Working memory deficits in Parkinson's disease mouse model / 中国药理学与毒理学杂志

OBJECTIVE Parkinson's disease(PD)is a progressive neurodegenerative disease clinically char-acterized by dyskinesia,tremor,rigidity,abnormal gait,whereas 90%of patients with PD suffer from defects of the sense of smell before the appearance of the motor dysfunctions.However,the mechanism of olfactory disor-der is still not clear.METHODS We utilized olfaction based delayed paired association task in head-fixed mice.We focused on functional role of neural circuit using opto-genetic techniques.In addition,we viewed the synaptic transmission by slice physiological recording and count-ed the cell number of targeted circuits.RESULTS AND CONCLUSION In our experiments,olfactory working memory impairments were found in the PD mice,and the working memory impairment appeared before motor dys-functions.Furthermore,we also investigated the functional role of neural circuit for olfactory working memory in PD mice.Meanwhile,the excitatory post synaptic currents were decreased as a result of presynaptic release proba-bility suppression in PD mice.However cell loss wasn't found in working memory related circuit recently.These will provide a new idea of clinic diagnosis for PD.

Loss of O-GlcNAcylation on MeCP2 at Threonine 203 Leads to Neurodevelopmental Disorders / 神经科学通报·英文版

Mutations of the X-linked methyl-CpG-binding protein 2 (MECP2) gene in humans are responsible for most cases of Rett syndrome (RTT), an X-linked progressive neurological disorder. While genome-wide screens in clinical trials have revealed several putative RTT-associated mutations in MECP2, their causal relevance regarding the functional regulation of MeCP2 at the etiologic sites at the protein level requires more evidence. In this study, we demonstrated that MeCP2 was dynamically modified by O-linked-β-N-acetylglucosamine (O-GlcNAc) at threonine 203 (T203), an etiologic site in RTT patients. Disruption of the O-GlcNAcylation of MeCP2 specifically at T203 impaired dendrite development and spine maturation in cultured hippocampal neurons, and disrupted neuronal migration, dendritic spine morphogenesis, and caused dysfunction of synaptic transmission in the developing and juvenile mouse cerebral cortex. Mechanistically, genetic disruption of O-GlcNAcylation at T203 on MeCP2 decreased the neuronal activity-induced induction of Bdnf transcription. Our study highlights the critical role of MeCP2 T203 O-GlcNAcylation in neural development and synaptic transmission potentially via brain-derived neurotrophic factor.

CCL2/CCR2 Contributes to the Altered Excitatory-inhibitory Synaptic Balance in the Nucleus Accumbens Shell Following Peripheral Nerve Injury-induced Neuropathic Pain / 神经科学通报·英文版

The medium spiny neurons (MSNs) in the nucleus accumbens (NAc) integrate excitatory and inhibitory synaptic inputs and gate motivational and emotional behavior output. Here we report that the relative intensity of excitatory and inhibitory synaptic inputs to MSNs of the NAc shell was decreased in mice with neuropathic pain induced by spinal nerve ligation (SNL). SNL increased the frequency, but not the amplitude of spontaneous inhibitory postsynaptic currents (sIPSCs), and decreased both the frequency and amplitude of spontaneous excitatory postsynaptic currents (sEPSCs) in the MSNs. SNL also decreased the paired-pulse ratio (PPR) of evoked IPSCs but increased the PPR of evoked EPSCs. Moreover, acute bath application of C–C motif chemokine ligand 2 (CCL2) increased the frequency and amplitude of sIPSCs and sEPSCs in the MSNs, and especially strengthened the amplitude of N-methyl-D-aspartate receptor (NMDAR)-mediated miniature EPSCs. Further Ccl2 overexpression in the NAc in vivo decreased the peak amplitude of the sEPSC/sIPSC ratio. Finally, Ccr2 knock-down improved the impaired induction of NMDAR-dependent long-term depression (LTD) in the NAc after SNL. These results suggest that CCL2/CCR2 signaling plays a role in the integration of excitatory/inhibitory synaptic transmission and leads to an increase of the LTD induction threshold at the synapses of MSNs during neuropathic pain.

