Frontiers in Synaptic Neuroscience最新文献

{"title":"Correction: Is it possible to prevent excessive synaptic pruning in schizophrenia? Possibilities and limitations.","authors":"Agnieszka Pawlak, Jakub Stefanowicz, Zofia Kotkowska, Agata Gabryelska, Marcin Sochal, Filip Napieraj, Magdalena Kotlicka-Antczak, Dominik Strzelecki","doi":"10.3389/fnsyn.2026.2007021","DOIUrl":"https://doi.org/10.3389/fnsyn.2026.2007021","url":null,"abstract":"<p><p>[This corrects the article DOI: 10.3389/fnsyn.2025.1656232.].</p>","PeriodicalId":12650,"journal":{"name":"Frontiers in Synaptic Neuroscience","volume":"18 ","pages":"2007021"},"PeriodicalIF":6.9,"publicationDate":"2026-09-30","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC13662645/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"149192753","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":"Time-resolved phenotyping of seizure evolution in developmental and epileptic encephalopathy: insights and gaps from the CYFIP2 Arg87Cys mouse model.","authors":"Ruiying Ma, U Suk Kim, Yousun Chung, Kihoon Han","doi":"10.3389/fnsyn.2026.1963161","DOIUrl":"10.3389/fnsyn.2026.1963161","url":null,"abstract":"<p><p>In developmental and epileptic encephalopathies (DEEs), the seizure phenotype is rarely static. Infantile epileptic spasms typically subside and are often replaced years later by other seizure types, and in several genetically defined DEEs seizure-free intervals precede seizure recurrence. Although these transitions are linked to long-term outcome, little is known about the molecular and cellular events that accompany them, because the interval is clinically silent and brain tissue is inaccessible. Animal studies have only partly filled this gap: most DEE models have been characterized at a single age, and models with continuous seizures provide no interval to investigate. We recently performed time-resolved deep phenotyping of <i>Cyfip2^+/R87C</i> mice, which recapitulate neonatal seizure-like events, a prolonged seizure-free interval, and adult-onset spontaneous recurrent seizures with premature death, using transcriptomic, ultrastructural, proteomic, and lipidomic analyses across four postnatal stages. Here we summarize the temporal landscape: excitatory synapse number falls while remaining synapses relocate to dendritic shafts, oligodendrocyte-lineage cells, microglia, and astrocytes are engaged sequentially, and lipid droplets accumulate progressively in astrocytes. We also highlight what remains unresolved. The highest-resolution analyses were performed only after seizure recurrence, illustrating a tradeoff between analytical depth and temporal coverage, so the juvenile interval preceding recurrence remains the central knowledge gap. Even so, the emerging picture is that the seizure-free interval is not a period of quiescence but one of active neuron-glia and metabolic remodeling. Defining this interval more precisely, and identifying biomarkers for patient staging, may transform a clinically silent phase into a well-defined therapeutic window for stage-specific intervention.</p>","PeriodicalId":12650,"journal":{"name":"Frontiers in Synaptic Neuroscience","volume":"18 ","pages":"1963161"},"PeriodicalIF":6.9,"publicationDate":"2026-09-24","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC13646908/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"149136208","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":"DHA-dominant Omega-3 compositions enhance PSD-95 organization and glutamatergic protein expression.","authors":"Gerardo Medina, Stephen D Baird, Lilia A Rodriguez-Alcocer, Alex E MacKenzie","doi":"10.3389/fnsyn.2026.1947075","DOIUrl":"10.3389/fnsyn.2026.1947075","url":null,"abstract":"<p><strong>Introduction: </strong>Docosahexaenoic acid (DHA), the predominant omega-3 (ω-3) fatty acid in the brain, which contributes to synaptic membrane organization and plasticity, is commonly recommended for brain health. However, ω-3 formulations commonly combine DHA with eicosapentaenoic acid (EPA) in varying proportions, and the impact of the DHA ratio on postsynaptic scaffold regulation remains unclear.</p><p><strong>Methods: </strong>In this study, differentiated human SH-SY5Y neurons were cultured in the presence of DHA, EPA, or defined DHA ratios (2:1, 1:1, 1:2) at equivalent total concentrations. PSD-95 expression, puncta density, colocalization with the presynaptic marker synaptophysin (SYN), and glutamatergic signaling proteins were quantified by immunofluorescence and Western blot analysis. Metabolic activity was assessed using a colorimetric MTT assay.