Objective: To investigate the effects of IMPX977 on long term potentiation(LTP) at Schaffer collateralCA1 synapses in vitro and on methyl Cp G binding protein 2(Mecp2) expression in mice cortex and hippocampus.Methods...Objective: To investigate the effects of IMPX977 on long term potentiation(LTP) at Schaffer collateralCA1 synapses in vitro and on methyl Cp G binding protein 2(Mecp2) expression in mice cortex and hippocampus.Methods: Thirty-two C57 BL/6 mice were randomly divided into four groups: control, olive oil(vehicle),IMPX977 low(5 mg/kg) and high(15 mg/kg) groups. Mice were administrated every other day orally for two weeks. Extracellular recording technique in vitro was used to record the effects of IMPX977 on Schaffer collateral-CA1 LTP pathway in acute mice hippocampal slices. The Mecp2 protein expression level was detected by Western blotting.Results: Compared to the control group, vehicle did not alter the synaptic transmission in Schaffer collateral-CA1 synapses, however, IMPX977 at concentrations of 5 mg/kg and 15 mg/kg significantly enhanced f EPSP(field excitatory postsynaptic potential) slope in Schaffer collateral-CA1 pathway to(179.6 ± 17.8)% and(191.4 ± 21.4)%, individually 60 min after HFS, IMPX977 improved LTP induction significantly at Schaffer collateral-CA1 pathway at least. Also, IMPX977 significantly elevated Me CP2 protein level in cortex.Conclusion: The effects of IMPX977 on synaptic transmission and Mecp2 protein expression provided convincing evidence that IMPX977 could be promising new drug candidates for Rett syndrome treatment.展开更多
Learning-associated functional plasticity at hippocampal synapses remains largely unexplored. Here, in a single session of reward-based trace conditioning, we examine learning-induced synaptic plasticity in the dorsal...Learning-associated functional plasticity at hippocampal synapses remains largely unexplored. Here, in a single session of reward-based trace conditioning, we examine learning-induced synaptic plasticity in the dorsal CA1 hippocampus (dCA1). Local field-potential recording combined with selective optogenetic inhibition first revealed an increase of dCA1 synaptic responses to the conditioned stimulus (CS) induced during conditioning at both Schaffer collaterals to the stratum radiatum (Rad) and temporoammonic input to the lacunosum moleculare (LMol). At these dCA1 inputs, synaptic potentiation of CS-responding excitatory synapses was further demonstrated by locally blocking NMDA receptors during conditioning and whole-cell recording sensory-evoked synaptic responses in dCA1 neurons from naive animals. An overall similar time course of the induction of synaptic potentiation was found in the Rad and LMol by multiple-site recording;this emerged later and saturated earlier than conditioned behavioral responses. Our experiments demonstrate a cued memory-associated dCA1 synaptic plasticity induced at both Schaffer collaterals and temporoammonic pathways.展开更多
与会人员：CL Carly Lovejoy MiningMagazine BF Bob Fassl阿特拉斯·科普柯BS Ben Snyman久益国际DR David Rea卡特彼勒GK Geoff Knox通用电气IH Ivor Hill小松IM Iain McLean达索系统（Gemcom）JA Jay Armburger卡特彼勒JG Jim Ga...与会人员：CL Carly Lovejoy MiningMagazine BF Bob Fassl阿特拉斯·科普柯BS Ben Snyman久益国际DR David Rea卡特彼勒GK Geoff Knox通用电气IH Ivor Hill小松IM Iain McLean达索系统（Gemcom）JA Jay Armburger卡特彼勒JG Jim Gallagher Hatch KK Kimmo Kontola奥图泰MS Manfred Schaffer山特维克NB Norbert Becker西门子PF Peter Flanagan艾法史密斯PM Paul Martin利勃海尔WK Walter Kung特诺恩（接上期）PF在矿物加工方面,我想关于效率的见解更富有戏剧性。我们现在进行如此大的投资将低品位的矿石开采出来,经过加工获得如此少的金属。展开更多
基金Guangzhou Science Technology and Innovation Commission Technology Research Projects (No. 201805010005)Scientific Research Common Program of Beijing Municipal Commission of Education (No. KM201 100250)the National Natural Science Foundation of China (No. 81073137) for financial support of this project。
文摘Objective: To investigate the effects of IMPX977 on long term potentiation(LTP) at Schaffer collateralCA1 synapses in vitro and on methyl Cp G binding protein 2(Mecp2) expression in mice cortex and hippocampus.Methods: Thirty-two C57 BL/6 mice were randomly divided into four groups: control, olive oil(vehicle),IMPX977 low(5 mg/kg) and high(15 mg/kg) groups. Mice were administrated every other day orally for two weeks. Extracellular recording technique in vitro was used to record the effects of IMPX977 on Schaffer collateral-CA1 LTP pathway in acute mice hippocampal slices. The Mecp2 protein expression level was detected by Western blotting.Results: Compared to the control group, vehicle did not alter the synaptic transmission in Schaffer collateral-CA1 synapses, however, IMPX977 at concentrations of 5 mg/kg and 15 mg/kg significantly enhanced f EPSP(field excitatory postsynaptic potential) slope in Schaffer collateral-CA1 pathway to(179.6 ± 17.8)% and(191.4 ± 21.4)%, individually 60 min after HFS, IMPX977 improved LTP induction significantly at Schaffer collateral-CA1 pathway at least. Also, IMPX977 significantly elevated Me CP2 protein level in cortex.Conclusion: The effects of IMPX977 on synaptic transmission and Mecp2 protein expression provided convincing evidence that IMPX977 could be promising new drug candidates for Rett syndrome treatment.
基金supported by grants from the National Natural Science Foundation of China(31970957 and 31471078)the Shanghai Science and Technology Commission(19ZR1416600)a 2021-JCJQ-JJ-1089 fund.
文摘Learning-associated functional plasticity at hippocampal synapses remains largely unexplored. Here, in a single session of reward-based trace conditioning, we examine learning-induced synaptic plasticity in the dorsal CA1 hippocampus (dCA1). Local field-potential recording combined with selective optogenetic inhibition first revealed an increase of dCA1 synaptic responses to the conditioned stimulus (CS) induced during conditioning at both Schaffer collaterals to the stratum radiatum (Rad) and temporoammonic input to the lacunosum moleculare (LMol). At these dCA1 inputs, synaptic potentiation of CS-responding excitatory synapses was further demonstrated by locally blocking NMDA receptors during conditioning and whole-cell recording sensory-evoked synaptic responses in dCA1 neurons from naive animals. An overall similar time course of the induction of synaptic potentiation was found in the Rad and LMol by multiple-site recording;this emerged later and saturated earlier than conditioned behavioral responses. Our experiments demonstrate a cued memory-associated dCA1 synaptic plasticity induced at both Schaffer collaterals and temporoammonic pathways.
文摘与会人员：CL Carly Lovejoy MiningMagazine BF Bob Fassl阿特拉斯·科普柯BS Ben Snyman久益国际DR David Rea卡特彼勒GK Geoff Knox通用电气IH Ivor Hill小松IM Iain McLean达索系统（Gemcom）JA Jay Armburger卡特彼勒JG Jim Gallagher Hatch KK Kimmo Kontola奥图泰MS Manfred Schaffer山特维克NB Norbert Becker西门子PF Peter Flanagan艾法史密斯PM Paul Martin利勃海尔WK Walter Kung特诺恩（接上期）PF在矿物加工方面,我想关于效率的见解更富有戏剧性。我们现在进行如此大的投资将低品位的矿石开采出来,经过加工获得如此少的金属。
