Frontiers in Synaptic Neuroscience最新文献

{"title":"Alzheimer's disease as a synaptopathy: Evidence for dysfunction of synapses during disease progression.","authors":"Soraya Meftah, Jian Gan","doi":"10.3389/fnsyn.2023.1129036","DOIUrl":"10.3389/fnsyn.2023.1129036","url":null,"abstract":"<p><p>The synapse has consistently been considered a vulnerable and critical target within Alzheimer's disease, and synapse loss is, to date, one of the main biological correlates of cognitive decline within Alzheimer's disease. This occurs prior to neuronal loss with ample evidence that synaptic dysfunction precedes this, in support of the idea that synaptic failure is a crucial stage within disease pathogenesis. The two main pathological hallmarks of Alzheimer's disease, abnormal aggregates of amyloid or tau proteins, have had demonstrable effects on synaptic physiology in animal and cellular models of Alzheimer's disease. There is also growing evidence that these two proteins may have a synergistic effect on neurophysiological dysfunction. Here, we review some of the main findings of synaptic alterations in Alzheimer's disease, and what we know from Alzheimer's disease animal and cellular models. First, we briefly summarize some of the human evidence to suggest that synapses are altered, including how this relates to network activity. Subsequently, animal and cellular models of Alzheimer's disease are considered, highlighting mouse models of amyloid and tau pathology and the role these proteins may play in synaptic dysfunction, either in isolation or examining how the two pathologies may interact in dysfunction. This specifically focuses on neurophysiological function and dysfunction observed within these animal models, typically measured using electrophysiology or calcium imaging. Following synaptic dysfunction and loss, it would be impossible to imagine that this would not alter oscillatory activity within the brain. Therefore, this review also discusses how this may underpin some of the aberrant oscillatory patterns seen in animal models of Alzheimer's disease and human patients. Finally, an overview of some key directions and considerations in the field of synaptic dysfunction in Alzheimer's disease is covered. This includes current therapeutics that are targeted specifically at synaptic dysfunction, but also methods that modulate activity to rescue aberrant oscillatory patterns. Other important future avenues of note in this field include the role of non-neuronal cell types such as astrocytes and microglia, and mechanisms of dysfunction independent of amyloid and tau in Alzheimer's disease. The synapse will certainly continue to be an important target within Alzheimer's disease for the foreseeable future.</p>","PeriodicalId":12650,"journal":{"name":"Frontiers in Synaptic Neuroscience","volume":"15 ","pages":"1129036"},"PeriodicalIF":2.8,"publicationDate":"2023-03-09","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC10033629/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"9561114","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":"mGluR-dependent plasticity in rodent models of Alzheimer's disease.","authors":"Gonzalo Valdivia, Alvaro O Ardiles, Abimbola Idowu, Claudia Salazar, Hey-Kyoung Lee, Michela Gallagher, Adrian G Palacios, Alfredo Kirkwood","doi":"10.3389/fnsyn.2023.1123294","DOIUrl":"10.3389/fnsyn.2023.1123294","url":null,"abstract":"<p><p>Long-term potentiation (LTP) and depression (LTD) are currently the most comprehensive models of synaptic plasticity models to subserve learning and memory. In the CA1 region of the hippocampus LTP and LTD can be induced by the activation of either NMDA receptors or mGluR5 metabotropic glutamate receptors. Alterations in either form of synaptic plasticity, NMDAR-dependent or mGluR-dependent, are attractive candidates to contribute to learning deficits in conditions like Alzheimer's disease (AD) and aging. Research, however, has focused predominantly on NMDAR-dependent forms of LTP and LTD. Here we studied age-associated changes in mGluR-dependent LTP and LTD in the APP/PS1 mouse model of AD and in <i>Octodon degu</i>, a rodent model of aging that exhibits features of AD. At 2 months of age, APP/PS1 mouse exhibited robust mGluR-dependent LTP and LTD that was completely lost by the 8th month of age. The expression of mGluR protein in the hippocampus of APP/PS1 mice was not affected, consistent with previous findings indicating the uncoupling of the plasticity cascade from mGluR5 activation. In <i>O. degu</i>, the average mGluR-LTD magnitude is reduced by half by the 3 <i>^rd</i> year of age. In aged <i>O. degu</i> individuals, the reduced mGluR-LTD correlated with reduced performance in a radial arm maze task. Altogether these findings support the idea that the preservation of mGluR-dependent synaptic plasticity is essential for the preservation of learning capacity during aging.</p>","PeriodicalId":12650,"journal":{"name":"Frontiers in Synaptic Neuroscience","volume":"15 ","pages":"1123294"},"PeriodicalIF":3.7,"publicationDate":"2023-03-02","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC10017879/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"10139412","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":"Calcium signaling in astrocytes and gliotransmitter release.","authors":"Julianna Goenaga, Alfonso Araque, Paulo Kofuji, Daniela Herrera Moro Chao","doi":"10.3389/fnsyn.2023.1138577","DOIUrl":"10.3389/fnsyn.2023.1138577","url":null,"abstract":"<p><p>Glia are as numerous in the brain as neurons and widely known to serve supportive roles such as structural scaffolding, extracellular ionic and neurotransmitter homeostasis, and metabolic support. However, over the past two decades, several lines of evidence indicate that astrocytes, which are a type of glia, play active roles in neural information processing. Astrocytes, although not electrically active, can exhibit a form of excitability by dynamic changes in intracellular calcium levels. They sense synaptic activity and release neuroactive substances, named gliotransmitters, that modulate neuronal activity and synaptic transmission in several brain areas, thus impacting animal behavior. This \"dialogue\" between astrocytes and neurons is embodied in the concept of the tripartite synapse that includes astrocytes as integral elements of synaptic function. Here, we review the recent work and discuss how astrocytes <i>via</i> calcium-mediated excitability modulate synaptic information processing at various spatial and time scales.