</p><p><strong>Results: </strong>DHA produced the largest increase in PSD-95 protein abundance by immunoblot and the strongest effects on PSD-95 puncta density and SYN colocalization, accompanied by coordinated upregulation of N-methyl-D-aspartate receptor (NMDAR), α-amino-3-hydroxy-5-methyl-4-isoxazolepropionic acid receptor (AMPAR), and calcium/calmodulin-dependent protein kinase II (CaMKII). DHA-enriched compositions preserved this profile, whereas balanced or EPA-dominant compositions showed attenuated responses relative to DHA-dominant conditions. EPA alone failed to enhance postsynaptic scaffold abundance and reduced NMDAR levels relative to control. These effects occurred without a detectable reduction in cellular metabolic activity.</p><p><strong>Discussion: </strong>Collectively, these findings demonstrate that the composition of ω-3 fatty acid has a significant bearing on postsynaptic scaffold organization and glutamatergic signaling in differentiated neurons, with DHA serving as the chief mediator of observed effects. This composition-dependent framework provides an experimental basis for considering DHA ratio when evaluating omega-3 effects on postsynaptic protein organization.</p>","PeriodicalId":12650,"journal":{"name":"Frontiers in Synaptic Neuroscience","volume":"18 ","pages":"1947075"},"PeriodicalIF":6.9,"publicationDate":"2026-09-22","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC13638559/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"149108347","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: The diversity of the plasticitome.","authors":"Christina You Chien Chou, Serena M Dudek, Clive R Bramham, Hyungju Park, P Jesper Sjöström","doi":"10.3389/fnsyn.2026.1969861","DOIUrl":"10.3389/fnsyn.2026.1969861","url":null,"abstract":"","PeriodicalId":12650,"journal":{"name":"Frontiers in Synaptic Neuroscience","volume":"18 ","pages":"1969861"},"PeriodicalIF":6.9,"publicationDate":"2026-09-10","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC13601030/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"149038157","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":"Sleep disturbances as an early indicator of psychotic disorders in adolescents and young adults.","authors":"Julia Jaromirska, Dominik Strzelecki, Magdalena Kotlicka-Antczak, Piotr Białasiewicz, Agata Gabryelska","doi":"10.3389/fnsyn.2026.1949833","DOIUrl":"10.3389/fnsyn.2026.1949833","url":null,"abstract":"<p><p>Sleep disturbances are increasingly recognized as clinically relevant markers in the early detection of psychotic disorders among adolescents and young adults. These disturbances, including insomnia, circadian rhythm disruptions, parasomnias, and fragmented sleep, affect up to 70% of individuals at clinical high risk for psychosis, rising to 80% in fully developed schizophrenia. This review synthesizes current evidence on the relationship between sleep problems and early psychotic symptoms, emphasizing their potential as observable and possibly modifiable indicators of illness onset. Neurobiological mechanisms suggest overlapping pathways for both sleep problems and the development of psychotic symptoms involving dopaminergic, serotonergic, and hormonal dysregulation, which are additionally exacerbated by psychological factors such as stress, substance use, and poor sleep hygiene. Screening methods, such as self-report questionnaires, actigraphy, and polysomnography, have demonstrated utility in identifying individuals at risk. Furthermore, sleep-focused interventions, particularly cognitive behavioral therapy, show promise in alleviating both sleep and psychiatric symptoms. Despite methodological limitations of available research, including heterogeneous study designs and short follow-ups, sleep assessment can represent a low-cost, scalable tool for early intervention. Future research should prioritize longitudinal, multimodal studies and explore personalized, sleep-centered preventive strategies. Furthermore, sleep disorders could be considered not only as early signs of developing psychosis but also as a potential therapeutic target in psychosis prevention.