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LTP of EPSP evoked by ipsilateral pericentral canal stimulation in neonatal rat spinal cord motoneurons in vitro

LTP of EPSP evoked by ipsilateral pericentral canal stimulat...

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第六届亚太神经科学联合会学术会议暨中国神经科学学会第十一届全国学术会议

作者： Lei ZHANG Huan SONG Wen QIN Yu-Han SHI Meng-Ya WANG Cell Electrophysiology Laboratory Wannan Medical College

Objective To explore the possible synaptic plasticity of excitatory synaptic transmission from ipsilateral pericentral canal(iP CC), a presumed site of "central pattern generator" of motor control, to motoneurons(MNs) in spinal cord. Methods The intracellular recordings were performed in MNs of spinal cord slices isolated from neonatal rats(8-14 days old) and the excitatory postsynaptic potentials(EPSPs) were mainly evoked by electrical stimulation of i PCC, iP CC-EPSPs. Long-term potentiation(LTP) was induced by the tetanic electrical stimulation(100 Hz, 50 pulses/train, duration 0.3～1.0 ms, 6 trains, main interval 10 seconds, 20～100 V) on i PCC. The analysis method of apparent receptor kinetics of EPSP(Acta Physiol Sin 2014, 66: 129) was used to monitor the apparent receptor kinetic properties of i PCC-EPSPs. Results In 27 MNs with i PCC-EPSPs, the tetanic electrical stimulation of i PCC enhanced the amplitude of i PCC-EPSPs to more than 120% of the baseline and the enlargement lasted longer than 30 min in 9 cells, which could be referred to as LTP(iP CC-LTP). During i PCC-LTP, apparent association rate constant(K1) increased, apparent dissociation rate constant(K2) and apparent equilibrium dissociation constant(KT) decreased only in 4 MNs. It was also observed that the induction of i PCC-LTP was facilitated by pretreatment of bicuculline(30 μM) and strychnine(1 μM), but the maintenance of i PCC-LTP was nullified by APV(30 μM and DNQX(1 μM). Conclusion These preliminary data show that the possible long-term synaptic plasticity is induced in i PCC intraspinal pathways onto MNs, which may be considered as a candidate of neural basis underlying the "central pattern generator" of motor control.

关键词： motoneuron excitatory postsynaptic potential long-term potentiation

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Neuronal representation of computation of saccadic errors in macaque lateral intraparietal cortex(LIP)

Neuronal representation of computation of saccadic errors in...

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第六届亚太神经科学联合会学术会议暨中国神经科学学会第十一届全国学术会议

作者： Yang Zhou Yining Liu Si Wu Haidong Lu Mingsha Zhang State Key Laboratory of Cognitive Neuroscience and Learning Beijing Normal University Institute of Neuroscience Shanghai Institutes for Biological SciencesChinese Academy of Sciences University of Chinese Academy of Sciences The First Affiliated Hospital of Zhengzhou University

Objective Two types of signals in the brain code the position of motor effectors, i.e., endogenous signals(e.g., corollary discharge) and exogenous signals(e.g., proprioception). During self-oriented movements, the internally generated signals predict the required future position of motor effectors, whereas the externally generated signals inform their real positions. It has been argued that the comparison/integration of these two types of signals play a crucial role in motor control, motor learning, self-recognition and spatial perception. However, despite knowing that the frontoparietal lobes are involved in such signal integration, the underlying neural mechanisms are largely unknown. Methods: To address this question, we studied the signal integration of eye position during saccadic eye movements. We recorded single neuron's activity from the macaque lateral intraparietal cortex(LIP) while the animals were performing oculomotor tasks. LIP is a node that is used to link visual and oculomotor systems, which plays crucial roles in visual attention, saccadic planning and related cognitive processing. Results: Here, we report the co-existence of the predictive and real eye position signals in LIP: neurons with pre- and postsaccadic response predict the required future eye position;neurons with late postsaccadic response represent the extraocular proprioceptive signals. Moreover, the persistent pre- and postsaccadic response neurons behave like a "subtraction operator" to measure the discrepancy between the two types of signals. Their post-operated activity level is highly correlated with the animal's behavioral performance, e.g., the higher the post-operated activity(reflecting the greater incongruence between internal and external signals), the larger the saccadic error(distance between saccade end points and saccadic target) and the higher the probability of making corrective saccades. Conclusion: The correlation between neural activity and the animals' behavioral

关键词： Motor error Internal signal External signal Signal comparison Lateral Intraparietal Area(LIP)

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Effects of central N-type calcium channel on noradrenaline transmitter release from locus coeruleus projecting to hypothalamus in stress induced hypertension rats

Effects of central N-type calcium channel on noradrenaline t...