Orexin B Enhances the Synaptic Transmission from LGN to Orexin-sensitive Neurons in L6b of Visual Cortex / 中山大学学报(医学科学版)

@#【Objective】To unmask the effect of Orexin B on the synaptic transmission between feed-forward projection from the lateral geniculate nucleus（LGN）to orexin-sensitive neurons in layer 6b（L6b）of visual cortex（VC）.【Methods】C57 mice at P25-P30 were used for micro-injection of CTB555 and ChR2-EGFP into LGN to label the neurons feedback projection to LGN from L6b and the feed-forward projection from LGN to the neurons in L6b of VC respectively. The EPSC in L6b cells was intracellularly recorded from the neurons labeled by CTB555.【Results】The neurons feedback projection to LGN in L6b are mainly pyramidal neurons, and the most of these cells are activated by orexin B，called orexin- sensitive neurons. Orexin B enhanced the NMDAR-mediated postsynaptic current in orexin-sensitive neurons in L6b by electrical or optical stimulation on the LGN projection to VC［electrical stimulation：（125.1 ± 3.7）%，optical stimulation：（123.8 ±3.8）%. In the case of OX2R′s blocker，the effect of Orexin B on EPSC amplitude disappeared with significant statistical significance，P < 0.05］，thus，strengthening the synaptic transmission between LGN and orexin-sensitive neurons in L6b.【Conclusions】Orexin B enhances the synaptic transmission between LGN to pyramidal neurons in L6b of VC.

Layer-specific cholinergic modulation of synaptic transmission in layer 2/3 pyramidal neurons of rat visual cortex

It is known that top-down associative inputs terminate on distal apical dendrites in layer 1 while bottom-up sensory inputs terminate on perisomatic dendrites of layer 2/3 pyramidal neurons (L2/3 PyNs) in primary sensory cortex. Since studies on synaptic transmission in layer 1 are sparse, we investigated the basic properties and cholinergic modulation of synaptic transmission in layer 1 and compared them to those in perisomatic dendrites of L2/3 PyNs of rat primary visual cortex. Using extracellular stimulations of layer 1 and layer 4, we evoked excitatory postsynaptic current/potential in synapses in distal apical dendrites (L1-EPSC/L1-EPSP) and those in perisomatic dendrites (L4-EPSC/L4-EPSP), respectively. Kinetics of L1-EPSC was slower than that of L4-EPSC. L1-EPSC showed presynaptic depression while L4-EPSC was facilitating. In contrast, inhibitory postsynaptic currents showed similar paired-pulse ratio between layer 1 and layer 4 stimulations with depression only at 100 Hz. Cholinergic stimulation induced presynaptic depression by activating muscarinic receptors in excitatory and inhibitory synapses to similar extents in both inputs. However, nicotinic stimulation enhanced excitatory synaptic transmission by ~20% in L4-EPSC. Rectification index of AMPA receptors and AMPA/NMDA ratio were similar between synapses in distal apical and perisomatic dendrites. These results provide basic properties and cholinergic modulation of synaptic transmission between distal apical and perisomatic dendrites in L2/3 PyNs of the visual cortex, which might be important for controlling information processing balance depending on attentional state.

Research progress of P2X7 receptors involved in pain regulation / 中国药理学通报

The ATP-gated ionotropic P2X7 receptor has been widely concerned in recent years. Upon activation by ATP and its derivatives, P2X7 receptor induces a series of responses such as activation of PANX1 and release of IL-lg. Elucidation of the role and mechanism of P2X7 receptor in pain would provide ideas for the development of new and effective analgesic drugs. This review discusses the recent progress of P2X7 receptor in inflammatory pain, neuropathic pain, cancer pain, and morphine tol-erance , and summarizes the possible mechanism of P2X7 receptor involved in the modulation of pain.