</p>","PeriodicalId":12650,"journal":{"name":"Frontiers in Synaptic Neuroscience","volume":"18 ","pages":"1949833"},"PeriodicalIF":6.9,"publicationDate":"2026-09-04","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC13586941/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"149008309","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":"Activation of silent synapses driven by emerging technologies: mechanisms, disease associations, and prospects for clinical translation.","authors":"Yongli Li, Yong Liao, Shouyao Zhang, Chenggui Xu, Ruhua Lan, Pengbin Zhao, Ruilu Liu, Yongli Song, Xinghe Zhang","doi":"10.3389/fnsyn.2026.1923815","DOIUrl":"10.3389/fnsyn.2026.1923815","url":null,"abstract":"<p><p>Silent synapses represent a unique class of synaptic connections that are non-functional at rest but possess the potential to become functional, serving as a critical reservoir for neural plasticity. Their activation mechanisms not only challenge traditional models of synaptic maturation but also provide novel insights into brain function regulation and disease pathology. This article provides a systematic review of the regulatory mechanisms underlying silent synapse activation, encompassing pre-synaptic calcium signaling-mediated vesicle cycling and active zone (AZ) optimization, post-synaptic <i>α</i>-amino-3-hydroxy-5-methyl-4-isoxazolepropionic acid receptor (AMPAR) membrane insertion and post-synaptic density protein 95 (PSD-95) anchoring, Mg²⁺ blockade release by N-methyl-D-aspartate receptor (NMDAR), as well as synergistic integration of upstream signaling pathways. Additionally, it explores the roles of astrocytes, epigenetic modifications, ubiquitin-proteasome systems, and autophagy-lysosomal systems in multi-level regulatory processes. Notably, abnormal regulation of silent synapses exhibits two contrasting pathological patterns in diseases: \"desilencing impairment\" (e.g., Alzheimer's disease, depression) and \"abnormally excessive desilencing\" (e.g., drug addiction, chronic pain), which establishes a theoretical framework for targeted interventions. The study further evaluates the applicability and limitations of emerging technologies-including high-resolution imaging, single-cell omics, optogenetics, and AI-driven brain-inspired computing-in silent synapse research, while systematically summarizing clinical advancements, current challenges, and future directions, aiming to inform both fundamental neuroscience studies and therapeutic interventions.</p>","PeriodicalId":12650,"journal":{"name":"Frontiers in Synaptic Neuroscience","volume":"18 ","pages":"1923815"},"PeriodicalIF":6.9,"publicationDate":"2026-09-03","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC13581764/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"148989413","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":"Zebrafish as a translational model for peptide-mediated synaptic dysfunction related to obesity.","authors":"Amanda Costa Rodrigues, Adriel Parahyba Lacerda, Lincoln Takashi Hota Mukoyama, Gleyce Barrios de Carvalho, Júlia Aparecida Lima da Mata, Danieli Fernanda Buccini, Octavio Luiz Franco, Ludovico Migliolo","doi":"10.3389/fnsyn.2026.1845252","DOIUrl":"10.3389/fnsyn.2026.1845252","url":null,"abstract":"<p><p>Obesity-driven synaptic dysfunction is increasingly recognized as a key mechanism linking metabolic disorders to neurodegenerative diseases. This review aims to explore the utility of zebrafish (<i>Danio rerio</i>) as a translational model to investigate these mechanisms and screen peptide-based therapeutic strategies. Owing to their optical transparency, genetic tractability, and suitability for high-throughput screening, zebrafish provide a powerful platform for studying neuronal circuitry and evaluating bioactive peptides <i>in vivo</i>. Current evidence on pathophysiological processes underlying obesity-related synaptic impairment, including central resistance to metabolic hormones, oxidative stress, and the chronic inflammatory state, which promotes persistent immune activation and neuroinflammation. In addition, the persistence of these disturbances in the organism can lead to dysfunctions and pathologies, such as Parkinson's and Alzheimer's diseases, both of which are discussed in more detail in this review. Also, particular emphasis is placed on the roles of glial cells and the gut-brain axis in modulating synaptic integrity. We highlight how cutting-edge technologies, such as live neural imaging and single-cell transcriptomics, are accelerating peptide discovery and mechanism-of-action studies in zebrafish. Furthermore, we discuss emerging therapeutic peptides such as GLP-1 analogs and BDNF-based molecules that modulate inflammatory pathways, restore insulin signaling, and enhance neuronal resilience. Collectively, the evidence positions zebrafish as a robust model not only for elucidating disease mechanisms but also for advancing peptide-based interventions targeting synaptic dysfunction in obesity.