Frontiers in Synaptic Neuroscience最新文献

{"title":"Editorial: NMDA receptors in physiology and disease.","authors":"María Verónica Baez, Julien P Dupuis, Gaston Diego Calfa","doi":"10.3389/fnsyn.2023.1163459","DOIUrl":"https://doi.org/10.3389/fnsyn.2023.1163459","url":null,"abstract":"COPYRIGHT © 2023 Baez, Dupuis and Calfa. This is an open-access article distributed under the terms of the Creative Commons Attribution License (CC BY). The use, distribution or reproduction in other forums is permitted, provided the original author(s) and the copyright owner(s) are credited and that the original publication in this journal is cited, in accordance with accepted academic practice. No use, distribution or reproduction is permitted which does not comply with these terms. Editorial: NMDA receptors in physiology and disease","PeriodicalId":12650,"journal":{"name":"Frontiers in Synaptic Neuroscience","volume":null,"pages":null},"PeriodicalIF":3.7,"publicationDate":"2023-01-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC10018128/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"9193741","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":4,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"OA","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"Recording plasticity in neuronal activity in the rodent intrinsic cardiac nervous system using calcium imaging techniques.","authors":"Joscelin E G Smith,&nbsp;Jesse L Ashton,&nbsp;Liam P Argent,&nbsp;Juliette E Cheyne,&nbsp;Johanna M Montgomery","doi":"10.3389/fnsyn.2023.1104736","DOIUrl":"https://doi.org/10.3389/fnsyn.2023.1104736","url":null,"abstract":"<p><p>The intrinsic cardiac nervous system (ICNS) is composed of interconnected clusters of neurons called ganglionated plexi (GP) which play a major role in controlling heart rate and rhythm. The function of these neurons is particularly important due to their involvement in cardiac arrhythmias such as atrial fibrillation (AF), and previous work has shown that plasticity in GP neural networks could underpin aberrant activity patterns that drive AF. As research in this field increases, developing new techniques to visualize the complex interactions and plasticity in this GP network is essential. In this study we have developed a calcium imaging method enabling the simultaneous recording of plasticity in neuronal activity from multiple neurons in intact atrial GP networks. Calcium imaging was performed with Cal-520 AM labeling in aged spontaneously hypertensive rats (SHRs), which display both spontaneous and induced AF, and age-matched Wistar Kyoto (WKY) controls to determine the relationship between chronic hypertension, arrhythmia and GP calcium dynamics. Our data show that SHR GPs have significantly larger calcium responses to cholinergic stimulation compared to WKY controls, as determined by both higher amplitude and longer duration calcium responses. Responses were significantly but not fully blocked by hexamethonium, indicating multiple cholinergic receptor subtypes are involved in the calcium response. Given that SHRs are susceptible to cardiac arrhythmias, our data provide evidence for a potential link between arrhythmia and plasticity in calcium dynamics that occur not only in cardiomyocytes but also in the GP neurons of the heart.</p>","PeriodicalId":12650,"journal":{"name":"Frontiers in Synaptic Neuroscience","volume":null,"pages":null},"PeriodicalIF":3.7,"publicationDate":"2023-01-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC10110955/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"9379235","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":4,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"OA","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"Cryo-EM tomography and automatic segmentation delineate modular structures in the postsynaptic density.","authors":"Jae Hoon Jung,&nbsp;Xiaobing Chen,&nbsp;Thomas S Reese","doi":"10.3389/fnsyn.2023.1123564","DOIUrl":"https://doi.org/10.3389/fnsyn.2023.1123564","url":null,"abstract":"<p><p>Postsynaptic densities (PSDs) are large protein complexes associated with the postsynaptic membrane of excitatory synapses important for synaptic function including plasticity. Conventional electron microscopy (EM) typically depicts PSDs as compact disk-like structures of hundreds of nanometers in size. Biochemically isolated PSDs were also similar in dimension revealing a predominance of proteins with the ability to polymerize into an extensive scaffold; several EM studies noted their irregular contours with often small granular structures (<30 nm) and holes. Super-resolution light microscopy studies observed clusters of PSD elements and their activity-induced lateral movement. Furthermore, our recent EM study on PSD fractions after sonication observed PSD fragments (40-90 nm in size) separate from intact PSDs; however, such structures within PSDs remained unidentified. Here we examined isolated PSDs by cryo-EM tomography with our new approach of automatic segmentation that enables delineation of substructures and their quantitative analysis. The delineated substructures broadly varied in size, falling behind 30 nm or exceeding 100 nm and showed that a considerable portion of the substructures (>38%) in isolated PSDs was in the same size range as those fragments. Furthermore, substructures spanning the entire thickness of the PSD were found, large enough to contain both membrane-associated and cytoplasmic proteins of the PSD; interestingly, they were similar to nanodomains in frequency. The structures detected here appear to constitute the isolated PSD as modules of various compositions, and this modular nature may facilitate remodeling of the PSD for proper synaptic function and plasticity.