Rac1 Modulates Excitatory Synaptic Transmission in Mouse Retinal Ganglion Cells / 神经科学通报·英文版

Ras-related C3 botulinum toxin substrate 1 (Rac1), 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 Rac1 modulates synaptic transmission in mouse retinal ganglion cells (RGCs) using selective conditional knockout of Rac1 (Rac1-cKO). Rac1-cKO significantly reduced the frequency of AMPA receptor-mediated miniature excitatory postsynaptic currents, while glycine/GABA receptor-mediated miniature inhibitory postsynaptic currents were not affected. Although the total GluA1 protein level was increased in Rac1-cKO mice, its expression in the membrane component was unchanged. Rac1-cKO 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 Rac1 selectively affects excitatory synaptic transmission in RGCs by modulating dendritic complexity.

Increased CXCL13 and CXCR5 in Anterior Cingulate Cortex Contributes to Neuropathic Pain-Related Conditioned Place Aversion / 神经科学通报·英文版

Pain consists of sensory-discriminative and emotional-affective components. The anterior cingulate cortex (ACC) is a critical brain area in mediating the affective pain. However, the molecular mechanisms involved remain largely unknown. Our recent study indicated that C-X-C motif chemokine 13 (CXCL13) and its sole receptor CXCR5 are involved in sensory sensitization in the spinal cord after spinal nerve ligation (SNL). Whether CXCL13/CXCR5 signaling in the ACC contributes to the pathogenesis of pain-related aversion remains unknown. Here, we showed that SNL increased the CXCL13 level and CXCR5 expression in the ACC after SNL. Knockdown of CXCR5 by microinjection of Cxcr5 shRNA into the ACC did not affect SNL-induced mechanical allodynia but effectively alleviated neuropathic pain-related place avoidance behavior. Furthermore, electrophysiological recording from layer II-III neurons in the ACC showed that SNL increased the frequency and amplitude of spontaneous excitatory postsynaptic currents (sEPSCs), decreased the EPSC paired-pulse ratio, and increased the α-amino-3-hydroxy-5-methyl-4-isoxazolepropionic acid receptor/N-methyl-D-aspartate receptor ratio, indicating enhanced glutamatergic synaptic transmission. Finally, superfusion of CXCL13 onto ACC slices increased the frequency and amplitude of spontaneous EPSCs. Pre-injection of Cxcr5 shRNA into the ACC reduced the increase in glutamatergic synaptic transmission induced by SNL. Collectively, these results suggest that CXCL13/CXCR5 signaling in the ACC is involved in neuropathic pain-related aversion via synaptic potentiation.

Presynaptic Dysfunction by Familial Factors in Parkinson Disease / 대한배뇨장애요실금학회지

Parkinson disease (PD) is the second most prevalent neurodegenerative disorder after Alzheimer disease. The loss of specific brain area, the substantia nigra pars compacta is known as a major etiology, however it is not fully understood how this neurodegeneration is initiated and what precisely causes this disease. As one aspect of pathophysiology for PD, synaptic dysfunction (synaptopathy) is thought to be an earlier appearance for neurodegeneration. In addition, some of the familial factors cumulatively exhibit that these factors such as α-synuclein, leucine-rich repeat kinase 2, parkin, PTEN-induced kinase 1, and DJ-1 are involved in the regulation of synaptic function and missense mutants of familial factors found in PD-patient show dysregulation of synaptic functions. In this review, we have discussed the physiological function of these genetic factors in presynaptic terminal and how dysregulation of presynaptic function by genetic factors might be related to the pathogenesis of Parkinson disease.

Effect of bupivacaine on mEPSCs and mIPSCs of neurons in hippocampal CA1 region of rats / 中华麻醉学杂志