</p>","PeriodicalId":12650,"journal":{"name":"Frontiers in Synaptic Neuroscience","volume":"18 ","pages":"1845252"},"PeriodicalIF":6.9,"publicationDate":"2026-08-10","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC13500655/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"148812915","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: Grey matters in the lab: utilizing human brain tissue for basic research, disease modeling and drug development.","authors":"Viktor Szegedi, Danqing Yang, Dirk Feldmeyer, Karri Lamsa","doi":"10.3389/fnsyn.2026.1910520","DOIUrl":"https://doi.org/10.3389/fnsyn.2026.1910520","url":null,"abstract":"","PeriodicalId":12650,"journal":{"name":"Frontiers in Synaptic Neuroscience","volume":"18 ","pages":"1910520"},"PeriodicalIF":6.9,"publicationDate":"2026-07-31","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC13474397/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"148764529","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":"Heterosynaptic NMDA receptor plasticity in hippocampal dentate granule cells.","authors":"Kaoutsar Nasrallah, Maryann Castillo, Stefano Lutzu, Pablo E Castillo, Alma Rodenas-Ruano","doi":"10.3389/fnsyn.2026.1825949","DOIUrl":"10.3389/fnsyn.2026.1825949","url":null,"abstract":"<p><p>The dentate gyrus is a key relay station that controls information transfer from the entorhinal cortex to the hippocampus proper. This process relies heavily on dendritic integration by dentate granule cells (GCs) of excitatory synaptic inputs from the medial and lateral entorhinal cortex via medial and lateral perforant paths (MPP and LPP, respectively). Inputs from the entorhinal cortex onto GCs exhibit activity-dependent long-term plasticity of N-methyl-D-aspartate receptor (NMDAR)-mediated synaptic transmission. However, the properties, underlying mechanisms, and input-specificity of this plasticity remain poorly understood. Here, we examined NMDAR plasticity rules at MPP-GC and LPP-GC synapses using physiologically relevant stimulation patterns in acute hippocampal slices from rats and mice. Unlike MPP-GC synapses, LPP-GC synapses did not express homosynaptic NMDAR-LTP. Additionally, inducing NMDAR-LTP at MPP-GC synapses potentiated NMDAR transmission at distal LPP-GC synapses. The same stimulation protocol induced homosynaptic α-amino-3-hydroxy-5-methyl-4-isoxazolepropionic acid receptor (AMPAR)-LTP at MPP-GC synapses but heterosynaptic AMPAR-LTD at distal LPP synapses, indicating that NMDAR and AMPAR plasticity are controlled by different plasticity rules. Notably, heterosynaptic but not homosynaptic NMDAR-LTP required Ca²⁺ release from intracellular, ryanodine receptor-dependent Ca²⁺ stores. Lastly, genetic deletion of the GluN2D subunit from GCs or selective antagonism of GluN2D-containing NMDARs abolished heterosynaptic LTP. Heterosynaptic NMDAR-mediated LTP may have important consequences for the dendritic integration of functionally distinct excitatory inputs by dentate granule cells.</p>","PeriodicalId":12650,"journal":{"name":"Frontiers in Synaptic Neuroscience","volume":"18 ","pages":"1825949"},"PeriodicalIF":6.9,"publicationDate":"2026-07-22","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC13437645/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"148678287","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":"Correction: Automated ROI detection allows rapid quantification of synaptic activity across tens of thousands of synapses in cell culture.","authors":"John Carl Begley, Harald Prüss, Paul Turko, Camin Dean","doi":"10.3389/fnsyn.2026.1904571","DOIUrl":"https://doi.org/10.3389/fnsyn.2026.1904571","url":null,"abstract":"<p><p>[This corrects the article DOI: 10.3389/fnsyn.2026.1832103.].</p>","PeriodicalId":12650,"journal":{"name":"Frontiers in Synaptic Neuroscience","volume":"18 ","pages":"1904571"},"PeriodicalIF":6.9,"publicationDate":"2026-07-20","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC13430714/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"148669314","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}