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第六届亚太神经科学联合会学术会议暨中国神经科学学会第十一届全国学术会议

作者： Jun-Tong Wu Wan-Kun Gong Zhao-Jun Xia Feng Wang Meng-Ya Wang Hong-Ping Huang Department of physiology and neurobiology Wannan medical college Department of Forensic medicine Wannan medical college

The present study is to study the dynamic characteristics of norepinephrine(NE) release in hypothalamus followed by electrical stimulation in locus coeruleus in the rat model of stress-induced hypertension(SIH) and explore the role of central N-type calcium channel in the pathogenesis of SIH. Male Sprague-Dawley rats(180～200g) were randomly divided into control and SIH groups. The SIH model rats were established by combining noise and foot-shock stresses. After the end of modeling, NE release in the hypothalamus by electrical stimulation in locus coeruleus was studied and NE signal was recorded by carbon fiber electrode. The peak value, the time to peak and half-life period of NE signal in both group rats were analyzed. Blood pres sure and the peak value of NE signal in the hypothalamic followed by electrical stimulation in locus coeruleus in SIH rats were more than in controls(P<0.05). Intracerebroventricular administration of ralfinamide messylate(sodium and N-type calcium channel blocker, i.c.v. 10μg) inhibited NE release in the hypothalamus in SIH rats and decreased blood pressure(P<0.05), whereas the effect of ralfinamide messylate was weak in control group rats. Otherwise, the blood pressure still has significant difference between two group rats after ralfinamide messylate treatment, but the significant difference of peak value of NE signal between two group rats was absent after ralfinamide messylate treatment. These findings suggest that combining noise and foot-shock stresses increased the secretion of NE in the hypothalamus followed by electrical stimulation in locus coeruleus in rats. Central N-type calcium channel contributes to NE release in hypothalamus and blood pressure modulation in SIH rats.

关键词： central N-type calcium channel locus coeruleus stress induced hypertension amperometry noradrenaline

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Interleukin 6 regulates iron related proteins through c-Jun N-terminal kinase activation in BV2 microglial cell lines

Interleukin 6 regulates iron related proteins through c-Jun ...

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第六届亚太神经科学联合会学术会议暨中国神经科学学会第十一届全国学术会议

作者： Jun Wang Shida Zhou Junxia Xie Department of Physiology Shandong Provincial Key Laboratory of Pathogenesis and Prevention of Neurological Disorders and State Key Disciplines: PhysiologyMedical College of Qingdao University

Parkinson's disease(PD) is a common neurodegenerative disorder characterized by the loss of dopaminergic(DA) neurons in the substantia nigra(SN) and the subsequent DA depletion in the striatum. Extensive studies have demonstrated that microglia activation and nigral iron accumulation play a key role in the pathogenesis of PD. The activated microglia showed amplified levels of iron deposit, however, the relationship between microglia activation and iron accumulation was not fully elucidated. In the present study, we aimed to investigate how the iron level affects interleukin-6(IL-6) synthesis in BV2 microglia, as well as the effect of IL-6 on cellular iron metabolism in BV2 microglia. The results were as follows: IL-6 m RNA was up-regulated after FAC treatment for 12 h in BV2 cells. Iron regulatory protein 1(IRP1) was up-regulated and iron exporter ferroportin1(FPN1) was down-regulated after IL-6 was treated for 24 h in BV2 cells. Phosphorylated c-Jun N-terminal kinase(JNK) increased significantly after IL-6 was treated in BV2 cells for 1 h compared with the control. Pretreatment with JNK inhibitor SP600125 attenuated the up-regulation of IRP1 and down-regulation of FPN1 compared with IL-6 treated group in BV2 cells. The results suggest that iron load can increase IL-6 m RNA expression in BV2 cells. IL-6 up-regulates IRP1 expression and down-regulates FPN1 expression in BV2 microglial cells through JNK signaling pathways.

