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Gestational dexamethasone exposure impacts hippocampal excitatory Synaptic transmission and learning and memory function with transgenerational effects

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药学学报:英文版 2023年第9期13卷 3708-3727页

作者： Mingcui Luo Yiwen Yi Songqiang Huang Shiyun Dai Lulu Xie Kexin Liu Shuai Zhang Tao Jiang Tingting Wang Baozhen Yao Hui Wang Dan Xu Department of Obstetrics Zhongnan Hospital of Wuhan UniversitySchool of Pharmaceutical SciencesWuhan UniversityWuhan 430071China Department of Pharmacology Taikang Medical School(School of Basic Medical Sciences)Wuhan UniversityWuhan 430071China Hubei Provincial Key Laboratory of Developmentally Originated Disease Wuhan 430071China Department of Pediatrics Renmin Hospital of Wuhan UniversityWuhan 430071China Department of Pharmacy Zhongnan Hospital of Wuhan UniversityWuhan 430071China

The formation of learning and memory is regulated by synaptic plasticity in hippocampal neurons.Here we explored how gestational exposure to dexamethasone,a synthetic glucocorticoid commonly used in clinical practice,has lasting effects on offspring's learning and memory.Adult offspring rats of prenatal dexamethasone exposure(PDE)displayed significant impairments in novelty recognition and spatial learning memory,with some phenotypes maintained transgenerationally.PDE impaired Synaptic transmission of hippocampal excitatory neurons in offspring of F1 to F3 generations,and abnormalities of neurotransmitters and receptors would impair synaptic plasticity and lead to impaired learning and memory,but these changes failed to carry over to offspring of F5 and F7 generations.Mechanistically,altered hippocampal miR-133a-3p-SIRT1-CDK5-NR2B signaling axis in PDE multigeneration caused inhibition of excitatory Synaptic transmission,which might be related to oocyte-specific high expression and transmission of miR-133a-3p.Together,PDE affects hippocampal excitatory Synaptic transmission,with lasting consequences across generations,and CDK5 in offspring's peripheral blood might be used as an early-warning marker for fetal-originated learning and memory impairment.

关键词： Dexamethasone Early-warning marker Hippocampus Histon acetylation Learning and memory impairment MicroRNA Synaptic transmission Transgenerational inheritance

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In vivo Synaptic transmission in the zebra finch high vocal center and robust nucleus of the arcopallium after different stimulus patterns

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Neural Regeneration Research 2008年第5期3卷 472-477页

作者： Suqun Liao Wenxiao Liu Peng Xiao Dongfeng Li College of Life Sciences South China Normal University Guangzhou 510631 Guangdong Province China

BACKGROUND： Electrophysiological studies using brain slices have revealed that the developmental regulation of synaptic plasticity in vocal learning pathway is essential for song learning in zebra finches. Publications reporting in vivo electrophysiological investigation are scarce. Many aspects of neural mechanisms underlying song learning and production still remain uncertain. OBJECTIVE： To observe the efficacy of paired pulses and the effect on Synaptic transmission induced by low-frequency stimulations, high-frequency stimulations, and theta-burst stimulations. DESIGN, TIME AND SETTING： A comparative observation. The experiment was conducted from October 2006 to October 2007 in the Neurophysiology Laboratory of South-China Normal University. MATERIALS： Twenty-four adult male zebra finches were supplied by the Department of Animal Experiment of College of Life Sciences, South China Normal University. A SEN-7203 stimulator （NIHON KOHDEN）, as well as a DSJ-731WF microelectrode amplifier and DSJ-F amplifier （provided by South-China Normal University）, were used to stimulate and record, respectively. METHODS： Animals were randomly divided into low-frequency, high-frequency, and theta-burst frequency stimulation groups. After recording evoked potentials, an input-output curve was evaluated. Subsequently, the efficacy of paired pulses with different stimulus intensity （1/3, 1/2, 2/3, or 3/4 of the value that induced the largest synaptic response）, as well as interpulse intervals （50, 75, and 100 ms）, was measured in each group. The test stimulus intensity was set to a level that evoked 1/2 or 1/3 amplitude of the maximum response. MAIN OUTCOME MEASURES： Changes in amplitude, slope, and area of evoked potentials elicited by different stimulus patterns. RESULTS：（1） Efficacy of paired pulses： there was significant paired-pulse facilitation in the high vocal center and robust nucleus of the arcopallium （HVC-RA） synapse. Efficacy decreased when paired-pulse intervals or stimulus intensities were increased. （2） Low-frequ