</p>","PeriodicalId":12650,"journal":{"name":"Frontiers in Synaptic Neuroscience","volume":null,"pages":null},"PeriodicalIF":3.7,"publicationDate":"2023-01-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC10117989/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"9742651","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":4,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"OA","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"Latest updates on the serotonergic system in depression and anxiety.","authors":"Jianwen Lin,&nbsp;Wenxin Liu,&nbsp;Jing Guan,&nbsp;Jianing Cui,&nbsp;Ruolin Shi,&nbsp;Lu Wang,&nbsp;Dong Chen,&nbsp;Yi Liu","doi":"10.3389/fnsyn.2023.1124112","DOIUrl":"https://doi.org/10.3389/fnsyn.2023.1124112","url":null,"abstract":"<p><p>Psychiatric disorders are among the leading causes of global health burden, with depression and anxiety being the most disabling subtypes. The two common disorders, depression and anxiety, usually coexist and are pathologically polygenic with complicated etiologies. Current drug-based therapies include selective serotonin reuptake inhibitors, serotonin and norepinephrine reuptake inhibitors, and 5-hydroxytryptamine partial agonists. However, these modalities share common limitations, such as slow onset and low efficacy, which is why potential mechanistic insights for new drug targets are needed. In this review, we summarize recent advances in brain localization, pathology, and therapeutic mechanisms of the serotonergic system in depression and anxiety.</p>","PeriodicalId":12650,"journal":{"name":"Frontiers in Synaptic Neuroscience","volume":null,"pages":null},"PeriodicalIF":3.7,"publicationDate":"2023-01-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC10203201/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"9896457","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":4,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"OA","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"Triose-phosphate isomerase deficiency is associated with a dysregulation of synaptic vesicle recycling in <i>Drosophila melanogaster</i>.","authors":"Aelfwin Stone,&nbsp;Oliver Cujic,&nbsp;Angel Rowlett,&nbsp;Sophia Aderhold,&nbsp;Emma Savage,&nbsp;Bruce Graham,&nbsp;Joern R Steinert","doi":"10.3389/fnsyn.2023.1124061","DOIUrl":"https://doi.org/10.3389/fnsyn.2023.1124061","url":null,"abstract":"<p><strong>Introduction: </strong>Numerous neurodegenerative diseases are associated with neuronal dysfunction caused by increased redox stress, often linked to aberrant production of redox-active molecules such as nitric oxide (NO) or oxygen free radicals. One such protein affected by redox-mediated changes is the glycolytic enzyme triose-phosphate isomerase (TPI), which has been shown to undergo 3-nitrotyrosination (a NO-mediated post-translational modification) rendering it inactive. The resulting neuronal changes caused by this modification are not well understood. However, associated glycation-induced cytotoxicity has been reported, thus potentially causing neuronal and synaptic dysfunction via compromising synaptic vesicle recycling.</p><p><strong>Methods: </strong>This work uses <i>Drosophila melanogaster</i> to identify the impacts of altered TPI activity on neuronal physiology, linking aberrant TPI function and redox stress to neuronal defects. We used <i>Drosophila</i> mutants expressing a missense allele of the TPI protein, M81T, identified in a previous screen and resulting in an inactive mutant of the TPI protein (<i>TPI^M81T</i> , wstd¹). We assessed synaptic physiology at the glutamatergic <i>Drosophila</i> neuromuscular junction (NMJ), synapse morphology and behavioural phenotypes, as well as impacts on longevity.</p><p><strong>Results: </strong>Electrophysiological recordings of evoked and spontaneous excitatory junctional currents, alongside high frequency train stimulations and recovery protocols, were applied to investigate synaptic depletion and subsequent recovery. Single synaptic currents were unaltered in the presence of the wstd¹ mutation, but frequencies of spontaneous events were reduced. Wstd¹ larvae also showed enhanced vesicle depletion rates at higher frequency stimulation, and subsequent recovery times for evoked synaptic responses were prolonged. A computational model showed that TPI mutant larvae exhibited a significant decline in activity-dependent vesicle recycling, which manifests itself as increased recovery times for the readily-releasable vesicle pool. Confocal images of NMJs showed no morphological or developmental differences between wild-type and wstd¹ but TPI mutants exhibited learning impairments as assessed by olfactory associative learning assays.