关键词： microglia interleukin 6 iron regulatory protein 1 ferroportin 1 JNK

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TRPC6 specifically interacts with APP to inhibit its cleavage by γ-secretase and reduce Aβ production

TRPC6 specifically interacts with APP to inhibit its cleavag...

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第六届亚太神经科学联合会学术会议暨中国神经科学学会第十一届全国学术会议

作者： Junfeng Wang Rui Lu Jian Yang Hongyu Li Zhuohao He Naihe Jing Xiaomin Wang Yizheng Wang Laboratory of Neural Signal Transduction Institute of NeuroscienceSIBSGraduate School of Chinese Academy of Sciences State Key Laboratory of Neuroscience Graduate School of Chinese Academy of Sciences Department of Physiology and Neurobiology Capital Medical UniversityKey Laboratory for Neurodegenerative Disorders of the Ministry of Education State Key Laboratory of Cell Biology Institute of Biochemistry and Cell BiologySIBSChinese Academy of Sciences Beijing Key Laboratory of Mental Disorders Beijing Anding HospitalCapital Medical University Beijing Institute for Brain Disorders

Accumulation of β-amyloid(Aβ) peptide is critical for the pathogenesis of Alzheimer's disease. Generation of Aβ involves cleavage of amyloid precursor protein(APP) by γ-secretase, a protease known to cleave several substrates, including Notch. Attempts to treat AD patients by inhibiting γ-secretase activity have been disappointing. Finding specific modulators for γ-secretase could be another avenue to treat the disease. Here, we report that transient receptor potential canonical(TRPC) 6 specifically interacts with APP leading to inhibition of its cleavage by γ-secretase and reduction in Aβ production. Downregulating TRPC6 increased Aβ formation, while overexpressing TRPC6 suppressed γ-secretase cleavage of APP, but not that of Notch, and inhibited Aβ generation. TRPC6 interacted with APP(C99), but not with Notch, and prevented C99 interaction with presenilin 1(PS1). A fusion peptide derived from TRPC6 also reduced Aβ levels without effect on Notch cleavage. Crossing APP/PS1 mice with TRPC6 transgenic mice led to a marked reduction in both plague load and Aβ levels, and improvement in structural and behavioral impairment. Thus, TRPC6 specifically modulates γ-secretase cleavage of APP and preventing APP(C99) interaction with PS1 via TRPC6 could be a novel strategy to reduce Aβ formation.

关键词： TRPC6,Aβ,γ-secretase,Alzheimer's disease

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Ascorbic acid improves axonal regeneration and remyelination after peripheral nerve injury

Ascorbic acid improves axonal regeneration and remyelination...

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第六届亚太神经科学联合会学术会议暨中国神经科学学会第十一届全国学术会议

作者： Yuan-Yuan Li Li-Xia Li Jin-Kun Wen Meng-Jie Pan Xiang-Hai Wang Chang-Hui Qian Yi-Jing Chen Jia-Song Guo Department of Histology and Embryology Southern Medical University Key Laboratory of Tissue Construction and Detection of Guangdong Province

Ascorbic acid(also is called as Vitamin C) which is an essential nutrient for humans and certain other animal species, has lots of important biological effects. It has been widely used for treating and preventing of scurvy and common cold, and also is advocated to treat asthma, atherosclerosis, wounds, schizophrenia, and cancer. Recent studies on Charcot-Marie-Tooth disease animal models indicated ascorbic acid may play important roles in demyelination/remyelination. However, no evidence has shown whether ascorbic acid is involved in the progress of axonal regeneration and remyelination after peripheral nerve injury. Herein, we prepared a standardized sciatic nerve crush model in mice and fed the mice with ascorbic acid(200mg/kg body weight) for 28 day. Then, behaviour test, electrophysiologic analysis, immmunohistology and transmission electron microscopy(TEM) were performed to detect the functional recovery, axonal regeneration and remyelination of the injured sciatic nerve. Compared with the saline treated control group, mice in ascorbic acid treated group exhibited better motor function recovery in the foot print test, have higher amplitude and shorter latency in compound muscular action potential(CMAP) electrophysiologic assay. Immunohistologic and TEM assessments also showed the number of regenerated axons and the thickness of new formed myelin were significantly increased in the ascorbic acid treated sciatic nerves. Overall results of current study indicated ascorbic acid has prospective potential to improve the axonal regeneration and remyelination, which may lead to novel therapeutic strategy for treating peripheral nerve injuries.

