Frontiers in Synaptic Neuroscience最新文献

{"title":"Editorial: Molecular Nanomachines of the Presynaptic Terminal, Volume II.","authors":"Lucia Tabares, Silvio O Rizzoli","doi":"10.3389/fnsyn.2022.941339","DOIUrl":"https://doi.org/10.3389/fnsyn.2022.941339","url":null,"abstract":"","PeriodicalId":12650,"journal":{"name":"Frontiers in Synaptic Neuroscience","volume":null,"pages":null},"PeriodicalIF":3.7,"publicationDate":"2022-06-07","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC9211065/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"40391178","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":"SHANK3 Antibody Validation: Differential Performance in Western Blotting, Immunocyto- and Immunohistochemistry.","authors":"Anne-Kathrin Lutz,&nbsp;Helen Friedericke Bauer,&nbsp;Valentin Ioannidis,&nbsp;Michael Schön,&nbsp;Tobias M Boeckers","doi":"10.3389/fnsyn.2022.890231","DOIUrl":"https://doi.org/10.3389/fnsyn.2022.890231","url":null,"abstract":"<p><p>SHANK3 is a scaffolding protein implicated in autism spectrum disorders (ASD). Its function at excitatory glutamatergic synapses has been studied for the last two decades, however, tissue-specific expression patterns as well as its subcellular localization need to be studied in further detail. Especially the close sequence homology of SHANK3 to its protein family members SHANK2 and SHANK1 raises the emerging need for specific antibodies that are validated for the desired methodology. With this study, we aim to validate a set of commercial as well as homemade SHANK3 antibodies in Western Blotting, and synaptic immunocyto- and immunohistochemistry. We found that only a small subset of the antibodies included in this study meet the criteria of quality and specificity. Therefore, we aim to share our findings on SHANK3 antibody validation but also raise awareness of the necessity of antibody specificity testing in the field.</p>","PeriodicalId":12650,"journal":{"name":"Frontiers in Synaptic Neuroscience","volume":null,"pages":null},"PeriodicalIF":3.7,"publicationDate":"2022-06-06","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC9207774/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"40224765","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":"Enhanced Non-Associative Long-Term Potentiation in Immature Granule Cells in the Dentate Gyrus of Adult Rats","authors":"N. A. Simonova, M. Volgushev, A. Malyshev","doi":"10.3389/fnsyn.2022.889947","DOIUrl":"https://doi.org/10.3389/fnsyn.2022.889947","url":null,"abstract":"The dentate gyrus is one of the few sites of neurogenesis in the adult brain. Integration of new-generated granule cells into the hippocampal circuitry provides a substrate for structural plasticity, fundamental for normal function of adult hippocampus. However, mechanisms of synaptic plasticity that mediate integration of new-generated granule cells into the existing circuitry remain poorly understood. Especially mechanisms of plasticity at GABA-ergic synapses remain elusive. Here, we show that postsynaptic spiking without presynaptic activation can induce heterosynaptic, non-associative plasticity at GABA-ergic inputs to both immature and mature granule cells. In both immature and mature neurons, plastic changes were bidirectional and individual inputs could express long-term potentiation (LTP) or long-term depression (LTD), or do not change. However, properties of non-associative plasticity dramatically change with maturation of newly generated granule cells: while in immature cells there was a clear predominance of non-associative LTP and net potentiation across the inputs, in mature neurons, potentiation and depression were balanced with no net change on average. We conclude that GABA-ergic inputs to granule cells are plastic, and that the rules for induction of non-associative plasticity change with maturation. We propose that potentiation-biased non-associative plasticity of GABA-ergic transmission might help to counter-balance an increase of excitatory drive that is facilitated by enhanced LTP at glutamatergic synapses in maturating granule cells. Such mechanism might help to build a strong GABA-ergic input to surviving active new cells, necessary for normal function of mature granule cells, which operate under a tight inhibitory control and generate sparse spiking activity.","PeriodicalId":12650,"journal":{"name":"Frontiers in Synaptic Neuroscience","volume":null,"pages":null},"PeriodicalIF":3.7,"publicationDate":"2022-05-30","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"48194037","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":4,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"Ameliorative Potential of Hot Compress on Sciatic Nerve Pain in Chronic Constriction Injury-Induced Rat Model","authors":"K. Chan, W. Tsai, Chien-Yi Chiang, M. Sheu, Chih-Yang