Objective To evaluate the effect of bupivacaine on miniature excitatory postsynaptic currents (mEPSCs) and miniature inhibitory postsynaptic currents (mIPSCs) of neurons in hippocampal CA1 region of rats. Methods Twenty SPF healthy male Sprague-Dawley rats, aged 4-6 weeks, weighing 300-350 g, were divided into control group ( C group, n=10) and bupivacaine model group ( BPV group, n=10) using a random number table method. The central nervous system toxicity model was established by infusing 0. 75％ bupivacaine at a rate of 1 mg·kg-1 ·min-1 via the tail vein in BPV group, while normal saline was infused for 7. 5 min at a rate of 1 mg·kg-1 ·min-1 via the tail vein in C group. Rats were sacri-ficed at 6 h after successful establishment of the model, the brains was removed and hippocampal slices were prepared. The whole-cell patch-clamp technique was used to record the frequency and amplitude of mEPSCs and mIPSCs. Results Compared with C group, the frequency of mIPSCs was significantly de-creased ( P<0. 01) , and no significant change was found in the amplitude of mEPSCs or frequency and am-plitude of mIPSCs in BPV group ( P>0. 05) . Conclusion The mechanism of bupivacaine-induced central nervous system toxicity is related to decreasing the frequency of mIPSCs in hippocampal neurons of rats.

Intravenous Anesthetic, Propofol Affects Synaptic Responses in Cerebellar Purkinje Cells

OBJECTIVE: Propofol is an intravenously administered anesthetic that enhances γ-aminobutyric acid-mediated inhibition in the central nerve system. Other mechanisms may also be involved in general anesthesia. Propofol has been implicated in movement disorders. The cerebellum is important for motor coordination and motor learning. The aim of the present study was to investigate the propofol effect on excitatory synaptic transmissions in cerebellar cortex. METHODS: Excitatory postsynaptic currents by parallel fiber stimulation and complex spikes by climbing fiber stimulation were monitored in Purkinje cells of Wister rat cerebellar slice using whole-cell patch-clamp techniques. RESULTS: Decay time, rise time and amplitude of excitatory postsynaptic currents at parallel fiber Purkinje cell synapses and area of complex spikes at climbing fiber Purkinje cell synapses were significantly increased by propofol administration. CONCLUSION: The detected changes of glutamatergic synaptic transmission in cerebellar Purkinje cell, which determine cerebellar motor output, could explain cerebellar mechanism of motor deficits induced by propofol.

Mechanism of spinal monocyte chemoattractant protein-1-mediated maintenance of chronic pathological pain in rats: the relationship with synaptic transmission in spinal dorsal horns / 中华麻醉学杂志

Objective To evaluate the relationship between the mechanism of spinal monocyte chemoattractant protein-1 (MCP-1)-mediated maintenance of chronic pathological pain and synaptic transmission in spinal dorsal horns of rats.Methods Female Sprague-Dawley rats,aged 2-3 weeks after birth,weighing 150-210 g,were studied.The experiment was performed in 2 parts.Experiment Ⅰ Eighteen Sprague-Dawley rats were randomly divided into 2 groups (n =9 each) on 7 days after intrathecal catheters were inserted:phosphate buffer solution (PBS) group and MCP-1 group.PBS 10 μl was intrathecally injected in group PBS,and PBS 10 μ1 containing 100 ng MCP-1 was intrathecally injected in group MCP-1.The mechanical pain threshold was measured at 30 and 60 min before intrathecal injection,and 30,60,90,120,150 and 180 min and 1,2 and 3 days after intrathecal injection.Experiment Ⅱ The transverse spinal cord slices were prepared,and substantia gelatinosa neurons were selected for whole-cell patch-clamp recording.Electrophysiological recording was performed at 1 h of incubation with artificial cerebrospinal fluid (ACSF) and immediately after adding MCP-1:for excitatory synaptic transmission recording,MCP-1 (final concentration 100 nmol/L),N-methyl-D-aspartate (NMDA,final concentration 100 μmol/L) and α-amino-3-hydroxy-5-methyl-4-isoxazole-propionic acid (AMPA,final concentration 20 μmol/L) were added to ACSF,and spontaneous excitatory postsynaptic currents (sEPSCs),AMPA receptors-mediated currents and NMDA receptors-mediated currents were recorded;for inhibitory synaptic transmission recording,MCP-1 (final concentration 100 nmol/L) and γ-aminobutyric acid (GABA,final concentration 1 mmol/L) were added to ACSF,and spontaneous inhibitory postsynaptic currents (sIPSCs) and GABA receptors-mediated currents were recorded.Results Compared with group PBS,the mechanical pain threshold was significantly decreased at 30 min-2 days after intrathecal injection in group MCP-1 (P＜0.01).Compared with those at 1 h of incubation with ACSF,the frequency and amplitude of sEPSCs were significantly increased,the amplitude of NMDA receptors-and AMPA receptors-mediated currents were increased,the frequency and amplitude of sIPSCs were decreased,and the amplitude of GABA receptors-mediated currents was decreased immediately after adding MCP-1 (P＜0.05).Conclusion MCP-1 enhances excitatory synaptic transmission through enhancing the function of NMDA and AMPA receptors in the posterior substantia gelatinosa neurons of the spinal cord;MCP-1 weakens inhibitory synaptic transmission through inhibiting GABA receptor function,which may be involved in MCP-l-mediated maintenance of chronic pathological pain in rats.