关键词： electrical stimulus patterns Synaptic transmission in vivo zebra finch

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Uncovering the roles of CAST/ELKS protein family in the regulation of Synaptic transmission and plasticity

Uncovering the roles of CAST/ELKS protein family in the regu...

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中国神经科学学会第十二届全国学术会议

作者： Wei Dong Monica Montesinos Matthias Lübbert R.Oliver Goral Travis Putzke Kevin Goff Debbie Guerrero-Given Akari Hagiwara Maya Yamazaki Manabu Abe Kenji Sakimura Naomi Kamasawa Toshihisa Ohtsuka Samuel M.Young,Jr Key Laboratory of Medical Electrophysiology Ministry of Education Collaborative Innovation Center for Prevention and Treatment of Cardiovascular Disease/Institute of Cardiovascular Research Southwest Medical University

Synapses utilize a network of proteins, the cytomatrix at the active zone(CAZ) to tightly regulate synaptic strength and SV release kinetics to match the changing needs of the neuronal circuit. The CAST/ELKS family, central components of the CAZ, have been implicated as key proteins that regulate synaptic function. However, their functional roles in the regulation of neuronal circuits remain unresolved. Using a newly created CAST KO/ELKS conditional KO mouse line which overcomes the embryonic lethality associated with constitutive KO of ELKS proteins, we analyzed the role of the CAST/ELKS protein family in regulation of presynaptic function to match the needs of the neuronal circuit. To do so, we utilized the calyx of Held, a large excitatory presynaptic terminal located in the auditory brainstem and the dominant input for driving postsynaptic spiking in the Medial Nucleus of the trapezoid body(MNTB) to help encode sound information. We carried out electrophysiological and ultrastructural analysis in both the immature(prehearing postnatal day,(P9-11) and functionally mature(hearing, P16-P21) calyx to elucidate the roles of the CAST/ELKS proteins. Here we identify for the first time, that the CAST/ELKS protein family regulates voltage gated Ca channel abundance in the presynaptic terminal. In addition, loss of CAST/ELKS proteins did not affect basal Synaptic transmission. However, loss of CAST/ELKS resulted in increased release probability while decreasing the size of the RRP available for action potential mediated release in the functionally mature calyx. Therefore, we conclude that the CAST/ELKS proteins are critical molecules that differentially control key parameters of synaptic function in response to the changing neuronal circuit demand.

关键词： calyx of Held Synaptic transmission plasticity pre-synaptic terminal CAST/ELKS

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SUMO1 Conjugation of Neuronal Nitric Oxide Synthase is required for Long-Term Potentiation of Synaptic transmission

SUMO1 Conjugation of Neuronal Nitric Oxide Synthase is requi...

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中国神经科学学会第十二届全国学术会议

作者： Cai-Ping DU Mei WANG Bin HU Chi GENG Dan-Dan WANG Yan XU Li MENG Xiao-Yu HOU Jiangsu Key Laboratory of Brain Disease Bioinformation Xuzhou Medical University Research Center for Biochemistry and Molecular Biology Xuzhou Medical University