Huang, Yi-Ching Tsai, Chia-Yun Tsai, Chia-Jung Lu, Z-P Ho, D. Lai","doi":"10.3389/fnsyn.2022.859278","DOIUrl":"https://doi.org/10.3389/fnsyn.2022.859278","url":null,"abstract":"Hot compress modalities are used to ameliorate pain despite prevalent confusion about which modality should be used and when. Most recommendations for hot compresses are based on empirical experience, with limited evidence to support its efficacy. To obtain insight into the nerve transmission mechanism of hot compresses and to identify the nerve injury marker proteins specifically associated with sciatic nerve pain, we established a rat model of chronic constriction injury (CCI) and performed mechanical allodynia, electrophysiology, and histopathological analysis. All CCI rats exhibited geometric representation of the affected hind paw, which indicated a hyper-impact on both mechanical gait and asymmetry of gait on day 28. The CCI model after 28 days of surgery significantly reduced compound muscle action potential (CMAP) amplitude, but also significantly reduced latency. Administration of hot compress for 3 weeks (heated at 40–42°C, cycle of 40 min, and rest for 20 min, three cycles each time, three times per week) significantly increased the paw withdrawal thresholds in response to stimulation by Von Frey fibers and reversed the CCI-induced reduced sciatic functional index (SFI) scores. Hot compress treatment in the CCI model improved CMAP amplitude and latency. The S100 protein expression level in the CCI+Hot compression group was 1.5-fold higher than in the CCI group; it dramatically reduced inflammation, such as tumor necrosis factor alpha and CD68 expression in nerve injury sites. Synaptophysin (Syn) expression in the CCI+Hot compression group was less than threefold in the CCI group at both nerve injury sites and brain (somatosensory cortex and hippocampus). This finding indicates that local nerve damage and inflammation cause significant alterations in the sensorimotor strip, and hot compress treatment could significantly ameliorate sciatic nerve pain by attenuating Syn and inflammatory factors from local pathological nerves to the brain. This study determines the potential efficacy and safety of hot compress, and may have important implications for its widespread use in sciatic nerve pain treatment.","PeriodicalId":12650,"journal":{"name":"Frontiers in Synaptic Neuroscience","volume":null,"pages":null},"PeriodicalIF":3.7,"publicationDate":"2022-05-24","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"43155074","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":4,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"Correlative Assembly of Subsynaptic Nanoscale Organizations During Development.","authors":"Shi-Yan Sun, Xiao-Wei Li, Ran Cao, Yang Zhao, Nengyin Sheng, Ai-Hui Tang","doi":"10.3389/fnsyn.2022.748184","DOIUrl":"10.3389/fnsyn.2022.748184","url":null,"abstract":"<p><p>Nanoscale organization of presynaptic proteins determines the sites of transmitter release, and its alignment with assemblies of postsynaptic receptors through nanocolumns is suggested to optimize the efficiency of synaptic transmission. However, it remains unknown how these nano-organizations are formed during development. In this study, we used super-resolution stochastic optical reconstruction microscopy (STORM) imaging technique to systematically analyze the evolvement of subsynaptic organization of three key synaptic proteins, namely, RIM1/2, GluA1, and PSD-95, during synapse maturation in cultured hippocampal neurons. We found that volumes of synaptic clusters and their subsynaptic heterogeneity increase as synapses get matured. Synapse sizes of presynaptic and postsynaptic compartments correlated well at all stages, while only more mature synapses demonstrated a significant correlation between presynaptic and postsynaptic nano-organizations. After a long incubation with an inhibitor of action potentials or AMPA receptors, both presynaptic and postsynaptic compartments showed increased synaptic cluster volume and subsynaptic heterogeneity; however, the trans-synaptic alignment was intact. Together, our results characterize the evolvement of subsynaptic protein architectures during development and demonstrate that the nanocolumn is organized more likely by an intrinsic mechanism and independent of synaptic activities.