</p><p><strong>Discussion: </strong>Our data suggests that the wstd¹ phenotype is partially due to altered vesicle dynamics, involving a reduced vesicle pool replenishment, and altered endo/exocytosis processes. This may result in learning and memory impairments and neuronal dysfunction potentially also presenting a contributing factor to other reported neuronal phenotypes.</p>","PeriodicalId":12650,"journal":{"name":"Frontiers in Synaptic Neuroscience","volume":null,"pages":null},"PeriodicalIF":3.7,"publicationDate":"2023-01-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC10011161/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"9131154","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":4,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"OA","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"GluN2B-NMDAR subunit contribution on synaptic plasticity: A phenomenological model for CA3-CA1 synapses.","authors":"Justinas J Dainauskas,&nbsp;Hélène Marie,&nbsp;Michele Migliore,&nbsp;Ausra Saudargiene","doi":"10.3389/fnsyn.2023.1113957","DOIUrl":"https://doi.org/10.3389/fnsyn.2023.1113957","url":null,"abstract":"<p><p>Synaptic plasticity is believed to be a key mechanism underlying learning and memory. We developed a phenomenological N-methyl-D-aspartate (NMDA) receptor-based voltage-dependent synaptic plasticity model for synaptic modifications at hippocampal CA3-CA1 synapses on a hippocampal CA1 pyramidal neuron. The model incorporates the GluN2A-NMDA and GluN2B-NMDA receptor subunit-based functions and accounts for the synaptic strength dependence on the postsynaptic NMDA receptor composition and functioning without explicitly modeling the NMDA receptor-mediated intracellular calcium, a local trigger of synaptic plasticity. We embedded the model into a two-compartmental model of a hippocampal CA1 pyramidal cell and validated it against experimental data of spike-timing-dependent synaptic plasticity (STDP), high and low-frequency stimulation. The developed model predicts altered learning rules in synapses formed on the apical dendrites of the detailed compartmental model of CA1 pyramidal neuron in the presence of the GluN2B-NMDA receptor hypofunction and can be used in hippocampal networks to model learning in health and disease.</p>","PeriodicalId":12650,"journal":{"name":"Frontiers in Synaptic Neuroscience","volume":null,"pages":null},"PeriodicalIF":3.7,"publicationDate":"2023-01-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC10050887/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"9296614","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":4,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"OA","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"Editorial: Synaptic plasticity and dysfunction, friend or foe?","authors":"Fereshteh S Nugent,&nbsp;Ka Wan Li,&nbsp;Lu Chen","doi":"10.3389/fnsyn.2023.1204605","DOIUrl":"https://doi.org/10.3389/fnsyn.2023.1204605","url":null,"abstract":"COPYRIGHT © 2023 Nugent, Li and Chen. This is an open-access article distributed under the terms of the Creative Commons Attribution License (CC BY). The use, distribution or reproduction in other forums is permitted, provided the original author(s) and the copyright owner(s) are credited and that the original publication in this journal is cited, in accordance with accepted academic practice. No use, distribution or reproduction is permitted which does not comply with these terms. Editorial: Synaptic plasticity and dysfunction, friend or foe?","PeriodicalId":12650,"journal":{"name":"Frontiers in Synaptic Neuroscience","volume":null,"pages":null},"PeriodicalIF":3.7,"publicationDate":"2023-01-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC10189113/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"9497004","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":4,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"OA","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"Editorial: Structural and quantitative modeling of synapses.","authors":"Jae Hoon Jung,&nbsp;Noreen E Reist,&nbsp;Sebastian Doniach","doi":"10.3389/fnsyn.2023.1254416","DOIUrl":"https://doi.org/10.3389/fnsyn.2023.1254416","url":null,"abstract":"COPYRIGHT © 2023 Jung, Reist and Doniach. This is an open-access article distributed under the terms of the Creative Commons Attribution License (CC BY). The use, distribution or reproduction in other forums is permitted, provided the original author(s) and the copyright owner(s) are credited and that the original publication in this journal is cited, in