Objective synaptic plasticity refers to the variability of synaptic structure and function. The long-term potentiation（LTP）, one manifestation of synaptic function plasticity, is considered as the cellular physiological basis for learning and memory. Nitric oxide（NO） functions as a retrograde neurotransmitter at the synapse and contributes to the coincident activity of pre-and post-synaptic neurons following LTP induction, which is generated mainly by neuronal NO synthase（nNOS） in the brain. Although nNOS has been proved to be responsible for LTP induction and fear memory, mechanisms underlying the dynamic regulation of nNOS-NO pathway remain to be well defined. Methods The SUMOylation of nNOS was detected by immunoprecipitation followed by immunoblot. The nNOS activity was measured by NO synthase determination kit. Standard excitatory postsynaptic potential（EPSP） were recorded in the hippocampus CA1 region. Results We identify nNOS as a target protein for reversible SUMOylation following synaptic activity alteration. synaptic activity enhancement induces SUMO1 attachment with postsynaptic nNOS in rat hippocampus, while synaptic activity inhibition induces de-SUMOylation of nNOS. Moreover, SUMO1 conjugation upregulates nNOS activity, and facilitates the plasticity-related protein BDNF expression. Disrupted nNOS SUMOylation impairs the LTP induction. Conclusion These findings indicate that nNOS SUMOylation is responsible for LTP of Synaptic transmission, providing a molecular and cellular signaling basis for postsynaptic regulation of activitydependent synaptic plasticity by SUMOylation.

关键词： SUMO1 neuronal nitric oxide synthase long-term potentiation Synaptic transmission

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Cannabinoid CB1 receptor signaling dichotomously modulates excitatory and inhibitory Synaptic transmission in rat inner retina

Cannabinoid CB1 receptor signaling dichotomously modulates e...

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中国神经科学学会第十届全国学术会议

作者： Xiao-Han Wang Yi Wu Xiao-Fang Yang Yanying Miao Ling-Dan Dong Xiong-Li Yang Zhongfeng Wang Institutes of Brain Science Institute of Neurobiology and State Key Laboratory of Medical NeurobiologyFudan University

In the inner retina,a neuronal circuit formed by ganglion cells（RGCs）,amacrine cells（ACs） and bipolar cells（BCs） integrates and modulates visual information.We investigated how activation of the cannabinoid CB1receptor（CB1R）,expressed on the terminals of ACs and BCs,as demonstrated by multiple labeling immunohistochemistry,regulates mTPSCs and mEPSCs of RGCs in rat retina.WIN55121-2（WIN）,a CB1R agonist,suppressed mTPSCs of RGCs by inhibiting L-type calcium channels of ACs.In contrast,the existence of inhibitory inputs from ACs to BCs was indispensable for WTN-induced suppression of mEPSCs of RGCs.Furthermore,the depolarized membrane potential of BCs in the absence of inhibitory inputs from ACs inactivated the T-type calcium channel that was responsible for the generation of RGC mEPSCs,so mat this channel could not be regulated.When the inactivation was eliminated by the hyperpolarization caused by the inhibitory inputs,the T-type channel was inhibited by activation of presynaptic CBlRs on BCs,which resulted in the suppression of the mEPSCs.This unique feature of CB lR-mediated retrograde regulation provides a novel mechanism for modulating excitatory Synaptic transmission in the inner retina.

关键词： cannabinoid CB1 receptor inner retina Synaptic transmission mEPSCs mIPSCs T-type calcium channel retinal ganglion cell

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Peroxynitrite as modulator effects on Synaptic transmission in rat hippocampal CA1 neurons

Peroxynitrite as modulator effects on synaptic transmission ...

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中国神经科学学会第九届全国学术会议暨第五次会员代表大会

作者： Yong-Ling XIE,Zhao-Wei LIU,Zhuo YANG~* School of Medicine,Nankai University,Tianjin 300071,China

Objective Peroxynitrite(ONOO),which formed in vivo under the oxidative stress in a diffusioncontrolled reaction between nitric oxide(NO)and superoxide anion,is a strong oxidizing and nitrating agent to mediate much of the toxicity of NO.It has been suggested that this kind of deleterious reactive nitrogen species(RNS) was involved in the development of a variety of pathological conditions such as the neurodegenerative disorders with disrupted memory and impaired cognition.The aim of this study was to investigate actions of ONOCT on Synaptic transmission in hippocampal CA1 neurons of Wistar rats.Methods Using patch clamp methods,we made the recording of NMDA-mediated miniature glutamatergic excitatory postsynaptic currents(mEPSC)and AMPA-mediated mEPSC in the hippocampal neurons in CA1 area of Wistar rats.Results Our results demonstrated that SIN-1 (3-morpholino-sydnonimine),used as the donor of ONOO,induced a bidirectional modulation of glutamatergic transmission under different concentrations.A high dose(1 mM)of SIN-1 decreased amplitudes of both NMDA-and AMPA-mediated mEPSC,mainly through altering the NMDA-mEPSC.And lower dose(100 uM)of SIN-1 caused a consistent increase in amplitudes of AMPA-and NMDA-mediated mEPSC,but depressed the frequencies. Additionally,co-treatment with SIN-1 and uric acid,a perxynitite scavenger,had no effects on mEPSC.Conclusion The results suggested that perxynitite could induce neurotoxicity through modulating excitatory transmitter release in both presynaptic and postsynaptic ways and play a role in the modification of synaptic function in hippocampal CA1 neurons.