</p>","PeriodicalId":12650,"journal":{"name":"Frontiers in Synaptic Neuroscience","volume":null,"pages":null},"PeriodicalIF":2.8,"publicationDate":"2022-05-24","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC9171000/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"42070690","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":"The Yin and Yang of GABAergic and Glutamatergic Synaptic Plasticity: Opposites in Balance by Crosstalking Mechanisms.","authors":"Caitlyn A Chapman, Jessica L Nuwer, Tija C Jacob","doi":"10.3389/fnsyn.2022.911020","DOIUrl":"10.3389/fnsyn.2022.911020","url":null,"abstract":"<p><p>Synaptic plasticity is a critical process that regulates neuronal activity by allowing neurons to adjust their synaptic strength in response to changes in activity. Despite the high proximity of excitatory glutamatergic and inhibitory GABAergic postsynaptic zones and their functional integration within dendritic regions, concurrent plasticity has historically been underassessed. Growing evidence for pathological disruptions in the excitation and inhibition (E/I) balance in neurological and neurodevelopmental disorders indicates the need for an improved, more \"holistic\" understanding of synaptic interplay. There continues to be a long-standing focus on the persistent strengthening of excitation (excitatory long-term potentiation; eLTP) and its role in learning and memory, although the importance of inhibitory long-term potentiation (iLTP) and depression (iLTD) has become increasingly apparent. Emerging evidence further points to a dynamic dialogue between excitatory and inhibitory synapses, but much remains to be understood regarding the mechanisms and extent of this exchange. In this mini-review, we explore the role calcium signaling and synaptic crosstalk play in regulating postsynaptic plasticity and neuronal excitability. We examine current knowledge on GABAergic and glutamatergic synapse responses to perturbances in activity, with a focus on postsynaptic plasticity induced by short-term pharmacological treatments which act to either enhance or reduce neuronal excitability via ionotropic receptor regulation in neuronal culture. To delve deeper into potential mechanisms of synaptic crosstalk, we discuss the influence of synaptic activity on key regulatory proteins, including kinases, phosphatases, and synaptic structural/scaffolding proteins. Finally, we briefly suggest avenues for future research to better understand the crosstalk between glutamatergic and GABAergic synapses.</p>","PeriodicalId":12650,"journal":{"name":"Frontiers in Synaptic Neuroscience","volume":null,"pages":null},"PeriodicalIF":3.7,"publicationDate":"2022-05-19","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC9160301/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"9073317","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":"Visualizing Presynaptic Active Zones and Synaptic Vesicles.","authors":"Manfred Heckmann, Martin Pauli","doi":"10.3389/fnsyn.2022.901341","DOIUrl":"10.3389/fnsyn.2022.901341","url":null,"abstract":"<p><p>The presynaptic active zone (AZ) of chemical synapses is a highly dynamic compartment where synaptic vesicle fusion and neurotransmitter release take place. During evolution the AZ was optimized for speed, accuracy, and reliability of chemical synaptic transmission in combination with miniaturization and plasticity. Single-molecule localization microscopy (SMLM) offers nanometer spatial resolution as well as information about copy number, localization, and orientation of proteins of interest in AZs. This type of imaging allows quantifications of activity dependent AZ reorganizations, e.g., in the context of presynaptic homeostatic potentiation. In combination with high-pressure freezing and optogenetic or electrical stimulation AZs can be imaged with millisecond temporal resolution during synaptic activity. Therefore SMLM allows the determination of key parameters in the complex spatial environment of AZs, necessary for next generation simulations of chemical synapses with realistic protein arrangements.</p>","PeriodicalId":12650,"journal":{"name":"Frontiers in Synaptic Neuroscience","volume":null,"pages":null},"PeriodicalIF":2.8,"publicationDate":"2022-05-18","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC9159495/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"42494721","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":"Chemical Imaging and Analysis of Single Nerve Cells by Secondary Ion Mass Spectrometry Imaging and Cellular Electrochemistry.","authors":"Alicia A Lork, Kim L L Vo, Nhu T N Phan","doi":"10.3389/fnsyn.2022.854957","DOIUrl":"10.3389/fnsyn.2022.854957","url":null,"abstract":"<p><p>A nerve cell is a unit of neuronal communication in the nervous system and is a heterogeneous molecular structure, which is highly mediated to accommodate cellular functions. Understanding the complex regulatory mechanisms of neural communication at the single cell level requires analytical techniques with high sensitivity, specificity, and spatial resolution. Challenging technologies for chemical imaging and analysis of nerve cells will be described in this review. Secondary ion mass spectrometry (SIMS) allows for non-targeted and targeted molecular imaging of nerve cells and synapses at subcellular resolution. Cellular electrochemistry is well-suited for quantifying the amount of reactive chemicals released from living nerve cells. These techniques will also be discussed regarding multimodal imaging approaches that have recently been shown to be advantageous for the understanding of structural and functional relationships in the nervous system. This review aims to provide an insight into the strengths, limitations, and potentials of these technologies for synaptic and neuronal analyses.