accordance with accepted academic practice. No use, distribution or reproduction is permitted which does not comply with these terms. Editorial: Structural and quantitative modeling of synapses","PeriodicalId":12650,"journal":{"name":"Frontiers in Synaptic Neuroscience","volume":null,"pages":null},"PeriodicalIF":3.7,"publicationDate":"2023-01-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC10407804/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"9966927","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":4,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"OA","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"Editorial: Signaling mechanisms of synapse assembly.","authors":"Zhihui Liu,&nbsp;Richard Sando,&nbsp;Bo Zhang,&nbsp;Xiaofei Yang","doi":"10.3389/fnsyn.2023.1154806","DOIUrl":"https://doi.org/10.3389/fnsyn.2023.1154806","url":null,"abstract":"COPYRIGHT © 2023 Liu, Sando, Zhang and Yang. This is an open-access article distributed under the terms of the Creative Commons Attribution License (CC BY). The use, distribution or reproduction in other forums is permitted, provided the original author(s) and the copyright owner(s) are credited and that the original publication in this journal is cited, in accordance with accepted academic practice. No use, distribution or reproduction is permitted which does not comply with these terms. Editorial: Signaling mechanisms of synapse assembly","PeriodicalId":12650,"journal":{"name":"Frontiers in Synaptic Neuroscience","volume":null,"pages":null},"PeriodicalIF":3.7,"publicationDate":"2023-01-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC9975732/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"10828607","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":4,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"OA","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"Synaptic alterations and neuronal firing in human epileptic neocortical excitatory networks.","authors":"Réka Bod,&nbsp;Kinga Tóth,&nbsp;Nour Essam,&nbsp;Estilla Zsófia Tóth,&nbsp;Loránd Erõss,&nbsp;László Entz,&nbsp;Attila G Bagó,&nbsp;Dániel Fabó,&nbsp;István Ulbert,&nbsp;Lucia Wittner","doi":"10.3389/fnsyn.2023.1233569","DOIUrl":"https://doi.org/10.3389/fnsyn.2023.1233569","url":null,"abstract":"<p><p>Epilepsy is a prevalent neurological condition, with underlying neuronal mechanisms involving hyperexcitability and hypersynchrony. Imbalance between excitatory and inhibitory circuits, as well as histological reorganization are relatively well-documented in animal models or even in the human hippocampus, but less is known about human neocortical epileptic activity. Our knowledge about changes in the excitatory signaling is especially scarce, compared to that about the inhibitory cell population. This study investigated the firing properties of single neurons in the human neocortex <i>in vitro</i>, during pharmacological blockade of glutamate receptors, and additionally evaluated anatomical changes in the excitatory circuit in tissue samples from epileptic and non-epileptic patients. Both epileptic and non-epileptic tissues exhibited spontaneous population activity (SPA), NMDA receptor antagonization reduced SPA recurrence only in epileptic tissue, whereas further blockade of AMPA/kainate receptors reversibly abolished SPA emergence regardless of epilepsy. Firing rates did not significantly change in excitatory principal cells and inhibitory interneurons during pharmacological experiments. Granular layer (L4) neurons showed an increased firing rate in epileptic compared to non-epileptic tissue. The burstiness of neurons remained unchanged, except for that of inhibitory cells in epileptic recordings, which decreased during blockade of glutamate receptors. Crosscorrelograms computed from single neuron discharge revealed both mono- and polysynaptic connections, particularly involving intrinsically bursting principal cells. Histological investigations found similar densities of SMI-32-immunopositive long-range projecting pyramidal cells in both groups, and shorter excitatory synaptic active zones with a higher proportion of perforated synapses in the epileptic group. These findings provide insights into epileptic modifications from the perspective of the excitatory system and highlight discrete alterations in firing patterns and synaptic structure. Our data suggest that NMDA-dependent glutamatergic signaling, as well as the excitatory synaptic machinery are perturbed in epilepsy, which might contribute to epileptic activity in the human neocortex.</p>","PeriodicalId":12650,"journal":{"name":"Frontiers in Synaptic Neuroscience","volume":null,"pages":null},"PeriodicalIF":3.7,"publicationDate":"2023-01-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC10450510/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"10105808","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":4,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"OA","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}