关键词： ascorbic acid,peripheral nerve injury,axonal regeneration,remyelination

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Convergent integration of various local orientations to form a global orientation from V1 and V2 to V4 in macaque

Convergent integration of various local orientations to form...

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第六届亚太神经科学联合会学术会议暨中国神经科学学会第十一届全国学术会议

作者： Zhe-Yuan Chen Ye Liu Jia-Peng Yin Yi-Liang Lu Hong-Liang Gong I.M.Andolina Xiao-Hong Li Wei Wang Institute of Neuroscience Chinese Academy of Science

A central question in vision is how the cortex integrates local cues to form global representations along the visual hierarchy. Orientation is a key feature of a given contourand the generation of orientation selectivity offers a great window to explore the neural mechanisms underlying visual information integration. The orientation selectivity in V4 is believed to be inherited through successive convergent projections from V1 and V2 neurons with the same orientation preference. However, for a stimulus like the zebra crossing, what happens when the global orientation and the local orientations are not matched? We investigated this question of orientation integration by simultaneous optical imaging of V1, V2, and V4 and subsequent single-unit recordings in anesthetized and awake macaques, respectively. We found that for a given orientation stimulus, the orientation domains in V1, V2, and V4 all exhibited the same orientation preference to the stimulus. However, for a global orientation stimulus defined by different local orientations, only V4 encoded the global orientation whiles V1 and V2 signaled the local orientations, suggesting V4 can integrate feed-forward inputs from V1/V2 with different orientation preferences. These population results were later confirmed by electrophysiological recordings as 85% neurons in V4, in contrast to only 28% neurons in V2 and few neurons in V1, encoded the global orientation of such stimuli. Our results demonstrate that V4 orientation domain integrates feed-forward inputs not only from V1/V2 orientation columns with the same preference, but also from those with different preferences. Our findings thus reveal the orientation integration from local into global across different visual cortices

关键词： Local and global orientations Cortical integration Orientation selectivity

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p38 MAPK participates in the up-regulation of GLT-1 during the induction of brain ischemic tolerance by cerebral ischemic preconditioning

p38 MAPK participates in the up-regulation of GLT-1 during t...

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第六届亚太神经科学联合会学术会议暨中国神经科学学会第十一届全国学术会议

作者： Min Zhang Jian-Xue Gong Jia-Lei Wang Meng-Yang Jiang Li Li Hang Zhao Yu-Yan Hu Wen-Bin Li Department of Pathophysiology Hebei Medical University

Our previous study has proved that the up-regulation of glial glutamate transporter 1(GLT-1) induced by cerebral ischemic preconditioning(CIP) played an important role in the acquisition of brain ischemic tolerance in rats. However, little is known about the mechanism involved in the up-regulation of GLT-1 induced by CIP. The present study investigates whether p38 MAPK, ERK1/2, and/or JNK participates in the up-regulation of GLT-1 during the induction of brain ischemic tolerance by CIP. We found that CIP significantly enhanced the expression of p-p38 MAPK without altering p-ERK1/2 and p-JNK expression in the CA1 hippocampus. Importantly, inhibiting p38 MAPK function by SB203580, a selective inhibitor of p38 MAPK, or decreasing p38 MAPK expression by its antisense oligodeoxynucleotides(AS-ODNs) inhibited the induction of brain ischemic tolerance by CIP. The above indicated that p38 MAPK participates in the induction of brain ischemic tolerance by CIP. Furthermore, p38 MAPK was activated earlier than the up-regulation of GLT-1 in the CA1 hippocampus in rats after CIP. At the same time, the expression of p-p38 MAPK by astrocytes was increased using double immunofluoresence for p-p38 MAPK and glial fibrillary acidic protein(GFAP), a specific protein expressed by astrocytes, and p38 MAPK AS-ODNs dose dependently inhibited the up-regulation of GLT-1 in the CA1 hippocampus after CIP. Taken together, it could be concluded that p38 MAPK participates in mediating the up-regulation of GLT-1 during the induction of brain ischemic tolerance by CIP.

关键词： p38 MAPK glial glutamate transporter-1 brain ischemic tolerance cerebral ischemic preconditioning hippocampus rat

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The role of V1 in visual stimulus contrast detection and external noise exclusion

The role of V1 in visual stimulus contrast detection and ext...