</p>","PeriodicalId":12650,"journal":{"name":"Frontiers in Synaptic Neuroscience","volume":"15 ","pages":"1138577"},"PeriodicalIF":2.8,"publicationDate":"2023-03-02","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC10017551/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"9518873","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":"Memory retrieval, reconsolidation, and extinction: Exploring the boundary conditions of post-conditioning cue exposure.","authors":"Nicole C Ferrara, Janine L Kwapis, Sydney Trask","doi":"10.3389/fnsyn.2023.1146665","DOIUrl":"10.3389/fnsyn.2023.1146665","url":null,"abstract":"<p><p>Following fear conditioning, behavior can be reduced by giving many CS-alone presentations in a process known as extinction or by presenting a few CS-alone presentations and interfering with subsequent memory reconsolidation. While the two share procedural similarities, both the behavioral outcomes and the neurobiological underpinnings are distinct. Here we review the neural and behavioral mechanisms that produce these separate behavioral reductions, as well as some factors that determine whether or not a retrieval-dependent reconsolidation process or an extinction process will be in effect.</p>","PeriodicalId":12650,"journal":{"name":"Frontiers in Synaptic Neuroscience","volume":"15 ","pages":"1146665"},"PeriodicalIF":2.8,"publicationDate":"2023-03-02","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC10017482/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"9152967","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":"Exercise reduces the anxiogenic effects of meta-chlorophenylpiperazine: The role of 5-HT2C receptors in the bed nucleus of the stria terminalis.","authors":"James H Fox, Melissa N Boucher, Khalil S Abedrabbo, Brendan D Hare, Bethany A Grimmig, William A Falls, Sayamwong E Hammack","doi":"10.3389/fnsyn.2022.1067420","DOIUrl":"10.3389/fnsyn.2022.1067420","url":null,"abstract":"<p><strong>Introduction: </strong>Two weeks of voluntary exercise in group-housed mice produces a reduction in anxiety-like behaviors across a number of different measures, including a reduction in the anxiety levels typically produced by the anxiogenic serotonergic drug m-chlorophenylpiperazine (mCPP), an agonist at 5-HT2C/2b receptors. We have previously demonstrated that 2-weeks of voluntary exercise blunted the anxiogenic effects of systemic mCPP, and we have also shown that mCPP infused into the bed nucleus of the stria terminalis (BNST) is anxiogenic. Here we follow up on these reports.</p><p><strong>Methods: </strong>In Experiment 1 we infused several doses of mCPP into the BNST with or without the 5-HT2C antagonist SB242084. In Experiment 2, we administered mCPP into amygdala subregions and the dorsal hippocampus to investigate site specificity. In Experiment 4 we lesioned the BNST and subsequently infused mCPP systemically, and in Experiment 4 we used RNAscope^® to assess BNST 5-HT2C transcripts following wheel running.</p><p><strong>Results: </strong>BNST mCPP infusion increased acoustic startle responding, which was by 5-HT2C antagonism, while neither mCPP infused into the amygdala nor hippocampus was anxiogenic. Lesions of the BNST prevented the anxiogenic effect of systemically administered mCPP. Lastly, exercise reduced 5-HT2C transcripts in the BNST.</p><p><strong>Discussion: </strong>These results suggest that the BNST is a critical site of action for the effects of exercise on mCPP. Together these data suggest that exercise may reduce 5-HT2C receptor function in the BNST, which may, in part, explain some of the anxiolytic effects associated with wheel running.</p>","PeriodicalId":12650,"journal":{"name":"Frontiers in Synaptic Neuroscience","volume":"14 ","pages":"1067420"},"PeriodicalIF":2.8,"publicationDate":"2023-01-13","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC9880271/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"10585441","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":"Analytical approaches to examine gamma-aminobutyric acid and glutamate vesicular co-packaging.","authors":"SeulAh Kim, Bernardo L Sabatini","doi":"10.3389/fnsyn.2022.1076616","DOIUrl":"10.3389/fnsyn.2022.1076616","url":null,"abstract":"<p><p>Multi-transmitter neurons, i.e., those that release more than one type of neurotransmitter, have been found in many organisms and brain areas. Given the peculiar biology of these cells, as well as the potential for diverse effects of each of the transmitters released, new tools, and approaches are necessary to parse the mechanisms and functions of synaptic co-transmission. Recently, we and others have studied neurons that project to the lateral habenula and release both gamma-aminobutyric acid (GABA) and glutamate, in some cases by packaging both transmitters in the same synaptic vesicles. Here, we discuss the main challenges with current electrophysiological approaches to studying the mechanisms of glutamate/GABA co-release, a novel statistical analysis that can identify co-packaging of neurotransmitters versus release from separate vesicle, and the implications of glutamate/GABA co-release for synapse function and plasticity.</p>","PeriodicalId":12650,"journal":{"name":"Frontiers in Synaptic Neuroscience","volume":"14 ","pages":"1076616"},"PeriodicalIF":2.8,"publicationDate":"2023-01-04","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC9846491/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"9507353","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":"15 ","pages":"1124112"},"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":"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":"15 ","pages":"1123564"},"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":"Editorial: NMDA receptors in physiology and disease.","authors":"María Verónica Baez,&nbsp;Julien P Dupuis,&nbsp;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":"15 ","pages":"1163459"},"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":"15 ","pages":"1104736"},"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}