The Linear Transmission of the Vestibular Neural Information by Galvanic Vestibular Stimulation / 대한평형의학회지

OBJECTIVE: Growing hypotheses indicate the galvanic vestibular stimulation (GVS) as an alternative method to manage the symptoms of parkinson's disease (PD). GVS is easy and safe for use, and non-invasive. However, it is elusive how the neural information caused by GVS is transmitted in the central nervous system and relieves PD symptoms. To answer this question, we investigated the transmission of neural information by GVS in the central vestibular system, focused on vestibular nucleus (VN). METHODS: Twenty guinea pigs were used for this study for the extracellular neuronal recordings in the VN. The neuronal responses to rotation and GVS were analyzed by curve-fitting, and the numerical responding features, amplitudes and baselines, were computed. The effects of stimuli were examined by comparing these features. RESULTS: Twenty six vestibular neurons (15 regular and 11 irregular neurons) were recorded. Comparing the difference of baselines, we found the neural information was linearly transmitted with a reduced sensitivity (0.75). The linearity in the neural transmission was stronger in the neuronal groups with regular (correlation coefficient [Cor. Coef.]=0.91) and low sensitive units (Cor. Coef.=0.93), compared with those with irregular (Cor. Coef.=0.86) and high-sensitive neurons (Cor. Coef.=0.77). CONCLUSION: The neural information by GVS was linearly transmitted no matter what the neuronal characteristics were.

Response properties of neurons and synaptic plasticity during pre-critical period of visual development in mouse visual cortex / 中华实验眼科杂志