</p>","PeriodicalId":12650,"journal":{"name":"Frontiers in Synaptic Neuroscience","volume":null,"pages":null},"PeriodicalIF":2.8,"publicationDate":"2022-05-16","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC9149580/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"41564452","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":"Dexmedetomidine and Ketamine Attenuated Neuropathic Pain Related Behaviors via STING Pathway to Induce ER-Phagy","authors":"Yongda Liu, Shihui Kuai, M. Ding, Zhibin Wang, Limei Zhao, P. Zhao","doi":"10.3389/fnsyn.2022.891803","DOIUrl":"https://doi.org/10.3389/fnsyn.2022.891803","url":null,"abstract":"Our previous work indicated that ER-phagy level had altered in spinal nerve ligation (SNL) rats. In this study, we investigated whether dexmedetomidine or ketamine exhibits anti-anxiety or anti-nociceptive effects via modulation of the spinal STING/TBK pathway to alter ER-phagy in SNL rats. We evaluated the analgesic and anti-anxiety effects of ketamine and dexmedetomidine in SNL rats. 2’3’-cGAMP (a STING pathway agonist) was administrated to investigate whether enhanced spinal STING pathway activation could inhibit dexmedetomidine or ketamine treatment effects in SNL rats. Analgesic effects were assessed with the mechanical withdrawal threshold (MWT) and anti-anxiety effects were measured via an open field test (OFT). Protein expression levels were evaluated by immunoblotting. Distribution and cellular localization of Grp78 (ER stress marker) were evaluated by confocal immunofluorescence. SNL induced mechanical hypersensitivity and anxiety in rats; dexmedetomidine and ketamine both provided analgesia and anti-anxiety effects in SNL rats. Furthermore, the STING pathway was involved in the modulation of ER stress and ER-phagy in SNL rats and dexmedetomidine and ketamine alleviated ER stress by inhibiting STING pathway to enhance ER-phagy. Thus, both ketamine and dexmedetomidine provided anti-anxiety and anti-nociceptive effects by alleviating ER stress through the inhibition of the STING/TBK pathway to modulate spinal ER-phagy in SNL rats.","PeriodicalId":12650,"journal":{"name":"Frontiers in Synaptic Neuroscience","volume":null,"pages":null},"PeriodicalIF":3.7,"publicationDate":"2022-05-13","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"48869886","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":4,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"Presynaptic Mitochondria Communicate With Release Sites for Spatio-Temporal Regulation of Exocytosis at the Motor Nerve Terminal","authors":"Mario López-Manzaneda, Andrea Fuentes-Moliz, L. Tabares","doi":"10.3389/fnsyn.2022.858340","DOIUrl":"https://doi.org/10.3389/fnsyn.2022.858340","url":null,"abstract":"Presynaptic Ca2+ regulation is critical for accurate neurotransmitter release, vesicle reloading of release sites, and plastic changes in response to electrical activity. One of the main players in the regulation of cytosolic Ca2+ in nerve terminals is mitochondria, which control the size and spread of the Ca2+ wave during sustained electrical activity. However, the role of mitochondria in Ca2+ signaling during high-frequency short bursts of action potentials (APs) is not well known. Here, we studied spatial and temporal relationships between mitochondrial Ca2+ (mCa2+) and exocytosis by live imaging and electrophysiology in adult motor nerve terminals of transgenic mice expressing synaptophysin-pHluorin (SypHy). Our results show that hot spots of exocytosis and mitochondria are organized in subsynaptic functional regions and that mitochondria start to uptake Ca2+ after a few APs. We also show that mitochondria contribute to the regulation of the mode of fusion (synchronous and asynchronous) and the kinetics of release and replenishment of the readily releasable pool (RRP) of vesicles. We propose that mitochondria modulate the timing and reliability of neurotransmission in motor nerve terminals during brief AP trains.","PeriodicalId":12650,"journal":{"name":"Frontiers in Synaptic Neuroscience","volume":null,"pages":null},"PeriodicalIF":3.7,"publicationDate":"2022-05-12","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"45027014","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":4,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}