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第六届亚太神经科学联合会学术会议暨中国神经科学学会第十一届全国学术会议

作者： Qian Wang Jin-Fang Yang Sang Jiang Cai-Hong Jin Rui-Long Liu Tian-Miao Hua College of Life Sciences Anhui Normal University

Objective Visual perception depends on the ability of visual system,especially the visual cortex, in detecting visual signals and excluding external noise. However, the relative contribution of different cortical areas to these functions remains unclear. This study tried to assess the role of primary visual cortex(V1) in the detection of stimulus contrast and exclusion of external noise added in the stimuli. Methods we trained 3 cats to discriminate between vertical and horizontal grating stimuli for conditioning training using 2-AFC method, and then measured the stimulus contrast threshold needed for cats to identify the visual stimuli masked by different level of external noise contrast(6 level: 0, 0.1, 0.2, 0.4, 0.6, 0.8), so as to construct psychophysical TvC(stimulus contrast threshold versus noise contrast) functions. Subsequently, We examined systematically the response of V1 neurons to different stimulus contrast under different levels of noise contrast using in vivo single-unit recording techniques. ROC(receiver operating characteristics) analysis was used to acquire the stimulus contrast threshold needed for V1 neurons to detect visual stimuli masked by different noise contrast, so as to build neuronal TvC functions. Results 1) The stimulus contrast threshold needed for 3 cats to identify visual stimuli increased with noise contrast levels added in the visual stimuli. 2) The stimulus contrast threshold needed for V1 neurons to detect visual stimuli also increased with noise levels in each cat. 3) At the low noise levels, the neuronal contrast threshold was quite close to psychophysical contrast threshold. However, with increasing noise, the neuronal contrast threshold was greatly higher than psychophysical one. Conclusion Neurons in V1 may play a major role in visual signal contrast detection, but contribute slightly to noise exclusion in visual signals.

关键词： Primary visual cortex,Visual stimuli,Contrast detection,External noise exclusion

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The coupling interface and pore domain codetermine the single-channel activity of the α7 nicotinic receptor

The coupling interface and pore domain codetermine the singl...

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第六届亚太神经科学联合会学术会议暨中国神经科学学会第十一届全国学术会议

作者： Jun-jun Zhao Jing Qu Yuan Zheng Hui Yang Jian-liang Zhang Department of Neurobiology Beijing Institute of Brain DisordersCapital Medical UniversityKey Laboratory for Neurodegenerative Disease of the Ministry of EducationBeijing Center of Neural Regeneration and RepairBeijing Key Laboratory of Brain Major Disorders-State Key Lab Incubation BaseBeijing Neuroscience Disciplines

Objective Ligand-gated ion channels play a role in mediating fast synaptic transmission for communication between neurons. However, the structural basis for the functional coupling of the binding and pore domains, resulting in channel opening, remains a topic of intense investigation. Methods Here, a series of α7 nicotinic receptor mutants were constructed for expression in cultured mammalian cells, and their single-channel properties were examined using the patch-clamp technique combined with radio ligand binding and the fluorescence staining technique. Results We demonstrated that the replacement of the four pore-lining residues in the channel domain of the α7 nicotinic receptor with the hydrophilic residue serine prolongs the open-channel lifetime, although the conductance of these mutants decreases. At the coupling interface between the extracellular and transmembrane domains, when the VRW residues in the Cys-loop were substituted with the corresponding residues(i.e., IYN) in the 5-HT3 A receptor, thesingle-channel activity elicited by acetylcholine is impaired. This effect occurred despite the expression of the mutant receptors on the cell surface and despite the fact that the apparent Kd values were much lower than those of the wild-type α7 receptor. When we further lowered the channel-gating barrier of this chimera to enhance the open-channel probability, the loss of function was rescued. Conclusion Overall, we explored the microscopic mechanisms underlying the interplay between the channel domains and the coupling interface that affect the channel activity, and we generated an allosteric gating model for the α7 receptor. This model shows that the gating machinery and coupling assembly codetermine the single-channel gating kinetics. These results likely apply to all channels in the Cys-loop receptor family.

关键词： The coupling interface and pore domain codetermine the single-channel activity of the nicotinic receptor domain

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