Background The visual development is completed during the critical period in human and mammals.However,the critical period is not the initial of receiving visual experience.It is known that before the onset of critical period in mammals,such as mouse,there is an earlier stage for visual development,the pre-critical period.The research of response characteristics of the visual cortical neurons and the synaptic plasticity in the pre-critical period is still in the exploratory stage.Objective The study aimed to preliminarily investigate the response properties of neurons and synaptic plasticity in mouse visual cortex during the pre-critical period.Methods Fortyeight postnatal day 13-17 C57BL/6J mice were used for in vivo whole-cell recordings and in vitro brain slice wholecell recordings.In vivo whole-cell recordings were done in anesthetized mice.Moving bars in different directions were produced and controlled by a Matlab program.Cell recordings were obtained at the depth of layer Ⅳ of visual cortex.Step current stimuli under current clamp were given to measure the membrane response properties of neurons.Optimal visual stimuli were given to measure the in vivo largest responses of membrane potentials.In vitro experiments were performed after in vivo experiments.All cells were given current step stimuli to measure the membrane response properties of neurons.Different intensities of white-matter-to-layer-Ⅳpathway stimulation were given to measure the evoked response properties.All cells from 48 mice were randomized into 4 groups according to different stimulus training modes,including low frequency stimulation (LFS),high frequency theta-burst stimulation (TBS),pre-post synaptic timing stimulation (pre-post TS) and post-pre synaptic timing stimulation (post-pre TS).Under the voltage clamp of-70 mV,excitatory postsynaptic currents (EPSCs) before and after training were recorded to measure the plastic changes of excitatory synaptic connections.pClamp 10 was used for the pre-analysis of data and Matlab 2008a was used for statistical analysis.The use and care of the animals followed the Statement for the Use of Animals in Ophthalmic and Vision Research.Results Thirty-nine cells and 48 cells were successfully recorded in the in vivo and in vitro experiments,respectively.The steady-state average number of action potentials (APs) were (1.01 ± 0.03)/sweep and (1.01 ±0.05)/sweep,the AP thresholds were (-40.2 ± 3.2) mV and (-39.6 ±2.0) mV,and the threshold step current levels were (126.7 ± 17.4) pA and (129.6 ± 17.5) pA in the in vivo and in vitro recordings,respectively,with no significant differences between them (APs:t =0.512,P =0.610;AP thresholds:t =-1.074,P =0.286;current levels:t =-0.776,P =0.440).Under the optimal visual or pathway stimulation,the average peak response of membrane potentials was (7.3 ±4.3)mV and (6.4±2.8)mV with rarely evoked APs in the in vivo and in vitro experiments,respectively,with no significant difference between them (t =1.234,P =0.221).Under the in vitro recording,the EPSCs before LFS were [(138.1 ±51.9)pA],which was significantly higher than that after LFS [(76.1 ± 34.8)pA] (t=4.437,P=0.001),but no significant differences were seen in EPSCs before and after TBS (t=-0.756,P=0.466).The EPSCs before and after pre-post TS were (122.4±62.2)pA and (78.5±46.7)pA,and those before and after post-pre TS were (131.9 ±48.0) pA and (74.3 ± 30.7) pA,showing significant differences between them (pre-post TS:t =3.558,P =0.004;post-pre TS:t =4.283,P =0.001).Conclusions The construction of fundamental neural circuits in layer Ⅳ of mouse visual cortex is completed during pre-critical period.However,the membrane responsive capability of neurons and the synaptic connections are in an immature state,and the evoked responses to visual pathway inputs are basically subthreshold.The strength of synaptic connections is depressed with low frequency stimulation or pre-post/post-pre synaptic timing stimulation,and kept unchanged with high frequency stimulation.The development of visual neural system of PSP in mouse presents different characteristics from CP.

Effect of dexmedetomidine on synaptic transmission in spinal dorsal horn of rats / 中华麻醉学杂志

Objective To evaluate the effect of dexmedetomidine on synaptic transmission in the spinal dorsal horn of rats.Methods Male Sprague-Dawley rats,aged 4-6 weeks,weighing 150-200 g,were used in the study.The lumbar enlargemnent segments of the spinal cord were harvested,and the parasagittal lumbosacral spinal cord slices with attached dorsal roots were prepared and incubated in artificial cerebro-spinal fluid.The whole-cell patch-clamp technique was used to record each index,and 4 spinal cord slices were selected and used for each index records.Experiment Ⅰ Dexmedetomidine was added cumulatively in concentration increments.Aδ and C fibers-mediated evoked excitatory postsynaptic currents (eEPSCs) were recorded before administration (baseline) and during perfusion with dexmedetomidine 4 and 10 μg/ml.Experiment Ⅱ The neurons innervated by Aδ and C fibers were selected,and Aδ and C fibers-mediated eEPSCs were recorded before administration (baseline),at 5 min of perfusion with yohimbine (alpha 2 adrenergic receptor antagonist) 2 μmol/L,and during continuous perfusion with yohimbine 2 μmol/L plus dexmedetomidine 4 μg/ml.Experiment Ⅲ The evoked excitatory postsynaptic potentials (eE-PSPs) and evoked inhibitory postsynaptic potentials (eIPSPs) were recorded before administration (baseline) and during perfusion with dexmedetomidine 4 μg/ml.Results Dexmedetomidine could dose-dependently inhibit Aδ and C fibers-mediated eEPSCs,dexmedetomidine could inhibit Aδ and C fibers-mediated eEPSPs and produced no effect on eIPSPs,and yohimbine could inhibit dexmedetomidine-induced inhibitory effect on eEPSCs.Conclusion The mechanism by which dexmedetomidine inhibits nociceptive information transmission in the spinal dorsal horn is related to inhibition of excitatory synaptic transmission through activating α2-adrenergic receptors,but not related to activation of inhibitory synaptic transmission in rats.

