exposed to the excitatory amino acids (EAA) 50 μmol L 1 glutamate (Glu), 20 μmol L 1 N methyl D aspartate (NMDA), 300 μmol·L 1 β N oxalylamino L alanine (BMAA, NMDA receptor agonist) or 20 μmol·L 1 β N oxaly lamino L alanine (BOAA, non NMDA receptor agonist) for 24 h at 37℃ showed widespread neuronal injury Tet had little effect on the injury induced by 20 μmol·L 1 NMDA but 10 7 and 10 6 μmol·L 1 Tet did partially attenuate the neuronal degeneration, neuronal loss and LDH efflux resulting from prolonged exposures to 100 μmol·L 1 Glu, 300 μmol·L 1 BMAA and 20 μmol·L 1 BOAA respectively The ability of Tet to reduce the neuronal injury induced by prolonged exposure to EAA may contribute, at least in part, to the reduction of Ca 2+ influx through inhibiting the opening of voltagegated Ca 2+ channels Another mechanism that Tet might have a little inhibitory effect on NMDA receptor on neuronal membrane cannot be excluded, as BMAA has been considered to act as a weak NMDA receptor agonist
基金supported by CIHR 295104,HBHL,FRQS 259572,and RBIQ 35450 fellowships.C.G.won NSERC USRA,FRQNT BPC,RI-MUHC,FRQS,and CIHR CGS-M studentships.K.E.B.was funded by IBRO.T.A.L.won the NSERC USRA.P.J.S.is funded by the MGH FoundationCFI LOF 28331+2 种基金CIHR PGs 156223,191969,and 191997FRSQ CB 254033NSERC DG/DAS 2024-06712,2017-04730,and 2017-507818。
文摘Synapse-specific connectivity and dynamics determine microcircuit function but are challenging to explore with classic paired recordings due to their low throughput.We therefore implemented optomapping,a~100-fold faster two-photon optogenetic method.In mouse primary visual cortex(V1),we optomapped 30,454 candidate inputs to reveal 1,790 excitatory inputs to pyramidal,basket,and Martinotti cells.Across these cell types,log-normal distribution of synaptic efficacies emerged as a principle.For pyramidal cells,optomapping reproduced the canonical circuit but unexpectedly uncovered that the excitation of basket cells concentrated to layer 5 and that of Martinotti cells dominated in layer 2/3.The excitation of basket cells was stronger and reached farther than the excitation of pyramidal cells,which may promote stability.Short-term plasticity surprisingly depended on cortical layer in addition to target cell.Finally,optomapping revealed an overrepresentation of shared inputs for interconnected layer-6 pyramidal cells.Thus,by resolving the throughput problem,optomapping uncovered hitherto unappreciated principles of V1 structure.