关键词： peroxynitrite Synaptic transmission hippocampus slice

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Facilitating Synaptic transmission of （-）clausenamide in CA1 region of hippocampal slices by activating CaMKIIa

Facilitating synaptic transmission of （-）clausenamide in C...

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中国神经科学学会第九届全国学术会议暨第五次会员代表大会

作者： Jin-Feng HU,Na Ning,Yu-He YUAN,Jun-Tian ZHANG,Nai-Hong CHEN~* Key Laboratory of Bioactive Substances and Resources Utilization,Ministry of Education,Department of Pharmacology,Institute of Materia Medica,Chinese Academy of Medical Sciences and Peking Union Medical College,Beijing 100050,China

＜正＞Objective Effect of（-）clausenamide on potentiating field excitatory postsynaptic potential（f-EPSP）in CA1 region of rats’ hippocampal slice and its related mechanism were investigated in the paper.Methods 8×8 multi-electrode array probe was used to measure f-EPSP.The phosphorylation and expression of CaMKIIα,ERK1/2, CREB were detected by Western blot.Results（-）Clausenamide facilitated synaptic plasticity at dose-dependent manner.And（-）clausenamide also activated CaMKIIa and ERK1/2.Pretreatment with KN93（CaMKIIa inhibitor, 10μM）for 20 min before（-）clausenamide addition completely blocked the enhancement of synaptic transimisson induced by（-）clausenamide.PD98059（MEK inhibitor,30μM）partially blocked the effect of（-）clausenamide.And KN93 and PD98059 attenuated the activation of CREB induced by（-）clausenamide.Thus,the results suggested that CaMKIIα-ERKl/2-CREB involved in the process of（-）clausenamide facilitating Synaptic transmission.U73122,an inhibitor of PLCγ,attenuated the slop of f-EPSP before or after the treating of（-）clausenamide.Nimodipine blocked partially the effect of（-）clausenamide by pre-incubation,but showing no difference with basic value when treated after the perfusion of（-）clausenamide.The data indicated that external calcium influx induced by（-）clausenamide was necessary for initiating Synaptic transmission and calcium influx induced by（-）clausenamide may promote the release of intracellular calcium responsible for synaptic enhancement.Conclusion（-）clausenamide promoted calcium influx to initiating Synaptic transmission and triggering intracellular calcium release,and subsequently activated CaMKIIα-ERK1/2 -CREB signal pathway.

关键词： (-)clausenamide Synaptic transmission CaMKIIα calcium

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Polygalasaponin ⅩⅩⅩⅡ improves hippocampal-dependent learning and memory through Synaptic transmission,the MAPK cascade and BDNF

Polygalasaponin ⅩⅩⅩⅡ improves hippocampal-dependent lear...

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中国药理学会第十次全国学术会议

作者： Wei Xue,Jin-Feng Hu,Yu-He Yuan,Jian-Dong Sun,Bo-Yu Li,Dong-Ming Zhang,Chuang-Jun Li,Nai-Hong Chen