Relationship between astrocytes and consciousness formation / 中华麻醉学杂志

Astrocytes were traditionally be deemed as supportive cells in the central nervous system.However,recent researches proved astrocytes exerted more important neurophysiological functions,such as regulation of synaptic transmission and integration of neural information.This paper summarized the researches on the functions of astrocytes related to synaptic transmission and analyzed the new features of astrocyte excitability,the communication between neurons and astrocytes and the effect of general anesthetics on astrocytes.Based on these new findings,this paper also suggested the underlying relationship between astrocytes and the loss of consciousness during general anesthesia.

Análise do jitter com agulha concêntrica em pacientes com miastenia gravis autoimune adquirida / Concentric needle jitter analysis in patients with autoimmune acquired myasthenia gravis

A técnica de eletromiografia de fibra única (EMGFU), mediante análise do jitter, é o método neurofisiológico mais sensível para a confirmação do distúrbio da junção neuromuscular na miastenia gravis (MG). Os registros são tradicionalmente obtidos com agulha de fibra única, de alto custo e reutilizável. Por causa da necessidade atual do uso de material descartável, a agulha concêntrica vem sendo utilizada em substituição à agulha de fibra única. A técnica utilizada é semelhante, porém os potencias de ação para a análise do jitter são obtidos com eletrodo de agulha concêntrica (Eletromiografia de fibra única - jitter com agulha concêntrica, EMGFU-JAC). Contudo, os estudos são escassos e as metodologias utilizadas são heterogêneas com a utilização dessa agulha. OBJETIVOS: Este estudo tem por objetivo mensurar os valores de jitter obtidos com agulha concêntrica, no músculo Orbicularis Oculi, em sujeitos saudáveis e em pacientes com MG autoimune adquirida e avaliar a validade do método nas formas generalizada e ocular da doença. MÉTODOS: Foram estudados 20 sujeitos saudáveis, 20 pacientes com miastenia gravis forma generalizada (grupo MGG) e 13 com a forma ocular da doença (grupo MGO). A EMGFU-JAC foi realizada em todos os participantes, idealmente com 20 medidas de jitter em cada estudo. O jitter foi expresso como a média das diferenças consecutivas (MCD). Em todos os pacientes do estudo foram realizados o teste de estimulação repetitiva e dosagem sérica de anticorpo antirreceptor de acetilcolina (ac-AChR) no momento da análise do jitter. Nos pacientes soronegativos para ac-AChR, foi pesquisado o anticorpo antimúsculo específico tirosina-quinase (ac-MuSK). Foram definidos o limite superior da normalidade (LSN) para a média do MCD de cada estudo e para valores individuais de MCD. Os critérios de anormalidade foram: (1) média do MCD acima do LSN; ou (2) mais de 10% dos valores individuais de MCD acima do LSN. A definição do LSN para valores...

Single fiber electromyography (SFEMG) technique, through jitter analysis, is the most sensitive neurophysiological method for confirmation of neuromuscular junction disorder in myasthenia gravis (MG). Records are traditionally obtained with single fiber needle, which is reusable and has a high-cost. Due to the current need of using disposable material, concentric needle has been used to replace single fiber needle. The technique is similar, but the action potential for jitter analysis is obtained with concentric needle electrode (SFEMG - concentric needle jitter, SFEMG-CNJ). However, studies are scarce and methodologies used are heterogeneous with the use of this needle. OBJECTIVES: This study aims to measure jitter values obtained with concentric needle in the Orbicularis Occuli muscle in healthy subjects and in patients with autoimmune acquired MG and to assess the validity of the method in generalized and ocular forms of the disease. METHODS: 20 healthy subjects, 20 patients with generalized myasthenia gravis (GMG group) and 13 with the ocular form of the disease (OMG group) were studied. SFEMG-CNJ was performed on all participants, ideally with 20 jitter values in each study. Jitter was expressed as the mean consecutive difference (MCD). Repetitive nerve stimulation and serum acetylcholine receptor antibody (AChR-ab) were performed in all patients in the study, by the time of jitter analysis. Tyrosine kinase specific antibody muscle antibodies (MuSK-ab) were performed in AChR-ab negative patients. The upper limit of normality (ULN) for the mean MCD and for individual jitter values were defined. The abnormality criteria were: (1) mean MCD above ULN; or (2) more than 10% of individual jitter values above ULN. The definition of ULN for individual jitter values was based on the concept that two out of 20 jitter values above ULN are acceptable in a healthy muscle for voluntary contraction technique. Therefore, the ULN for the 18th highest...

Paeoniflorin inhibits functional responses of rat cerebellar Purkinje cells to acute hypoxia insult / 中国病理生理杂志

[ ABSTRACT] AIM:To investigate the effects of paeoniflorin ( Pae) on the functional responses induced by acute hypoxic insult in the rat cerebellar Purkinje cells ( PCs) .METHODS:The whole-cell patch clamp was used for the intra-cellular recording of PCs in the rat cerebellar slices to evaluate the changes of membrane potential, the excitability of PCs, and the parallel fibre ( PF)-PC excitatory postsynaptic currents ( EPSCs) upon acute hypoxic insult alone or with the pre-sence of Pae.RESULTS:PCs showed an initial hyperpolarization followed by brief depolarization and long lasting post-hy-poxia hyperpolarization after hypoxia exposure.Pae completely blocked hypoxia-induced hyperpolarization and decreased the amplitude and the duration of hypoxic depolarization.Hypoxia up-regulated the excitability of rat PCs.Pae didn’t show any significant effect on the hypoxia-induced hyperexcitability in PCs.Acute hypoxia induced long-term depression ( LTD) in rat cerebellar PF-PC EPSCs, and Pae partially reversed hypoxia-induced depression in PF-PC EPSCs.CONCLUSION:Pae significantly suppresses hypoxia-induced responses in rat PCs and probably increases the tolerance of rat PCs to acute hypoxia.

Effects of Modafinil on Behavioral Learning and Hippocampal Synaptic Transmission in Rats / 대한배뇨장애요실금학회지

PURPOSE: Modafinil is a wake-promoting agent that has been proposed to improve cognitive performance at the preclinical and clinical levels. Since there is insufficient evidence for modafinil to be regarded as a cognitive enhancer, the aim of this study was to investigate the effects of chronic modafinil administration on behavioral learning in healthy adult rats. METHODS: Y-maze training was used to assess learning performance, and the whole-cell patch clamp technique was used to assess synaptic transmission in pyramidal neurons of the hippocampal CA1 region of rats. RESULTS: Intraperitoneal administration of modafinil at 200 mg/kg or 300 mg/kg significantly improved learning performance. Furthermore, perfusion with 1mM modafinil enhanced the frequency and amplitude of spontaneous postsynaptic currents and spontaneous excitatory postsynaptic currents in CA1 pyramidal neurons in hippocampal slices. However, the frequency and amplitude of spontaneous inhibitory postsynaptic currents in CA1 pyramidal neurons were inhibited by treatment with 1mM modafinil. CONCLUSIONS: These results indicate that modafinil improves learning and memory in rats possibly by enhancing glutamatergic excitatory synaptic transmission and inhibiting GABAergic (gamma-aminobutyric acid-ergic) inhibitory synaptic transmission.

Remembering Obaid Siddiqi, a pioneer in the study of temperature-sensitive paralytic mutants in Drosophila.

Although Obaid Siddiqi’s major research focus in neurogenetics was on chemosensation and olfaction in Drosophila, he made seminal contributions to the study of temperature-sensitive paralytic mutants that paved the way for research that we and many other investigators have continued to pursue. Here we recount Siddiqi’s investigation and the impact it had on our own studies especially at a formative stage of our careers. We acknowledge our debt to Obaid Siddiqi and remember him fondly as an inspired and inspiring scientist, mentor, role model and human being.