Aim To investigate the cognition-enhancing activity and underlying mechanisms of a triterpenoid saponin (PolygalasaponinXXXII,PGS32) isolated from the roots of Polygala tenuifolia Willd.Methods Morris water maze was used to evaluate the spatial learning and memory of mice.Electrophysiological recording of evoked potential was applied to detect the basic Synaptic transmission and LTP(long-term potentiation) in the dentate gynus of rats.Western blotting analysis was used to determine the phosphorylation of ERK,CREB,SynapsinI and the ex- pression of BDNF.Results When supplied at 0.125,0.5,or 2 mg/kg,PGS32 could significantly prevent scopolamine -induced cognitive impairments in mice.Intracerebroventricular(i.c.v.) administration of PGS32 at 1μmol/L greatly enhanced basic Synaptic transmission in the dentate gynus of rats and induced LTP.In PC12 cells, as well as in the hippocampus of maze-trained mice,PGS32 was found to activate the MAP kinase cascade by promoting phosphorylation of ERK,CREB and Synapsinl.Expression of BDNF was also greatly enhanced in the hippocampus. Conclusion Our findings suggest that PGS32 can improve hippocampal-dependent learning and memory, possibly through improvement of Synaptic transmission,activation of the MAP kinase cascade and enhancement of the level of BDNF.PGS32 therefore shows promise as a potential cognition-enhancing therapeutic drug.

关键词： Polygala tenuifolia Willd triterpenoid saponin learning and memory Synaptic transmission MAP kinase signaling system BDNF

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Estrogen produced by astrocyte strengthens synaptogenesis and Synaptic transmission between cultured cortical neurons

Estrogen produced by astrocyte strengthens synaptogenesis an...

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中国神经科学学会第六届学术会议暨学会成立十周年庆祝大会

作者：胡荣蔡文琴第三军医大学神经生物学教研室第三军医大学神经生物学教研室

＜正＞Recent in vitro studies have found that astrocytes exert powerful control over the number of neuronal synapses , leading us to consider why glia can exert this control and what the underlying mechanism（s） may be. Neuroactive steroids such as estrogen can be synthesized in the brain where they have been shown to have functionanlly diverse roles in the nervous system and especially in regards to synaptic plasticity. Aromatase, a key enzyme, a key enzyme in the synthesis of estrogens expressed in glia. We therefore proposed that the astrocyte can influence synapse formation and Synaptic transmission through

关键词： estrogen synaptogenesis Synaptic transmission astrocyte

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Insulin Age-Dependently Modulates Synaptic transmission and AMPA Receptor Trafficking in Region CA1 of the Rat Hippocampus

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Open Journal of Molecular and Integrative Physiology 2016年第2期6卷 19-33页

作者： Shayna A. Wrighten Gerardo G. Piroli Department of Biology Francis Marion University Florence SC USA Department of Pharmacology Physiology and Neuroscience University of South Carolina School of Medicine Columbia SC USA

Insulin induces long-term depression (insulin-LTD) in the CA1 region of the rat juvenile hippocampus. This insulin-LTD may be due in part to internalization of the GluA2 subunit of the AMPA receptor (AMPAR) events that haven’t been studied in the mature rat hippocampus. In our studies, we used hippocampal preparations from juvenile (14 - 25 days) and mature (60 - 90 days) rats to assess insulin modulation of CA1 Synaptic transmission and AMPAR trafficking and phosphorylation. Using field potential electrophysiology, we observed that insulin induced LTD in the juvenile hippocampus (as previously reported) in the presence and absence of phosphoinositide 3-kinase (PI3K) activity, but produced no significant long-term changes in the mature hippocampus in the presence of PI3K activity. Interestingly, during PI3K inhibition, insulin did produce LTD in the mature hippocampus. Additionally, insulin induced a long-term decrease in plasma membrane expression of the GluA2 and GluA1 subunits of the AMPAR in the juvenile, but not mature hippocampus. Furthermore, there was a long-term decrease in GluA1 phosphorylation at Serine 845 in the juvenile, but not mature hippocampus. These data reveal that insulin modulation of synaptic plasticity and AMPAR modulation within the hippocampus is age-dependent, suggesting that insulin-regulated behaviors may also show age-dependence. These findings are important largely due to the increased use of insulin as a therapeutic throughout the lifespan. Our data suggest that additional work should be done to determine how this use of insulin throughout different stages of life might affect synaptic function and development.

关键词： Insulin synaptic Plasticity Synaptic transmission Long-Term Depression (LTD)

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